Open AccessEffect of a Novel Prolyl Endopeptidase Inhibitor, JTP-4819, on Thyrotropin-Releasing Hormone-Like Immunoreactivity in the Cerebral Cortex and Hippocampus of Aged Rats
Author(s) -
Masahiko Shinoda,
Kazuhiro Okamiya,
Katsuo Toide
Publication year - 1995
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.69.273
Subject(s) - hippocampus , thyrotropin releasing hormone , endocrinology , medicine , cerebral cortex , cortex (anatomy) , prolyl endopeptidase , chemistry , hormone , psychology , neuroscience , biochemistry , enzyme
We investigated the effects of a novel prolyl endopeptidase inhibitor, JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N- (phenylmethyl)-1-pyrrolidinecarboxamide), on thyrotropin-releasing hormone (TRH)-like immunoreactivity (TRH-LI) in the cerebral cortex and hippocampus of aged rats. The TRH-LI content of both brain regions in aged rats was significantly lower than that in young rats. A single oral dose of JTP-4819 (3 mg/kg) restored the cortical TRH-LI content in aged rats, while doses of 0.3-3 mg/kg restored it in the hippocampus. Repeated oral administration of JTP-4819 at a dose of 1 mg/kg for 21 days produced a significant increase of TRH-LI in the cerebral cortex, while it did so in the hippocampus at doses of 0.3 and 1 mg/kg. Our findings suggest that JTP-4819 may improve the functioning of TRHergic neurons, which deteriorate with senescence.