Life Sciences & Biotechnology
Title : | Evaluating role of SERCA activation in febrile seizure and its relationship with proinflammatory cytokine release |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Awanish Mishra, National Institute Of Pharmaceutical Education And Research (Niper-G), Karnataka |
Timeline Start Year : | 2022 |
Timeline End Year : | 2024 |
Contact info : | awanish1985@gmail.com |
Details
Executive Summary : | Maintenance of intracellular calcium homeostasis is crucial for proper neuronal function and perturbed calcium homeostasis appears as a common pathogenic feature in several neurological disorders. Sarco/endoplasmic reticulum calcium-ATPase (SERCA) pump is one of the important regulators of cytosolic calcium level. Higher expression of SERCA has been observed in the cerebral cortex of young, while reduced expression is recorded with an increase in age. Expression and activity of the SERCA may alter by acclamation of temperature, however, our understanding about febrile seizure-induced changes in brain SERCA expression is still substantial. Therefore, this study is proposed to investigate the effect of heat stress on the expression of calcium release-related proteins, to understand the relationship between febrile seizures, and expression of SERCA in different brain regions (thalamus, cortex, and hippocampus), and the effect of SERCA modulation in febrile seizures. Considering the higher expression level of SERCA in young age (than old age) makes them more prone to undergo cytokine-mediated downregulation of SERCA and develop febrile seizures. However, the link between proinflammatory cytokines and SERCA expression is yet to be established in febrile seizure. Thus, monitoring the SERCA expression in different brain regions particularly, thalamus, cortex, and hippocampus) appears important to understand the initiation of febrile seizures. The evaluate the effect of heat stress on murine microglia cells will be exposed to heat and cell viability, expression of calcium release related proteins and inflammatory mediators will be analyzed in an experimental model of febrile seizure. A further effect of SERCA modulation on the regional expression of inflammatory mediators will be assessed in experimental febrile seizures using C57BL/6J mice. The insights into the underlying mechanism of febrile seizures will be helpful in developing fundamental knowledge about pathology, diagnostic biomarkers and may provide a new lead for developing therapeutic strategies for febrile seizures. The regional expression will also decipher the role of SERCA in febrile seizures, absence seizures, and temporal lobe seizures. The development of the SERCA-based therapeutic approach may also be useful in the development of novel therapeutic approaches in other neurological disorders sharing common pathological changes such as an imbalance in calcium homeostasis, redox milieu, neuroinflammation, and apoptosis. |
Total Budget (INR): | 31,94,640 |
Organizations involved