title: Hippocampal CLOCK protein participates in the persistence of depressive-like behavior induced by chronic unpredictable stress.
abstract: BACKGROUND
  Circadian disturbances are strongly linked with major depression. The circadian proteins CLOCK and BMAL1 are abundantly expressed but function differently in the suprachiasmatic nucleus (SCN) and hippocampus. However, their roles in depressive-like behavior are still poorly understood.
  
  
  OBJECTIVE
  To investigate the alterations of CLOCK and BMAL1 in the SCN and hippocampus in rats subjected to chronic unpredictable stress (CUS) and to explore the relationship of circadian protein and the depressive-like behavior.
  
  
  RESULTS
  Together with depressive-like behavior induced by CUS, CLOCK and BMAL1 in the SC were inhibited during the light period, and the peak expression of CLOCK in the hippocampus was shifted from the dark to light period. BMAL1 expression in the hippocampus was not significantly changed. Two weeks after the termination of CUS, abnormalities of CLOCK in the CA1 and CA3 endured, with unchanged depressive-like behavior, but the expression of CLOCK and BMAL1 in the SCN recovered to control levels. Knockdown of the Clock gene in CA1 induced depressive-like behavior in normal rats. CLOCK in the SCN and hippocampus may participate in the development of depressive-like behavior. However, CLOCK in the hippocampus but not SCN was involved in the long-lasting effects of CUS on depressive-like behavior. BMAL1 in the hippocampus appeared to be unrelated to the effects of CUS on depressive-like behavior.
  
  
  CONCLUSIONS
  CLOCK protein in the hippocampus but not SCN play an important role in the long-lasting depressive-like behavior induced by CUS. These findings suggest a novel therapeutic target in the development of new antidepressants focusing on the regulation of circadian rhythm.
authors.affiliation: National Institute on Drug Dependence, Peking University, 38, Xue Yuan Road, Beijing, 100191, China.
authors.forename: Wen-Gao
authors.initials: WG
authors.lastname: Jiang
authors.forename: Su-Xia
authors.initials: SX
authors.lastname: Li
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Shuang-Jiang
authors.initials: SJ
authors.lastname: Zhou
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D056930:ARNTL Transcription Factors / Q000096:biosynthesis*; D000818:Animals; D056926:CLOCK Proteins / Q000096:biosynthesis*; D002908:Chronic Disease; D003863:Depression / Q000378:metabolism* / Q000523:psychology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*
chemical_list: D056930:ARNTL Transcription Factors; D056926:CLOCK Proteins; C538945:Clock protein, rat