4.6

CiteScore

2.2

Impact Factor
  • ISSN 1674-8301
  • CN 32-1810/R
Volume 38 Issue 1
Jan.  2024
Turn off MathJax
Article Contents
Abstract
Acknowledgments
Funding
References
Alexey N. Inyushkin, Vitalii S. Poletaev, Elena M. Inyushkina, Igor S. Kalberdin, Andrey A. Inyushkin. Irisin/BDNF signaling in the muscle-brain axis and circadian system: A review[J]. The Journal of Biomedical Research, 2024, 38(1): 1-16. DOI: 10.7555/JBR.37.20230133
Citation: Alexey N. Inyushkin, Vitalii S. Poletaev, Elena M. Inyushkina, Igor S. Kalberdin, Andrey A. Inyushkin. Irisin/BDNF signaling in the muscle-brain axis and circadian system: A review[J]. The Journal of Biomedical Research, 2024, 38(1): 1-16. DOI: 10.7555/JBR.37.20230133
shu

Irisin/BDNF signaling in the muscle-brain axis and circadian system: A review

  • Department of Human & Animal Physiology, Samara National Research University, Samara 443011, Russia

More Information
  • Corresponding author:

    Alexey N. Inyushkin, Department of Human & Animal Physiology, Samara National Research University, 1 Acad. Pavlova Str., Samara 443011, Russia. E-mail: ainyushkin@mail.ru

  • Received Date: June 03, 2023
  • Revised Date: September 18, 2023
  • Accepted Date: September 24, 2023
  • Available Online: September 27, 2023
  • Published Date: December 27, 2023
    Graphical Abstract
    • Abstract

  • In mammals, the timing of physiological, biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms. To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm, environmental zeitgebers are used by the circadian system. This is done primarily by signals from the retina via the retinohypothalamic tract, but other cues like exercise, feeding, temperature, anxiety, and social events have also been shown to act as non-photic zeitgebers. The recently identified myokine irisin is proposed to serve as an entraining non-photic signal of exercise. Irisin is a product of cleavage and modification from its precursor membrane fibronectin type Ⅲ domain-containing protein 5 (FNDC5) in response to exercise. Apart from well-known peripheral effects, such as inducing the "browning" of white adipocytes, irisin can penetrate the blood-brain barrier and display the effects on the brain. Experimental data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain functions. In several brain areas, irisin induces the production of brain-derived neurotrophic factor (BDNF). In the master clock, a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is suggested. However, the brain receptor for irisin remains unknown. In the current review, the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.

    • FullText(HTML)

  • Dear Editor,

    Cardiovascular disease is the leading cause of deaths worldwide, with coronary artery disease (CAD) accounting for approximately 50% of its mortality. Dual antiplatelet therapy, including aspirin and a P2Y12 inhibitor, is the most important treatment for CAD patients undergoing percutaneous coronary intervention (PCI) to prevent recurrent ischemic events and cardiac death. Clopidogrel is one of the commonly used P2Y12 inhibitors. However, up to 30% of patients treated with a standard dose of clopidogrel present with high on-treatment platelet reactivity (HOPR), which is associated with the increased ischemic risks[1]. The causes of HOPR are multifactorial and complex. Polymorphisms of cytochrome P450 enzyme genes (such as CYP2C19) have been widely reported to influence platelet response to clopidogrel[2], which, however, may account for only 12% of HOPR[2]. The etiology for the rest of the patients exhibiting HOPR remains uncertain, which is a residual ischemic risk for CAD patients who are taking clopidogrel. The present study aims to investigate risk factors associated with HOPR in CAD patients undergoing PCI and receiving the dual antiplatelet therapy with aspirin and clopidogrel. The present study is a cross-sectional cohort study performed in the First Affiliated Hospital of Nanjing Medical University using our pre-registered database (Unique Identifier: NCT01968499), complied with the Helsinki declaration and local regulations, and was approved by the Institutional Review Board of the First Affiliated Hospital of Nanjing Medical University (No. 2011-SRFA-099). A written informed consent was obtained from each patient.

    CAD patients who had undergone PCI and taken clopidogrel (75 mg/day) combined with aspirin (100 mg/day) for more than five days were consecutively enrolled between April 2011 and October 2016 in the coronary care unit of the First Affiliated Hospital of Nanjing Medical University. We excluded patients who were: (1) intolerant to aspirin or clopidogrel; (2) with hematological diseases; (3) with baseline hemoglobin < 90 g/L, or platelet count < 80 × 109/L or > 450 × 109/L; (4) taking other antiplatelet agents or anticoagulants or any drugs that could potentially interfere with the antiplatelet efficacy of the study drugs; and (5) with end-stage diseases (e.g., cancer) or other conditions that were inappropriate to be recruited at the discretion of the investigators. The patients' demographics, present disease history, past disease history, personal history, physical examination, laboratory examination, and medications were recorded. In addition, venous blood was collected into two 2.7 mL vacutainer tubes containing 3.2% sodium citrate two hours after the patients took clopidogrel and aspirin. Platelet reactivities were measured by the light transmission aggregometry within two hours of the sampling. Platelet-rich plasma (PRP) was separated by centrifuging the blood sample at 200 g at 22 ℃ for 5 min, and platelet poor plasma (PPP) was obtained by spinning the remaining blood at 2465 g for another 10 min. Platelet counts were adjusted by adding PPP to PRP to achieve a count of 250 × 109/L. A total of 500 μL adjusted PRP was tested by a Chronolog aggregometer (Model 700, Chrono-log Corporation, Havertown, PA, USA) with 500 μL PPP as control. Platelet aggregation was induced by 2.5 μL adenosine diphosphate (ADP) with a final concentration of 5 μmol/L or 10 μL arachidonic acid (AA) with a final concentration of 1 mmol/L, and recorded as PLADP or PLAA, respectively. HOPR was defined as PLADP > 40%[3].

    SPSS version 25.0 (SPSS, Inc., Chicago, IL, USA) was used for statistical analysis. Continuous variables were presented as mean ± standard deviation, and categorical variables were expressed as frequencies or percentages. The independent Student's t-test or Chi-square test was used as appropriate to assess differences between the HOPR and non-HOPR groups, and the variables that were significantly different between the two groups were included in the logistic regression analysis to identify the factors associated with the HOPR. Covariates with P-values less than 0.05 in univariable regression analysis were selected for the inclusion in the multiple logistic regression model. A two-tailed P-value < 0.05 was considered statistically significant for all the tests.

    As a result, 1649 eligible patients were included in the analyses. By in platelet reactivity assessment, HOPR was observed in 389 (23.6%) patients. The baseline characteristics of patients are listed in Table 1.

    Table  1.  Baseline characteristics of patients with or without HOPR
    VariablesHOPR Non-HOPRP-value
    N[n (%)] or (mean±SD) N[n (%)] or (mean±SD)
    Female 389 117 (30.1) 1260 294 (23.3) 0.007
    Age (years) 389 64.4±10.3 1260 63.6±10.5 0.201
    BMI (kg/m2) 373 25.0±3.0 1182 24.6±3.1 0.023
    Smoking 387 160 (41.3) 1251 600 (48.0) 0.023
    Drinking 386 80 (20.7) 1248 314 (25.2) 0.075
    Hypertension 388 260 (67.0) 1258 831 (66.1) 0.728
    Diabetes mellitus 387 100 (25.8) 1253 331 (26.4) 0.822
    Hyperlipidemia 330 33 (10.0) 852 81 (9.5) 0.797
    PCI history 385 25 (6.5) 1249 127 (10.2) 0.030
    RBC (1012/L) 384 4.4±0.5 1237 4.5±0.6 0.010
    Hemoglobin (g/L) 384 134.1±15.3 1238 135.8±17.7 0.100
    WBC (109/L) 384 7.4±3.0 1238 6.9±2.4 0.004
    Neutrophil ratio (%) 384 64.0±11.8 1236 63.4±10.1 0.398
    Platelet (109/L) 384 189.2±56.4 1238 195.2±63.4 0.094
    ALT (U/L) 380 37.5±34.8 1242 36.3±50.3 0.660
    LDH (U/L) 374 310.0±338.9 1216 265.1±255.9 0.018
    γ-GGT (U/L) 344 44.2±65.0 1192 47.2±93.4 0.585
    TBIL (µmol/L) 346 13.3±6.1 1200 13.6±24.9 0.849
    DBIL (µmol/L) 345 4.2±2.1 1194 6.5±62.7 0.504
    IBIL (µmol/L) 345 9.1±4.4 1189 8.6±4.5 0.087
    BUN (mmol/L) 380 6.0±3.7 1238 8.0±41.1 0.347
    Creatinine (µmol/L) 380 77.9±22.0 1240 80.7±40.8 0.209
    Uric acid (µmol/L) 374 332.1±99.0 1221 346.1±93.8 0.013
    FBG (mmol/L) 370 6.3±2.2 1194 6.0±2.0 0.027
    HbA1c (%) 135 6.8±1.7 411 6.8±1.5 0.567
    TC (mmol/l) 373 4.3±1.2 1221 4.3±2.1 0.911
    TG (mmol/L) 374 1.6±0.9 1222 1.9±5.9 0.325
    LDL-C (mmol/L) 374 2.6±0.9 1220 3.4±12.1 0.231
    HDL-C (mmol/L) 374 1.1±0.3 1220 1.3±5.5 0.569
    Lp(a) (mg/L) 367 280.4±249.7 1210 282.7±267.2 0.883
    CK-MB (ng/mL) 312 39.1±79.1 968 36.4±138.7 0.750
    PCT (ng/mL) 135 0.4±1.3 370 1.0±2.8 < 0.001
    CRP (mg/L) 82 8.8±19.9 241 7.3±18.9 0.551
    PT (s) 332 11.9±1.2 1163 11.9±1.4 0.578
    APTT (s) 329 48.2±394.5 1160 26.7±9.9 0.323
    INR 332 1.4±3.1 1160 1.1±1.7 0.129
    PLADP (%) 389 50.4±7.7 1260 24.5±9.4 < 0.001
    PLAA (%) 389 5.2±9.8 1260 4.0±4.6 0.017
    PPIs 389 72 (18.5) 1260 233 (18.5) 0.994
    Statins 389 367 (94.3) 1260 1128 (89.5) 0.004
    CCBs 389 136 (35.0) 1260 413 (32.8) 0.424
    Diagnoses 377 1234 0.033
    　SA 69 69 (18.3) 305 305 (24.7)
    　UA 187 187 (49.6) 605 605 (49.0)
    　NSTEMI 34 34 (9.0) 88 88 (7.2)
    　STEMI 87 87 (23.1) 236 236 (19.1)
    Abbreviations: HOPR, high on-treatment platelet reactivity; BMI, body mass index; PCI, percutaneous coronary intervention; RBC, red blood cell; WBC, white blood cell; ALT, alanine transaminase; LDH, lactate dehydrogenase; γ-GGT, gamma-glutamyl transpeptidase; TBIL, total bilirubin; DBIL, direct bilirubin; IBIL, indirect bilirubin; BUN, blood urea nitrogen; FBG, fasting blood glucose; HbA1c, hemoglobin A1c; TC, total cholesterol; TG, total triglyceride; LDL, low density lipoprotein; HDL, high density lipoprotein; Lp(a), lipoprotein (a); CK-MB, creatine kinase-MB; PCT, procalcitonin; CRP, C-reactive protein; PT, prothrombin time; APTT, activated partial thromboplastin time; INR, international normalized ratio; PLADP, platelet aggregation induced by adenosine diphosphate; PLAA, platelet aggregation induced by arachidonic acid; PPIs, proton pump inhibitors; CCBs, calcium channel blockers; SA, stable angina; UA, unstable angina; NSTEMI, non-ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction; SD, standard deviation.
     | Show Table
    DownLoad: CSV

    Female, body mass index (BMI), smoking, PCI history, red blood cell (RBC) counts, white blood cell counts, lactate dehydrogenase, uric acid, fasting blood glucose, procalcitonin, PLAA, statin consumption, and CAD diagnosis were significantly associated with HOPR in the univariable logistic regression analyses (all P < 0.05) (Table 2). However, multivariable logistic regression analysis showed that only RBC count, BMI, and statin consumption were independently associated with HOPR (OR = 0.480, 95% CI: 0.302–0.763, P = 0.002; OR = 1.140, 95% CI: 1.054–1.232, P = 0.001; OR = 4.504, 95% CI: 1.004–20.208, P = 0.049, respectively) (Table 2).

    Table  2.  Logistic regression analysis for HOPR
    VariablesnUnivariate logistic regressionMultivariate logistic regression
    OR (95% CI)P-valueOR (95% CI)P-value
    Female vs. male 389 (117/272) 1.413 (1.097–1.820) 0.007
    BMIa 373 1.044 (1.006–1.084) 0.023 1.140 (1.054–1.232) 0.001
    Smoking vs. no smoking 387 (160/227) 0.765 (0.607–0.963) 0.023
    PCI history vs. no PCI history 385 (25/360) 0.614 (0.393–0.957) 0.031
    RBCa 384 0.757 (0.613–0.934) 0.010 0.480 (0.302–0.763) 0.002
    WBCa 384 1.070 (1.026–1.116) 0.002
    LDHa 374 1.001 (1.000–1.001) 0.007
    Uric acida 374 0.998 (0.997–1.000) 0.013
    FBGa 370 1.062 (1.009–1.119) 0.023
    PCTa 135 0.848 (0.736–0.977) 0.022
    Statins vs. no statins 389 (367/22) 1.952 (1.224–3.112) 0.005 4.504 (1.004–20.208) 0.049
    SA 69 1 –
    UA vs. SA 187/69 1.366 (1.004–1.860) 0.047
    NSTEMI vs. SA 34/69 1.708 (1.063–2.744) 0.027
    STEMI vs. SA 87/69 1.630 (1.138–2.333) 0.008
    aThe ORs for the continuous variables indicate that 1-unit increase of the variables is associated with a [(OR-1)×100] % increased risk of HOPR.Abbreviations: HOPR, high on-treatment platelet reactivity; OR, odds ratio; CI, confidence interval; BMI, body mass index; PCI, percutaneous coronary intervention; RBC, red blood cell; WBC, white blood cell; LDH, lactate dehydrogenase; FBG, fasting blood glucose; PCT, procalcitonin; SA, stable angina; UA, unstable angina; NSTEMI, non-ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction.
     | Show Table
    DownLoad: CSV

    This is the first study to show that in CAD patients undergoing PCI and treated with clopidogrel, the RBC counts were independently and negatively associated with HOPR. Karolczak et al[4] also reported a negative association between RBC counts and PLADP; however, their results were based on 251 volunteers without acute coronary syndrome, and the platelet activity was measured by multiplate impedance aggregometry. In contrast, the present study recruited a large number of CAD patients, adopted the gold standard light transmission aggregometry method, and was the first to reveal a negative association between RBC counts with HOPR.

    The effects of RBC on platelet aggregation may be mediated by ADP and nitric oxide (NO). ADP is stored in RBC and promotes platelet aggregation by binding to the P2Y12 receptor on the platelet surface, further activating glycoprotein (GP) Ⅱb/Ⅲa[4]. By contrast, NO, produced in the membrane and cytoplasm of RBC by the endothelial-type nitric oxide synthase (eNOS)[4], has been reported to inhibit the activation of GP Ⅱb/Ⅲa and platelet aggregation via the increase of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP)[5]. One study demonstrated that during platelet aggregation, the inhibitory effect of NO predominated over the activating effect of ADP[4]. In addition, studies have confirmed that RBC plays an important role in maintaining cardiovascular homeostasis and vascular function[6]. RBC is responsible for the synthesis and release of NO via the release of adenosine triphosphate (ATP) to activate the endothelial purinergic receptors[6]. ATP is degraded to ADP and adenosine by nucleotidases. Both ATP and ADP are present in approximately equal amount in platelet granules, while RBC releases 10 times more ATP than ADP[7]. Moreover, RBC is involved not only in the ATP release, but also in regulating adenosine uptake. Therefore, we hypothesize that patients with higher RBC counts produce more NO and ATP, which causes a stronger inhibition of platelet aggregation and a less likelihood of HOPR. However, future studies are needed to clarify the mechanism of this association between RBC counts and HOPR.

    Our results were also consistent with the reports indicating that BMI and statin consumption were independent risk factors for HOPR[8–9]. These may be explained by a decreased activity of CYP3A4 (a clopidogrel-related metabolic enzyme) and a relatively insufficient dose of clopidogrel in obese patients[9]. Most lipophilic statins, such as simvastatin and atorvastatin, are metabolized by the cytochrome P450 enzyme (mainly by CYP3A4) and competitively inhibit the metabolic activation of clopidogrel[8]. Thus, weight control is necessary for obese patients with CAD to reduce their risk of HOPR. Besides, lipid-lowering drugs that are less metabolized by CYP3A4 (e.g., rosuvastatin) may be more suitable for patients with HOPR. Several clinical variables, such as WBC counts and procalcitonin, were reported to be associated with platelet reactivity[10], but these associations were not confirmed in the present study. These may be explained by the biases from sample selection, sample size, differences in the detection methods, or different races of the study populations.

    The present study has some potential limitations. Although there were independent correlations of RBC counts, BMI and statins consumption with HOPR, the differences between groups (patients with or without high platelet reactivity) were subtle. The clinical value of the observations needs to be further explored in future clinical trials.

    In conclusion, the present study has revealed that low RBC counts, high BMI, and statin consumption may independently predict HOPR in CAD patients undergoing PCI and treated with clopidogrel.

    The present study was supported by the National Natural Science Foundation of China (Grant No. 82170351), the Jiangsu Province's Key Provincial Talents Program (Grant No. ZDRCA2016013), and the Special Fund for Key R&D Plans (Social Development) of Jiangsu Province (Grant No. BE2019754).

    Yours Sincerely,Qian Gu△, Qin Wang△, Rui Hua△, Wenhao Zhang, Jianzhen Teng, Jiazheng Ma, Zhou Dong, Xiaoxuan Gong✉, Chunjian Li✉ Department of Cardiology,the First Affiliated Hospital of Nanjing Medical University,Nanjing, Jiangsu 210029,China.△These authors contributed equally to this work.✉Chunjian Li and Xiaoxuan Gong. E-mails: lijay@njmu.edu.cn (Li) and xiaoxuangong@sina.com (Gong).

    None.

    The study was supported by the Russian Science Foundation (Grant No. 23-25-00152).

    CLC number: R741, Document code: A

    The authors reported no conflict of interests.

    • References (138)
  • [1]
    Legård GE, Pedersen BK. Muscle as an endocrine organ[M]//Zoladz JA. Muscle and Exercise Physiology. London: Academic Press, 2019: 285–307.
    [2]
    Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis[J]. Nature, 2012, 481(7382): 463–468. doi: 10.1038/nature10777
    [3]
    Wu J, Boström P, Sparks LM, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human[J]. Cell, 2012, 150(2): 366–376. doi: 10.1016/j.cell.2012.05.016
    [4]
    Wrann CD, White JP, Salogiannnis J, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway[J]. Cell Metab, 2013, 18(5): 649–659. doi: 10.1016/j.cmet.2013.09.008
    [5]
    Wrann CD. FNDC5/Irisin - their role in the nervous system and as a mediator for beneficial effects of exercise on the brain[J]. Brain Plast, 2015, 1(1): 55–61. doi: 10.3233/BPL-150019
    [6]
    Hastings MH, Maywood ES, Reddy AB. Two decades of circadian time[J]. J Neuroendocrinol, 2008, 20(6): 812–819. doi: 10.1111/j.1365-2826.2008.01715.x
    [7]
    Zhang R, Lahens NF, Ballance HI, et al. A circadian gene expression atlas in mammals: implications for biology and medicine[J]. Proc Natl Acad Sci U S A, 2014, 111(45): 16219–16224. doi: 10.1073/pnas.1408886111
    [8]
    Mure LS, Le HD, Benegiamo G, et al. Diurnal transcriptome atlas of a primate across major neural and peripheral tissues[J]. Science, 2018, 359(6381): eaao0318. doi: 10.1126/science.aao0318
    [9]
    Aton SJ, Herzog ED. Come together, right..now: synchronization of rhythms in a mammalian circadian clock[J]. Neuron, 2005, 48(4): 531–534. doi: 10.1016/j.neuron.2005.11.001
    [10]
    Eastman CI, Suh C, Tomaka VA, et al. Circadian rhythm phase shifts and endogenous free-running circadian period differ between African-Americans and European-Americans[J]. Sci Rep, 2015, 5: 8381. doi: 10.1038/srep08381
    [11]
    Tahara Y, Aoyama S, Shibata S. The mammalian circadian clock and its entrainment by stress and exercise[J]. J Physiol Sci, 2017, 67(1): 1–10. doi: 10.1007/s12576-016-0450-7
    [12]
    Liu C, Li S, Liu T, et al. Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism[J]. Nature, 2007, 447(7143): 477–481. doi: 10.1038/nature05767
    [13]
    Welsh DK, Takahashi JS, Kay SA. Suprachiasmatic nucleus: cell autonomy and network properties[J]. Annu Rev Physiol, 2010, 72: 551–577. doi: 10.1146/annurev-physiol-021909-135919
    [14]
    Harfmann BD, Schroder EA, Esser KA. Circadian rhythms, the molecular clock, and skeletal muscle[J]. J Biol Rhythms, 2015, 30(2): 84–94. doi: 10.1177/0748730414561638
    [15]
    Tahara Y, Shibata S. Entrainment of the mouse circadian clock: effects of stress, exercise, and nutrition[J]. Free Radic Biol Med, 2018, 119: 129–138. doi: 10.1016/j.freeradbiomed.2017.12.026
    [16]
    Miyazaki M, Schroder E, Edelmann SE, et al. Age-associated disruption of molecular clock expression in skeletal muscle of the spontaneously hypertensive rat[J]. PLoS One, 2011, 6(11): e27168. doi: 10.1371/journal.pone.0027168
    [17]
    Higashida K, Kim SH, Jung SR, et al. Effects of resveratrol and SIRT1 on PGC-1α activity and mitochondrial biogenesis: a reevaluation[J]. PLoS Biol, 2013, 11(7): e1001603. doi: 10.1371/journal.pbio.1001603
    [18]
    Puigserver P, Wu Z, Park CW, et al. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis[J]. Cell, 1998, 92(6): 829–839. doi: 10.1016/S0092-8674(00)81410-5
    [19]
    Ryan MT, Hoogenraad NJ. Mitochondrial-nuclear communications[J]. Annu Rev Biochem, 2007, 76: 701–722. doi: 10.1146/annurev.biochem.76.052305.091720
    [20]
    Nakahata Y, Kaluzova M, Grimaldi B, et al. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control[J]. Cell, 2008, 134(2): 329–340. doi: 10.1016/j.cell.2008.07.002
    [21]
    Chang HC, Guarente L. SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging[J]. Cell, 2013, 153(7): 1448–1460. doi: 10.1016/j.cell.2013.05.027
    [22]
    Ashton A, Foster RG, Jagannath A. Photic entrainment of the circadian system[J]. Int J Mol Sci, 2022, 23(2): 729. doi: 10.3390/ijms23020729
    [23]
    Hannibal J. Comparative neurology of circadian photoreception: the retinohypothalamic tract (RHT) in sighted and naturally blind mammals[J]. Front Neurosci, 2021, 15: 640113. doi: 10.3389/fnins.2021.640113
    [24]
    Michel S, Colwell CS. Cellular communication and coupling within the suprachiasmatic nucleus[J]. Chronobiol Int, 2001, 18(4): 579–600. doi: 10.1081/CBI-100106074
    [25]
    Grone BP, Chang D, Bourgin P, et al. Acute light exposure suppresses circadian rhythms in clock gene expression[J]. J Biol Rhythms, 2011, 26(1): 78–81. doi: 10.1177/0748730410388404
    [26]
    Mendoza JY, Dardente H, Escobar C, et al. Dark pulse resetting of the suprachiasmatic clock in Syrian hamsters: behavioral phase-shifts and clock gene expression[J]. Neuroscience, 2004, 127(2): 529–537. doi: 10.1016/j.neuroscience.2004.05.026
    [27]
    Richardson CE, Gradisar M, Short MA, et al. Can exercise regulate the circadian system of adolescents? Novel implications for the treatment of delayed sleep-wake phase disorder[J]. Sleep Med Rev, 2017, 34: 122–129. doi: 10.1016/j.smrv.2016.06.010
    [28]
    Sen S, Raingard H, Dumont S, et al. Ultradian feeding in mice not only affects the peripheral clock in the liver, but also the master clock in the brain[J]. Chronobiol Int, 2017, 34(1): 17–36. doi: 10.1080/07420528.2016.1231689
    [29]
    Wams EJ, Riede SJ, van der Laan I, et al. Mechanisms of non-photic entrainment[M]//Kumar V. Biological Timekeeping: Clocks, Rhythms and Behaviour. New Delhi: Springer, 2017: 395–404.
    [30]
    Reebs SG, Mrosovsky N. Effects of induced wheel running on the circadian activity rhythms of Syrian hamsters: entrainment and phase response curve[J]. J Biol Rhythms, 1989, 4(1): 39–48. doi: 10.1177/074873048900400103
    [31]
    van Oosterhout F, Lucassen EA, Houben T, et al. Amplitude of the SCN clock enhanced by the behavioral activity rhythm[J]. PLoS One, 2012, 7(6): e39693. doi: 10.1371/journal.pone.0039693
    [32]
    Saderi N, Cazarez-Márquez F, Buijs FN, et al. The NPY intergeniculate leaflet projections to the suprachiasmatic nucleus transmit metabolic conditions[J]. Neuroscience, 2013, 246: 291–300. doi: 10.1016/j.neuroscience.2013.05.004
    [33]
    Inyushkin AN, Petrova AA, Tkacheva MA, et al. Effects of neuropeptide Y on neuron spike activity in the rat suprachiasmatic nucleus in vitro[J]. Neurosci Behav Physiol, 2017, 47(3): 337–344. doi: 10.1007/s11055-017-0402-6
    [34]
    Melancon MO, Lorrain D, Dionne IJ. Exercise and sleep in aging: emphasis on serotonin[J]. Pathol Biol, 2014, 62(5): 276–283. doi: 10.1016/j.patbio.2014.07.004
    [35]
    Richards J, Gumz ML. Advances in understanding the peripheral circadian clocks[J]. FASEB J, 2012, 26(9): 3602–3613. doi: 10.1096/fj.12-203554
    [36]
    Yamazaki S, Numano R, Abe M, et al. Resetting central and peripheral circadian oscillators in transgenic rats[J]. Science, 2000, 288(5466): 682–685. doi: 10.1126/science.288.5466.682
    [37]
    Schiaffino S, Blaauw B, Dyar KA. The functional significance of the skeletal muscle clock: lessons from Bmal1 knockout models[J]. Skelet Muscle, 2016, 6: 33. doi: 10.1186/s13395-016-0107-5
    [38]
    Schroder EA, Esser KA. Circadian rhythms, skeletal muscle molecular clocks, and exercise[J]. Exerc Sport Sci Rev, 2013, 41(4): 224–229. doi: 10.1097/JES.0b013e3182a58a70
    [39]
    Hodge BA, Wen Y, Riley LA, et al. The endogenous molecular clock orchestrates the temporal separation of substrate metabolism in skeletal muscle[J]. Skelet Muscle, 2015, 5: 17. doi: 10.1186/s13395-015-0039-5
    [40]
    Pizarro A, Hayer K, Lahens NF, et al. CircaDB: a database of mammalian circadian gene expression profiles[J]. Nucleic Acids Res, 2013, 41(D1): D1009–D1013. doi: 10.1093/nar/gks1161
    [41]
    Riley LA, Esser KA. The role of the molecular clock in skeletal muscle and what it is teaching us about muscle-bone crosstalk[J]. Curr Osteoporos Rep, 2017, 15(3): 222–230. doi: 10.1007/s11914-017-0363-2
    [42]
    Maak S, Norheim F, Drevon CA, et al. Progress and challenges in the biology of FNDC5 and irisin[J]. Endocr Rev, 2021, 42(4): 436–456. doi: 10.1210/endrev/bnab003
    [43]
    Roca-Rivada A, Castelao C, Senin LL, et al. FNDC5/irisin is not only a myokine but also an adipokine[J]. PLoS One, 2013, 8(4): e60563. doi: 10.1371/journal.pone.0060563
    [44]
    Huh JY. The role of exercise-induced myokines in regulating metabolism[J]. Arch Pharm Res, 2018, 41(1): 14–29. doi: 10.1007/s12272-017-0994-y
    [45]
    Mattson MP, Moehl K, Ghena N, et al. Intermittent metabolic switching, neuroplasticity and brain health[J]. Nat Rev Neurosci, 2018, 19(2): 63–80. https://www.nstl.gov.cn/paper_detail.html?id=ef87d2288e906ac1a09d969b0229074f
    [46]
    Handschin C, Spiegelman BM. The role of exercise and PGC1α in inflammation and chronic disease[J]. Nature, 2008, 454(7203): 463–469. doi: 10.1038/nature07206
    [47]
    Lecker SH, Zavin A, Cao P, et al. Expression of the irisin precursor FNDC5 in skeletal muscle correlates with aerobic exercise performance in patients with heart failure[J]. Circ Heart Fail, 2012, 5(6): 812–818. doi: 10.1161/CIRCHEARTFAILURE.112.969543
    [48]
    Zhang W, Chang L, Zhang C, et al. Irisin: a myokine with locomotor activity[J]. Neurosci Lett, 2015, 595: 7–11. doi: 10.1016/j.neulet.2015.03.069
    [49]
    Zhang Y, Li R, Meng Y, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling[J]. Diabetes, 2014, 63(2): 514–525. doi: 10.2337/db13-1106
    [50]
    Phillips C, Baktir MA, Srivatsan M, et al. Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling[J]. Front Cell Neurosci, 2014, 8: 170. doi: 10.3389/fncel.2014.00170
    [51]
    Jodeiri Farshbaf M, Alviña K. Multiple roles in neuroprotection for the exercise derived myokine Irisin[J]. Front Aging Neurosci, 2021, 13: 649929. doi: 10.3389/fnagi.2021.649929
    [52]
    Piya MK, Harte AL, Sivakumar K, et al. The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes[J]. Am J Physiol Endocrinol Metab, 2014, 306(5): E512–E518. doi: 10.1152/ajpendo.00308.2013
    [53]
    Jodeiri Farshbaf M, Ghaedi K, Megraw TL, et al. Does PGC1α/FNDC5/BDNF elicit the beneficial effects of exercise on neurodegenerative disorders?[J]. Neuromolecular Med, 2016, 18(1): 1–15. doi: 10.1007/s12017-015-8370-x
    [54]
    Steiner JL, Murphy EA, McClellan JL, et al. Exercise training increases mitochondrial biogenesis in the brain[J]. J Appl Physiol, 2011, 111(4): 1066–1071. doi: 10.1152/japplphysiol.00343.2011
    [55]
    Cheng A, Wan R, Yang JL, et al. Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines[J]. Nat Commun, 2012, 3: 1250. doi: 10.1038/ncomms2238
    [56]
    Zsuga J, More CE, Erdei T, et al. Blind spot for sedentarism: redefining the diseasome of physical inactivity in view of circadian system and the irisin/BDNF axis[J]. Front Neurol, 2018, 9: 818. doi: 10.3389/fneur.2018.00818
    [57]
    Dibner C, Schibler U, Albrecht U. The mammalian circadian timing system: organization and coordination of central and peripheral clocks[J]. Annu Rev Physiol, 2010, 72: 517–549. doi: 10.1146/annurev-physiol-021909-135821
    [58]
    Marchant EG, Mistlberger RE. Entrainment and phase shifting of circadian rhythms in mice by forced treadmill running[J]. Physiol Behav, 1996, 60(2): 657–663. doi: 10.1016/S0031-9384(96)80045-X
    [59]
    Schroeder AM, Truong D, Loh DH, et al. Voluntary scheduled exercise alters diurnal rhythms of behaviour, physiology and gene expression in wild-type and vasoactive intestinal peptide-deficient mice[J]. J Physiol, 2012, 590(23): 6213–6226. doi: 10.1113/jphysiol.2012.233676
    [60]
    Hughes ATL, Samuels RE, Baño-Otálora B, et al. Timed daily exercise remodels circadian rhythms in mice[J]. Commun Biol, 2021, 4(1): 761. doi: 10.1038/s42003-021-02239-2
    [61]
    Ehlen JC, Brager AJ, Baggs J, et al. Bmal1 function in skeletal muscle regulates sleep[J]. eLife, 2017, 6: e26557. doi: 10.7554/eLife.26557
    [62]
    Weinert D, Weiß T. A nonlinear interrelationship between period length and the amount of activity—Age-dependent changes[J]. Biol Rhythm Res, 1997, 28(1): 105–120. doi: 10.1076/brhm.28.1.105.12983
    [63]
    Weinert D, Schottner K. An inbred lineage of Djungarian hamsters with a strongly attenuated ability to synchronize[J]. Chronobiol Int, 2007, 24(6): 1065–1079. doi: 10.1080/07420520701791588
    [64]
    Antle MC, Sterniczuk R, Smith VM, et al. Non-photic modulation of phase shifts to long light pulses[J]. J Biol Rhythms, 2007, 22(6): 524–533. doi: 10.1177/0748730407306882
    [65]
    Steinlechner S, Stieglitz A, Ruf T. Djungarian hamsters: a species with a labile circadian pacemaker? Arrhythmicity under a light-dark cycle induced by short light pulses[J]. J Biol Rhythms, 2002, 17(3): 248–258. doi: 10.1177/074873040201700308
    [66]
    Mrosovsky N. Locomotor activity and non-photic influences on circadian clocks[J]. Biol Rev, 1996, 71(3): 343–372. doi: 10.1111/j.1469-185X.1996.tb01278.x
    [67]
    Youngstedt SD, Elliott JA, Kripke DF. Human circadian phase-response curves for exercise[J]. J Physiol, 2019, 597(8): 2253–2268. doi: 10.1113/JP276943
    [68]
    Buxton OM, Lee CW, L'Hermite-Balériaux M, et al. Exercise elicits phase shifts and acute alterations of melatonin that vary with circadian phase[J]. Am J Physiol Regul Integr Comp Physiol, 2003, 284(3): R714–R724. doi: 10.1152/ajpregu.00355.2002
    [69]
    Buxton OM, Frank SA, L'Hermite-Balériaux M, et al. Roles of intensity and duration of nocturnal exercise in causing phase delays of human circadian rhythms[J]. Am J Physiol, 1997, 273(3): E536–E542. doi: 10.1152/ajpendo.1997.273.3.E536
    [70]
    Yamanaka Y, Hashimoto S, Tanahashi Y, et al. Physical exercise accelerates reentrainment of human sleep-wake cycle but not of plasma melatonin rhythm to 8-h phase-advanced sleep schedule[J]. Am J Physiol Regul Integr Comp Physiol, 2010, 298(3): R681–R691. doi: 10.1152/ajpregu.00345.2009
    [71]
    Lang C, Richardson C, Short MA, et al. Low-intensity scheduled morning exercise for adolescents with a late chronotype: a novel treatment to advance circadian phase?[J]. Sleep Adv, 2022, 3(1): zpac021. doi: 10.1093/sleepadvances/zpac021
    [72]
    Kalak N, Gerber M, Kirov R, et al. Daily morning running for 3 weeks improved sleep and psychological functioning in healthy adolescents compared with controls[J]. J Adolesc Health, 2012, 51(6): 615–622. doi: 10.1016/j.jadohealth.2012.02.020
    [73]
    Tilp M, Scharf C, Payer G, et al. Physical exercise during the morning school-break improves basic cognitive functions[J]. Mind Brain Educ, 2020, 14(1): 24–31. doi: 10.1111/mbe.12228
    [74]
    Zhai Q, Zeng Y, Gu Y, et al. Time-restricted feeding entrains long-term behavioral changes through the IGF2-KCC2 pathway[J]. iScience, 2022, 25(5): 104267. doi: 10.1016/j.isci.2022.104267
    [75]
    de Goede P, Wefers J, Brombacher EC, et al. Circadian rhythms in mitochondrial respiration[J]. J Mol Endocrinol, 2018, 60(3): R115–R130. doi: 10.1530/JME-17-0196
    [76]
    Yamanaka Y, Honma S, Honma KI. Two coupled circadian oscillators are involved in nonphotic acceleration of reentrainment to shifted light cycles in mice[J]. J Biol Rhythms, 2018, 33(6): 614–625. doi: 10.1177/0748730418796300
    [77]
    Ortega GJ, Romanelli L, Golombek DA. Statistical and dynamical analysis of circadian rhythms[J]. J Theor Biol, 1994, 169(1): 15–21. doi: 10.1006/jtbi.1994.1126
    [78]
    Leise TL, Harrington ME, Molyneux PC, et al. Voluntary exercise can strengthen the circadian system in aged mice[J]. Age, 2013, 35(6): 2137–2152. doi: 10.1007/s11357-012-9502-y
    [79]
    Weinert D. Age-dependent changes of the circadian system[J]. Chronobiol Int, 2000, 17(3): 261–283. doi: 10.1081/CBI-100101048
    [80]
    Weinert D, Schöttner K, Meinecke AC, et al. Voluntary exercise stabilizes photic entrainment of djungarian hamsters (Phodopus sungorus) with a delayed activity onset[J]. Chronobiol Int, 2018, 35(10): 1435–1444. doi: 10.1080/07420528.2018.1490313
    [81]
    Park TH, Lee HJ, Lee JB. Effect of heat stimulation on circulating irisin in humans[J]. Front Physiol, 2021, 12: 675377. doi: 10.3389/fphys.2021.675377
    [82]
    Herzog ED, Huckfeldt RM. Circadian entrainment to temperature, but not light, in the isolated suprachiasmatic nucleus[J]. J Neurophysiol, 2003, 90(2): 763–770. doi: 10.1152/jn.00129.2003
    [83]
    Saini C, Morf J, Stratmann M, et al. Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators[J]. Genes Dev, 2012, 26(6): 567–580. doi: 10.1101/gad.183251.111
    [84]
    A M, Wales TE, Zhou H, et al. Irisin acts through its integrin receptor in a two-step process involving extracellular Hsp90α[J]. Mol Cell, 2023, 83(11): 1903–1920.e12. doi: 10.1016/j.molcel.2023.05.008
    [85]
    Franco OH, de Laet C, Peeters A, et al. Effects of physical activity on life expectancy with cardiovascular disease[J]. Arch Intern Med, 2005, 165(20): 2355–2360. doi: 10.1001/archinte.165.20.2355
    [86]
    Görgens SW, Eckardt K, Jensen J, et al. Exercise and regulation of adipokine and myokine production[J]. Prog Mol Biol Transl Sci, 2015, 135: 313–336. https://www.sciencedirect.com/science/article/abs/pii/S1877117315001349
    [87]
    Pérez-Martínez P, Mikhailidis DP, Athyros VG, et al. Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation[J]. Nutr Rev, 2017, 75(5): 307–326. doi: 10.1093/nutrit/nux014
    [88]
    Ozemek C, Laddu DR, Lavie CJ, et al. An update on the role of cardiorespiratory fitness, structured exercise and lifestyle physical activity in preventing cardiovascular disease and health risk[J]. Prog Cardiovasc Dis, 2018, 61(5-6): 484–490. doi: 10.1016/j.pcad.2018.11.005
    [89]
    Smith PJ, Blumenthal JA, Hoffman BM, et al. Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials[J]. Psychosom Med, 2010, 72(3): 239–252. doi: 10.1097/PSY.0b013e3181d14633
    [90]
    Pascoe MC, Parker AG. Physical activity and exercise as a universal depression prevention in young people: a narrative review[J]. Early Interv Psychiatry, 2019, 13(4): 733–739. doi: 10.1111/eip.12737
    [91]
    Pedersen BK. Physical activity and muscle-brain crosstalk[J]. Nat Rev Endocrinol, 2019, 15(7): 383–392. doi: 10.1038/s41574-019-0174-x
    [92]
    Vanderlinden J, Boen F, van Uffelen JGZ. Effects of physical activity programs on sleep outcomes in older adults: a systematic review[J]. Int J Behav Nutr Phys Act, 2020, 17(1): 11. doi: 10.1186/s12966-020-0913-3
    [93]
    Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation[J]. Trends Neurosci, 2007, 30(9): 464–472. doi: 10.1016/j.tins.2007.06.011
    [94]
    Norheim F, Raastad T, Thiede B, et al. Proteomic identification of secreted proteins from human skeletal muscle cells and expression in response to strength training[J]. Am J Physiol Endocrinol Metab, 2011, 301(5): E1013–E1021. doi: 10.1152/ajpendo.00326.2011
    [95]
    Moon HY, Becke A, Berron D, et al. Running-induced systemic cathepsin B secretion is associated with memory function[J]. Cell Metab, 2016, 24(2): 332–340. doi: 10.1016/j.cmet.2016.05.025
    [96]
    De la Rosa A, Solana E, Corpas R, et al. Long-term exercise training improves memory in middle-aged men and modulates peripheral levels of BDNF and Cathepsin B[J]. Sci Rep, 2019, 9(1): 3337. doi: 10.1038/s41598-019-40040-8
    [97]
    Ma C, Ding H, Deng Y, et al. Irisin: a new code uncover the relationship of skeletal muscle and cardiovascular health during exercise[J]. Front Physiol, 2021, 12: 620608. doi: 10.3389/fphys.2021.620608
    [98]
    Lourenco MV, Frozza RL, de Freitas GB, et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer's models[J]. Nat Med, 2019, 25(1): 165–175. doi: 10.1038/s41591-018-0275-4
    [99]
    Ruan Q, Zhang L, Ruan J, et al. Detection and quantitation of irisin in human cerebrospinal fluid by tandem mass spectrometry[J]. Peptides, 2018, 103: 60–64. doi: 10.1016/j.peptides.2018.03.013
    [100]
    EI Hayek L, Khalifeh M, Zibara V, et al. Lactate mediates the effects of exercise on learning and memory through SIRT1-dependent activation of hippocampal brain-derived neurotrophic factor (BDNF)[J]. J Neurosci, 2019, 39(13): 2369–2382. doi: 10.1523/jneurosci.1661-18.2019
    [101]
    Kim H, Wrann CD, Jedrychowski M, et al. Irisin mediates effects on bone and fat via αV integrin receptors[J]. Cell, 2018, 175(7): 1756–1768.e17. doi: 10.1016/j.cell.2018.10.025
    [102]
    Bi J, Zhang J, Ren Y, et al. Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor[J]. J Cell Mol Med, 2020, 24(1): 996–1009. doi: 10.1111/jcmm.14811
    [103]
    Oguri Y, Shinoda K, Kim H, et al. CD81 controls beige fat progenitor cell growth and energy balance via FAK signaling[J]. Cell, 2020, 182(3): 563–577.e20. doi: 10.1016/j.cell.2020.06.021
    [104]
    Estell EG, Le PT, Vegting Y, et al. Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo[J]. eLife, 2020, 9: e58172. doi: 10.7554/eLife.58172
    [105]
    Waseem R, Shamsi A, Mohammad T, et al. FNDC5/Irisin: physiology and pathophysiology[J]. Molecules, 2022, 27(3): 1118. doi: 10.3390/molecules27031118
    [106]
    Marosi K, Mattson MP. BDNF mediates adaptive brain and body responses to energetic challenges[J]. Trends Endocrinol Metab, 2014, 25(2): 89–98. doi: 10.1016/j.tem.2013.10.006
    [107]
    Chao MV, Rajagopal R, Lee FS. Neurotrophin signalling in health and disease[J]. Clin Sci (Lond), 2006, 110(2): 167–173. doi: 10.1042/CS20050163
    [108]
    Huang TL, Lee CT, Liu YL. Serum brain-derived neurotrophic factor levels in patients with major depression: effects of antidepressants[J]. J Psychiatr Res, 2008, 42(7): 521–525. doi: 10.1016/j.jpsychires.2007.05.007
    [109]
    Dean C, Liu H, Staudt T, et al. Distinct subsets of Syt-IV/BDNF vesicles are sorted to axons versus dendrites and recruited to synapses by activity[J]. J Neurosci, 2012, 32(16): 5398–5413. doi: 10.1523/JNEUROSCI.4515-11.2012
    [110]
    Yang JL, Lin YT, Chuang PC, et al. BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1[J]. Neuromol Med, 2014, 16(1): 161–174. doi: 10.1007/s12017-013-8270-x
    [111]
    Autry AE, Bambah-Mukku D. The role of brain-derived neurotrophic factor in neural circuit development and function[M]//Rubenstein J, Rakic P, Chen B, et al. Synapse Development and Maturation: Comprehensive Developmental Neuroscience. 2nd ed. London: Academic Press, 2020: 443–466.
    [112]
    Fargali S, Sadahiro M, Jiang C, et al. Role of neurotrophins in the development and function of neural circuits that regulate energy homeostasis[J]. J Mol Neurosci, 2012, 48(3): 654–659. doi: 10.1007/s12031-012-9790-9
    [113]
    Ishikawa C, Li H, Ogura R, et al. Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain[J]. PLoS One, 2017, 12(6): e0177833. doi: 10.1371/journal.pone.0177833
    [114]
    Zsuga J, Biro K, Papp C, et al. The "proactive" model of learning: integrative framework for model-free and model-based reinforcement learning utilizing the associative learning-based proactive brain concept[J]. Behav Neurosci, 2016, 130(1): 6–18. doi: 10.1037/bne0000116
    [115]
    Autry AE. Function of brain-derived neurotrophic factor in the hypothalamus: implications for depression pathology[J]. Front Mol Neurosci, 2022, 15: 1028223. doi: 10.3389/fnmol.2022.1028223
    [116]
    Liang FQ, Sohrabji F, Miranda R, et al. Expression of brain-derived neurotrophic factor and its cognate receptor, TrkB, in the rat suprachiasmatic nucleus[J]. Exp Neurol, 1998, 151(2): 184–193. doi: 10.1006/exnr.1998.6804
    [117]
    Griffin ÉW, Mullally S, Foley C, et al. Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males[J]. Physiol Behav, 2011, 104(5): 934–941. doi: 10.1016/j.physbeh.2011.06.005
    [118]
    Kobilo T, Liu QR, Gandhi K, et al. Running is the neurogenic and neurotrophic stimulus in environmental enrichment[J]. Learn Mem, 2011, 18(9): 605–609. doi: 10.1101/lm.2283011
    [119]
    Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition[J]. Eur J Neurosci, 2004, 20(10): 2580–2590. doi: 10.1111/j.1460-9568.2004.03720.x
    [120]
    Zsuga J, Tajti G, Papp C, et al. FNDC5/irisin, a molecular target for boosting reward-related learning and motivation[J]. Med Hypotheses, 2016, 90: 23–28. doi: 10.1016/j.mehy.2016.02.020
    [121]
    Liang FQ, Walline R, Earnest DJ. Circadian rhythm of brain-derived neurotrophic factor in the rat suprachiasmatic nucleus[J]. Neurosci Lett, 1998, 242(2): 89–92. doi: 10.1016/S0304-3940(98)00062-7
    [122]
    Liang FQ, Allen G, Earnest D. Role of brain-derived neurotrophic factor in the circadian regulation of the suprachiasmatic pacemaker by light[J]. J Neurosci, 2000, 20(8): 2978–2987. doi: 10.1523/JNEUROSCI.20-08-02978.2000
    [123]
    Allen GC, Earnest DJ. Overlap in the distribution of TrkB immunoreactivity and retinohypothalamic tract innervation of the rat suprachiasmatic nucleus[J]. Neurosci Lett, 2005, 376(3): 200–204. doi: 10.1016/j.neulet.2004.11.076
    [124]
    Michel S, Clark JP, Ding JM, et al. Brain-derived neurotrophic factor and neurotrophin receptors modulate glutamate-induced phase shifts of the suprachiasmatic nucleus[J]. Eur J Neurosci, 2006, 24(4): 1109–1116. doi: 10.1111/j.1460-9568.2006.04972.x
    [125]
    Serchov T, Heumann R. Constitutive activation of ras in neurons: implications for the regulation of the mammalian circadian clock[J]. Chronobiol Int, 2006, 23(1-2): 191–200. doi: 10.1080/07420520500521970
    [126]
    Serchov T, Heumann R. Ras activity tunes the period and modulates the entrainment of the suprachiasmatic clock[J]. Front Neurol, 2017, 8: 264. doi: 10.3389/fneur.2017.00264
    [127]
    Girardet C, Lebrun B, Cabirol-Pol MJ, et al. Brain-derived neurotrophic factor/TrkB signaling regulates daily astroglial plasticity in the suprachiasmatic nucleus: electron-microscopic evidence in mouse[J]. Glia, 2013, 61(7): 1172–1177. doi: 10.1002/glia.22509
    [128]
    Kim YI, Choi HJ, Colwell CS. Brain-derived neurotrophic factor regulation of N-methyl-D-aspartate receptor-mediated synaptic currents in suprachiasmatic nucleus neurons[J]. J Neurosci Res, 2006, 84(7): 1512–1520. doi: 10.1002/jnr.21063
    [129]
    Lin SY, Wu K, Levine ES, et al. BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B in cortical and hippocampal postsynaptic densities[J]. Mol Brain Res, 1998, 55(1): 20–27. doi: 10.1016/S0169-328X(97)00349-5
    [130]
    Carmignoto G, Pizzorusso T, Tia S, et al. Brain-derived neurotrophic factor and nerve growth factor potentiate excitatory synaptic transmission in the rat visual cortex[J]. J Physiol, 1997, 498(1): 153–164. doi: 10.1113/jphysiol.1997.sp021848
    [131]
    Vanevski F, Xu B. Molecular and neural bases underlying roles of BDNF in the control of body weight[J]. Front Neurosci, 2013, 7: 37. doi: 10.3389/fnins.2013.00037
    [132]
    Lemarchand E, Maubert E, Haelewyn B, et al. Stressed neurons protect themselves by a tissue-type plasminogen activator-mediated EGFR-dependent mechanism[J]. Cell Death Differ, 2016, 23(1): 123–131. doi: 10.1038/cdd.2015.76
    [133]
    Zhang W, Shi Y, Peng Y, et al. Neuron activity–induced Wnt signaling up-regulates expression of brain-derived neurotrophic factor in the pain neural circuit[J]. J Biol Chem, 2018, 293(40): 15641–15651. doi: 10.1074/jbc.RA118.002840
    [134]
    von Gall C, Duffield GE, Hastings MH, et al. CREB in the mouse SCN: a molecular interface coding the phase-adjusting stimuli light, glutamate, PACAP, and melatonin for clockwork access[J]. J Neurosci, 1998, 18(24): 10389–10397. doi: 10.1523/JNEUROSCI.18-24-10389.1998
    [135]
    Gau D, Lemberger T, von Gall C, et al. Phosphorylation of CREB Ser142 regulates light-induced phase shifts of the circadian clock[J]. Neuron, 2002, 34(2): 245–253. doi: 10.1016/S0896-6273(02)00656-6
    [136]
    Badura L, Swanson T, Adamowicz W, et al. An inhibitor of casein kinase Iϵ induces phase delays in circadian rhythms under free-running and entrained conditions[J]. J Pharmacol Exp Ther, 2007, 322(2): 730–738. doi: 10.1124/jpet.107.122846
    [137]
    Lee B, Almad A, Butcher GQ, et al. Protein kinase C modulates the phase-delaying effects of light in the mammalian circadian clock[J]. Eur J Neurosci, 2007, 26(2): 451–462. doi: 10.1111/j.1460-9568.2007.05664.x
    [138]
    Bonsall DR, Lall GS. Protein kinase C differentially regulates entrainment of the mammalian circadian clock[J]. Chronobiol Int, 2013, 30(4): 460–469. doi: 10.3109/07420528.2012.741170
    • Related Articles

Catalog

    Figures(3)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (2042) PDF downloads (589) Cited by()
    Related

    ©2023 by the Editorial Department of the Journals of Nanjing Medical University. All rights reserved.   苏ICP备05071376号-5

    Supported by: Beijing Renhe Information Technology Co., Ltd. E-mail: info@rhhz.net  Baidu Analytics

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return