Abstract

Brain-derived neurotrophic factor (BDNF), its receptors and epigenetic modulators, are implicated in the pathophysiology of affective disorders, T2DM and the circadian system function. We used diurnal sand rats, which develop type 2 diabetes (T2DM), anxiety and depressive-like behavior under laboratory conditions. The development of these disorders is accelerated when animals are maintained under short photoperiod (5:19L:D, SP) compared to neutral photoperiod (12:12L:D, NP). We compared rhythms in plasma BDNF as well as BDNF and PER2 expression in the frontal cortex and suprachiasmatic nucleus (SCN) of sand rats acclimated to SP and NP. Acclimation to SP resulted in higher insulin levels, significantly higher glucose levels in the glucose tolerance test, and significantly higher anxiety- and depression-like behaviors compared with animals acclimated to NP. NP Animals exhibited a significant daily rhythm in plasma BDNF levels with higher levels during the night, and in BDNF expression levels in the frontal cortex and SCN. No significant BDNF rhythm was found in the plasma, frontal cortex or SCN of SP acclimated animals. We propose that in sand rats, BDNF may, at least in part, mediate the effects of circadian disruption on the development of anxiety and depressive-like behavior and T2DM.

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