Research Projects

Extracellular vesicles (EVs) are key mediators of intercellular communications, physiological process and aids in maintaining neuronal integrity. In pathogenic conditions, these EVs carry different broad of molecular determinants and misfolded proteins associated with various neurodegenerative and neuropsychiatric disorders. The aggregates of these misfolded proteins are highly resistant to degradative pathway and known to escape clearance due to functional defects in proteolytic system. Hippocampus of the brain is the primary region of neurogenesis within the adult mammalian brain. These adults born neurons aids in the neural circuitry and contribute to cognition throughout life. Consequently, impaired neurogenesis is principally prompted by anomalous neurotransmitter release, imbalanced neurotrophic factors and circulating pathogenic EVs. Furthermore, disruption in neurogenesis has been hypothesized to countersign various neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Multiple Sclerosis. Among various pathogenic determinant, abnormal circulation of EVs appears to be a prominent therapeutic target in the management of neurocognitive impairments. Therapeutic Tetanus toxoid (TT) is a Food and Drug Administration (FDA)-approved vaccine in which the tetanus neurotoxin (TeNT) is rehabilitated by treatment with formaldehyde and lysine into the non-toxic form. The vaccine diffuses and enters the lymphatic system and blood circulations. By retroaxonal transport, TT enter the nerve terminal and prime the blockade of neurotransmitter release from inhibitory interneurons (GABA and glycine). In addition, TT possess the potential role in regulation of inflammatory cytokines, which could be the finest key to offset with major of the inflammatory related disorders mainly like Multiple Sclerosis. However, the role of TT on the regulation of neural stem cells, pathogenic extracellular vesicles and aberrant neurotransmission is yet to be investigated. The proposed study has been designed to assess the effect of TT in the regulation of pathogenicity and hippocampal plasticity in both in vivo and in vitro condition in control and disease conditions like Multiple sclerosis. In the first phase, the effect of therapeutic tetanus toxoid on the modulation of cognitive, depression, anxiety related behaviors would be examined in experimental animals using Morris water maze, elevated plus maze and light dark box. In the second phase, the effect of therapeutic tetanus toxoid on the regulation of hippocampal neuroregenerative plasticity in association with change in key neurotransmitters, extracellular vesicles and miRNAs will be assessed using confocal microscope and FACS. At the end, the effect of therapeutic tetanus toxoid on the fate determination of neural stem cells will be investigated in vitro using live cell imaging and co immunofluorescence techniques.