Sleep loss changes neuropeptidase expression and activty in rat brain (876.3)

Abstract

The effect of sleep deprivation on proteolytic activity in the central nervous system has not been frequently addressed in the literature. We have started to study the changes on peptidase activities in animal models of paradoxical sleep deprivation (PSD), mainly focusing on metallopeptidases like thimet oligopeptidase (EP24.15) known to process neuropeptides. In the present study, we demonstrated that PSD in rats induces changes both in the expression and activity of EP24.15 in the male rat hypothalamus and striatum tissue extracts. In the hypothalamus, the significant decrease in activity and mRNA levels, after PSD, was only totally reversed after 96h of sleep recovery. In the striatum, albeit significative, changes in mRNA and activity do not parallel changes on protein content. Neurotensin, GnRH, dynorphins, enkephalins, orphanin/nociceptin are among the many neuropeptides whose balance can be modified by the modifications on EP24.15 activity and can be, at least partially, related with many of the physiological changes observed in PSD and during the sleep recovery periods. Grant Funding Source: Supported by FAPESP, CNPq and AFIP