Life Sciences & Biotechnology
Title : | Neurobehavioral and molecular neuroplasticity differences in stress response circuitry for resilience and vulnerability for post-traumatic stress disorder |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Ashok Kumar Datusalia, National Institute Of Pharmaceutical Education And Research (NIPER), Raebareli, Uttar Pradesh |
Timeline Start Year : | 2022 |
Timeline End Year : | 2024 |
Contact info : | ashokdatusalia@gmail.com |
Equipments : | Fear Conditioning Chambers |
Details
Executive Summary : | Stressful life events impact on brain and bodily function and represent a major risk factor for the development of neuropsychiatric disorders such as depression and PSTD. Neuroimaging studies have shown volumetric reduction/remodelling of neuronal architecture in limbic/cortical brain areas of patients and animal models of chronic stress, thus suggesting that stress-induced maladaptive changes have a primary role in the chain of events leading to development of psychopathology. Although genetic vulnerability may represent a moderating factor, it is not clear what mechanisms address the individual responses towards pro-adaptive or maladaptive course. Aim of this project is the identifications of key factors responsible for both functional synaptic changes and architectural changes induced by acute stress in mPFC-BLA-HPC pathways, to understand better the dynamics of the stress response and identify molecular changes that may trigger stress-related psychopathology. This project will investigate short/long-term cellular/molecular changes in the aftermath of acute stress, linked to functional and architectural changes in the brain, to understand better the dynamics of the stress response. This will help to identify epigenetic changes that may trigger stress-related psychopathology. In this proposed work, we first plan to identify key factors responsible for acute footshock-stress induced differential changes in stress response circuit linked with vulnerable and resilient behavior. We will use qPCR assessment of miRNAs and expression of their target genes at short- and long-term after stress in stress response circuits. Finally, rescue experiments in-vivo will be carried out using pharmacological agents (antidepressant ketamine) to validate the neurobehavioral and molecular differences in PTSD resilient and vulnerable rats. This will establish early understanding about individual differences in stress response as vulnerable and resilient. The long term goal of PI revolves around the possibility of conversion from stress vulnerable to stress resilient. |
Total Budget (INR): | 29,94,020 |
Organizations involved