AIMFor further investigating of heat shock transcription factor 1 (HSF1) action in thermoregulation and its physiological mechanism.

METHODSThe relationship among the expression of HSF1 and interleukin 1beta (IL-1beta) mRNA and tumor necrosis factor alpha (TNF-alpha) mRNA in monocytes was studied during the different fever stages in rabbit fever model induced by LPS. The expressions of IL-1beta and TNF-alpha mRNA were measured by RT-PCR assay; HSF1 expression was measured by Western blot.

RESULTS(1) Intravenous injection of LPS produced a double-peak temperature arisen at 60 min and 180 min. (2) The expression of IL-1beta mRNA in monocytes had a peak at 160 min, while the peak of TNF-alpha mRNA expression occurred at 80 min after intravenous injection of LPS. (3) The content of the HSF1 trimer increased gradually after 160 min intravenous injection of LPS. The results indicated that the content of the HSF1 trimer was negative correlation with the expressions of IL-1beta mRNA and TNF-alpha mRNA, and the change in body temperature was a positive correlation with IL-1beta mRNA.

CONCLUSIONIt is possible that HSF1 limits the rise in body temperature by repressing the gene expressions of the endogenous pyrogen, IL-1beta and TNF-alpha.

Animals ; DNA-Binding Proteins ; metabolism ; Fever ; metabolism ; Heat Shock Transcription Factors ; Interleukin-1beta ; metabolism ; Male ; Monocytes ; metabolism ; RNA, Messenger ; genetics ; Rabbits ; Transcription Factors ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.
Animals ; Mice ; Corticotropin-Releasing Hormone/metabolism* ; Nucleus Accumbens/metabolism* ; Receptors, Corticotropin-Releasing Hormone/metabolism* ; Sleep ; Sleep Wake Disorders ; Stress, Psychological/complications*