Gene expression in the brain across the hibernation cycle

The purpose of this study was to characterize changes in gene expression in the brain of a seasonal hibernator, the golden-mantled ground squirrel, Sp ermophilus lateralis, during the hibernation season. Very little informatio n is available on molecular changes that correlate with hibernation state, and what has been done focused mainly on seasonal changes in peripheral tis sues. We produced over 4000 reverse transcription-PCR products from eutherm ic and hibernating brain and compared them using differential display. Twen ty-nine of the most promising were examined by Northern analysis. Although some small differences were observed across hibernation states, none of the 29 had significant changes. However, a more direct approach, investigating expression of putative hibernation-responsive genes by Northern analysis, revealed an increase in expression of transcription factors c-fos, junB, an d c-Jun, but not junD, commencing during late torpor and peaking during the arousal phase of individual hibernation bouts. In contrast, prostaglandin D2 synthase declined during late torpor and arousal but returned to a high level on return to euthermia. Other genes that have putative roles in mamma lian sleep or specific brain functions, including somatostatin, enkephalin, growth-associated protein 43, glutamate acid decarboxylases 65/67, histidi ne decarboxylase, and a sleep-related transcript SD464 did not change signi ficantly during individual hibernation bouts. We also observed no decline i n total RNA or total mRNA during torpor; such a decline had been previously hypothesized. Therefore, it appears that the dramatic changes in body temp erature and other physiological variables that accompany hibernation involv e only modest reprogramming of gene expression or steady-state mRNA levels.