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.

PTH levels, sleep quality, and cognitive function in primary hyperparathyroidism

“…( Sperman= -0.42, p < 0.05) This is in general accordance with previous research ndings that imply a relationship between high PTH levels and the central nervous system, especially cognition [19,27,28]. The expression of PTH2 receptor (PTH2R) has been found in the cerebral arteries of the central nervous system [29,30], Studies reported that the interaction of the ligand of the PTH2R named as tuberoinfundibular peptide of 39 residues(TIP39) with PTH2R in the brain have in uenced cognition [31][32][33].…”

3‐O‐Acetyl‐11‐keto‐β‐boswellic acid ameliorates chronic unpredictable mild stress induced HPA axis dysregulation in relation with glutamate/GABA aberration in depressive rats

“…25 The CUMS-induced elevated CORT can alter the metabolism of neuroglial cells that could affect the sequence of glutamate/GABA discharge regulated by glutamic acid decarboxylase enzyme in which converts glutamate to GABA in neuronal and glial cells, however it elevates the brain glutamate and reduces the GABA level in depression. 26 Chronic administration of AKBA improves the altered glutamate/GABA level by increasing GAD enzyme activation in neuronal cells of CUMS rats. Such an adaptogenic response produced by AKBA in stressed rats might be due to suppression of hypothalamic glutaminergic neurons.…”

3-O-Acetyl-11-keto-β-boswellic acid ameliorates acquired, consolidated and recognitive memory deficits through the regulation of hippocampal PPAR γ, MMP9 and MMP2 genes in dementia model

“…Animals routing to hidden platform improves the ability to learn the task which is in direction with the hippocampus CA1, CA3 and DG architect and its neuronal actions [ 24 ]. During the seven days trial, retention time was observed and gradual reduction on day-to-day trial was noted, this shows that continuous exposure of identical activity may reduce the retention time thereby accelerating the learning and memory performance, while augmentation of time spent and platform crossing indicates improvement in reference memory [ 25 ]. Administration of AKBA drastically improved the spatial learning and reference memory performance by reducing retention time, increasing time spent and platform crossing to the target zone.…”