title: Effects of light-dark cycle on hippocampal iNOS expression and CREB activation in rats.
abstract: Nitric oxide (NO) is one of the most important interneural signaling molecules mediating hippocampal functions for learning and memory. The diurnal expression of neuronal NO synthase (nNOS) has been well studied. However, the temporal profile and underlying mechanisms of inducible NOS (iNOS) expression in a normal photoperiod or in altered light-dark cycles remain unclear. We examined the temporal profile of iNOS expression in adult male Sprague-Dawley rats maintained in a 12h-light/ 12h-dark photoperiod (12L/12D), which were pre-synchronized for 7 days before the experiment. The protein and mRNA levels of iNOS in the cortex and hippocampus were measured to examine the photic influences on iNOS expression. The results showed rhythmically changes of the levels of iNOS mRNA and protein in the hippocampus, but not in the cerebral cortex. The iNOS mRNA levels peaked at Zeitgeber time (ZT) 6 and ZT22, and the protein levels peaked at ZT8 and ZT18. Notably, the peaks in iNOS mRNA and protein levels in the 12L/12D group were 10 to 12 h apart, and the rhythmic pattern was absent in the 24-h period of the darkness group. In addition, the level of the phosphorylated cAMP response element binding protein (phospho-CREB) was the highest at ZT18, prior to a peak in iNOS mRNA expression at ZT22. A phospho-CREB-iNOS signaling pathway was further confirmed by the interaction of phospho-CREB and the iNOS DNA in histone complexes isolated by chromatin immunoprecipitation at ZT18. In conclusion, the photoperiod affects the diurnal expression of iNOS and activation of CREB in the hippocampus, which provide clues for the possible impact of circadian changes in hippocampal functions.
authors: Division of Cell Physiology and Neuroscience, Graduate Institute of Medical Sciences Taipei Medical University, Taipei 11031, Taiwan, Republic of China.
authors: Chia-Yu
authors: CY
authors: Hsieh
authors: Department of Pediatrics, Taipei Medical University Wan Fang Hospital, Taipei 11696, Taiwan, Republic of China.
authors: Chia-Hsiu
authors: CH
authors: Hung
authors: Department and Institute of Physiology, National Yang-Ming University, Taipei 11221, Taiwan, Republic of China.
authors: Yi-Hsuan
authors: YH
authors: Lee
authors: Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan, Republic of China.
authors: Shu-Ting
authors: ST
authors: Wu
authors: Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan, Republic of China.
authors: Chaur-Jong
authors: CJ
authors: Hu
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology* / Q000502:physiology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D010766:Phosphorylation; D017440:Photoperiod; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat