Life Sciences & Biotechnology
Title : | The neuroprotective effect of Vitamin D3 involves a phosphatidyl-inositol-3 kinase pathway activation to enhance alpha7 nicotinic acetylcholine receptor function in Schizophrenia |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Neuroscience, Molecular Biology |
Principal Investigator : | Dr. Pragya Komal, Birla Institute Of Technology & Science Pilani (BITS), Hyderabad Campus, Telangana |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | pragya@hyderabad.bits-pilani.ac.in |
Details
Executive Summary : | A new concept of truncated immune receptor protein, T-cell receptor beta subunit (TCR-β) function in the central nervous system is proposed in the present work. Under neuropathological conditions like those observed in Huntington’s disease, we have recently demonstrated that the gene expression of the TCR-β subunit receptor gets robustly elevated in the striatum and the cortex in Huntington’s disease (Komal et al; 2022, IBRO-Neuroscience Reports). In this regard, the contribution of cholinergic signaling is being postulated to play a protective effect across a range of neurocognitive disorders like Schizophrenia, dementia, depression, Alzheimer’s (AD), and Parkinson’s disease (PD). A loss of α7 cholinergic receptors with a subsequent decreased cholinergic function is commonly associated with the cognitive deficit as observed in schizophrenia (SCZ). In spite of the wealth of knowledge that exists regarding SCZ, only a handful of options are available currently for its management. In this context, neurocognitive benefits of nutritional supplementation like Vitamin D3 (Cholecalciferol; VD), come from a wide range of studies conducted on animal models as well as on patients with neuropsychiatric disorders like dementia. Limited information however exists on how VD induction in neurological conditions like SCZ affects immune receptor expression like T-cell receptors (TCR-β) in the brain. Evidence suggests that the TCR receptor beta subunit, a well-characterized immune protein significantly implicated in the cholinergic receptor function regulation in the central nervous system (Komal et al, 2014 and 2022). The study reflected a functional interaction between T-cell receptors (TCR) in modulating α7 receptor cholinergic signaling in a murine model. However, the mechanism of neuroprotection shown by Vitamin D3 and its downstream mechanism of action in neuropathological conditions like those observed in SCZ remains unexplored. Hence, this study will explore whether Vitamin D3 (VD) mediated increase in phosphatidylinositol kinase pathway enhances α7 nAChRs expression and subsequently causes a downregulation in the expression of the immune native protein, TCR-beta subunit (TCR-β) in the schizophrenic brain. Hypothesis Vitamin D3 (VD) mediated increase in Vitamin D receptor (VDR) enhances the surface expression of α7 nAChRs which in turn combats TCR-beta subunit expression in neurons through the phosphatidylinositol kinase (PI-3K) pathway in the prefrontal cortex. |
Total Budget (INR): | 23,98,000 |
Organizations involved