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Role of Adenosine Receptors in Sleep Deprivation-Induced Depression-Like Behaviors

초록/요약

Role of Adenosine Receptors in Sleep Deprivation-Induced Depression-Like Behaviors Sleep deprivation (SD) disrupts homeostatic regulation and increases vulnerability to stress and mood disorders. This study investigated the duration-dependent effects of SD and elucidated the distinct roles of adenosine A1 receptors (A1R) and A2A receptors (A2AR) in behavioral and molecular alterations induced by 24, 48 and 72 h of SD in mice. SD for 48 h and 72 h, but not 24 h, significantly increased immobility time in the tail suspension test (TST) and forced swim test (FST), accompanied by elevated plasma corticosterone(CORT) levels, indicating a duration-dependent stress response. Hippocampal A1R mRNA expression was significantly reduced, whereas A2AR mRNA expression was markedly increased at 48 h and 72 h of SD. Pharmacological blockade of either A1R (DPCPX) or A2AR (SCH) significantly attenuated SD-induced depression-like behaviors and CORT elevation, whereas activation of A1R with the agonist CPA exacerbated depression-like behavior at 24 h and 48 h of SD. These findings suggest that A2AR upregulation may represent a pathological response to prolonged SD, whereas A1R downregulation may reflect compensatory adaptation to sustained receptor activation. Taken together, our results demonstrate that A1R and A2AR play distinct roles in SD-induced depression-like behaviors. Keywords: Sleep deprivation, Adenosine Receptors, Corticosterone, Depression-like behavior

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목차

Ⅰ. INTRODUCTION 1
A. Sleep deprivation and stress 1
B. Adenosine during sleep deprivation 2
C. Adenosine receptors in stress and depression 2
Ⅱ. MATERIALS AND METHODS 5
A. Reagents 5
B. SD-induced stress model 5
C. Experimental design 6
D. Behavioral tests 6
E. Sample collection 8
F. Enzyme-linked Immunosorbent assay 8
G. Quantitative Real-Time PCR 9
H. Statistical analysis 10
Ⅲ. RESULTS 11
A. SD stress-induced depression-like behavior in mice. 11
B. Plasma CORT levels in sleep-deprived mice. 12
C. Effects of A1R/A2AR antagonist on depression-like behavior in sleep deprived mice. 13
D. Effects of A1R/A2AR antagonist on CORT level in sleep-deprived mice. 16
E. A1R and A2AR mRNA expression in the hippocampus of sleep-deprived mice. 18
F. Effects of A1R agonist on depression-like behavior in sleep-deprived mice. 21
IV. DISCUSSION 22
V. CONCLUSION 28
REFERENCES 29

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