Behavioral and Neurochemical Assessment of Parathyroid Hormone 2 Receptor agonist Tuberoinfundibular Peptide of 39 in Neurological Disorders

Abstract

The objective of the present study is to elucidate the neuroendocrine role of TIP39 peptide in anxiety, depression and memory model with respect to the behavioural, neurochemical, gene expression and morphological changes in rats. In normal rats, ICV administration of TIP39 did not alter the behaviour, physiology and morphology demonstrating that administration TIP39 peptide did not influence the anxiety, depression and memory markers during the normal state. From the interactive study, PTH2R antagonist was used to study the role of TIP39 in ARS model; TIP39 significantly increased the NA and GABA release and significantly decreased the glutamate and newlineCORT level in brain and plasma of ARS rats. This was reversed after PTH2R antagonist administration, indicating that TIP39 has direct role on noradrenergic, glutaminergic/GABAergic and HPA axis system through PTH2 receptor. CUMS rats exhibited significant reduction in sucrose intake, is a potential predictor of depressive state, led to cause energy deprivation, HPA axis abnormality, oxidative damage and inflammation. In this line, TIP39 both the doses (1 nmol and 10 nmol) effectively reversed the CUMS induced abnormalities. In addition to that, TIP39 effectively increased the GAD enzyme activity and decreased the acetyl cholinesterase activity in CUMS rats. CUMS induced abnormality in mineralocorticoid (MR) and glucocorticoid receptor (GR) gene expressions were significantly reversed after TIP39 administration. Moreover, TIP39 both the doses effectively improved the CUMS induced neurodegeneration in hippocampus and prefrontal cortex region. IMPACT OF THE STUDY: In this study, we found that TIP39 was acting through eurological and endocrinological pathway (bi-directionally) during the stressful condition; which is novel and unique to this study. Because of many existing therapies in the treatment of stress exhibited unidirectional approach which was not satisfactory still, since because stress is generated by both brain and endocrine system.