Electroconvulsive seizures modulate levels of thyrotropin releasing hormone and related peptides in rat hypothalamus, cingulate and lateral cerebellum

Abstract

We have studied the neuroanatomic extent of electroconvulsive (ECS)-responsive prepro-TRH and TRH-related gene expression and its possible interaction with forced swimming. Young adult male Wistar rats were treated in a 2×2 Latin square protocol of swimming, no swimming, three daily ECS or sham ECS. Sixteen different brain regions were dissected and immunoreactivity measured for TRH ( pGlu–His–Pro–NH 2); TRH–Gly, a TRH precursor; Ps4, a prepro-TRH-derived TRH-enhancing decapeptide, and EEP ( pGlu–Glu–Pro–NH 2). ECS, in addition to elevating TRH–immunoreactivity (TRH–IR), TRH–Gly–IR, Ps4–IR and EEP–IR levels in the limbic regions, as we have previously reported, also significantly increased Ps4–IR levels in hypothalamus, posterior cingulate and lateral cerebellum, and increased TRH–Gly–IR levels in hypothalamus. Interestingly, the combination of ECS and swimming significantly reduced the levels of TRH–Gly–IR in the anterior cingulate compared to the sham ECS-no swim group. The combined use of high-pressure liquid chromatography and the EEP radioimmunoassay (RIA) revealed that pGlu–Tyr–Pro–NH 2 and/or pGlu–Phe–Pro–NH 2 occur in amygdala, anterior cingulate, frontal cortex, entorhinal cortex, lateral cerebellum and striatum and make a substantial contribution to the EEP–IR and TRH–IR. We conclude that ECS can alter the expression and secretion of TRH-related peptides in the hypothalamus, cingulate and lateral cerebellum. Such effects have not previously been reported in these limbic and extra-limbic regions which are increasingly implicated in the autonomic, behavioral and volitional changes which accompany severe depression and its treatment.