Molecular mechanism of tuberoinfundibular peptide of 39 on glucocorticoid receptor mediated glutamate/GABA imbalance and cerebral abnormalities against cognitive deficit model

Abstract

Objectives: This study is designed to evaluate the role of tuberoinfundibular peptide of 39 (TIP39) in connection with glucocorticoid receptor-mediated glutamate/GABA abnormalities in chronic unpredictable mild stress (CUMS) model. Methods: Male Sprague–Dawley rats were treated with TIP39 (1 and 10 nmol, i.c.v) and diazepam 2 mg/kg throughout the stress period (28 days) in alternate days. Then, rats were subjected for different behavioural activity followed by biochemical, gene expression and histological examinations. Key findings: Chronic unpredictable mild stress rats showed significant cognitive impairment in Morris water maze, Novel object recognition and Y maze test. This was reversed after TIP39 administration. Moreover, TIP39 significantly decreased the brain glutamate and acetyl cholinesterase levels in CUMS rats, whereas it increases the level of GABA after TIP39 treatment. These changes were evident with increased glutamic acid decarboxylase enzyme activity by TIP39. TIP39 significantly decreased the brain glucocorticoid and mineralocorticoid receptor expression ratio in comparison with CUMS rats. Moreover, histological abnormalities in prefrontal cortex and hippocampus were markedly improved after TIP39 administration in CUMS rats. Conclusions: Tuberoinfundibular peptide of 39 can be a potent neuroendocrine modulator in treating cognitive impairment induced by CUMS rats by controlling glucocorticoid receptor-mediated glutamate/GABA abnormalities in brain.