Exploring the Neurobiological and Genetic Underpinnings of Schizophrenia through Striatal Glutamate Dynamics

Abstract

Schizophrenia is a complex neuropsychiatric disorder characterised by cognitive, emotional, and behavioural abnormalities. This research proposal investigates the interplay between the striatum, glutamate dysregulation, and genetic factors in the pathophysiology of schizophrenia. The striatum, a key region for motivation and reward processing, integrates information crucial for cognitive functions and is profoundly influenced by glutamate and dopamine signalling. Dysregulation of glutamate in the striatum disrupts these functions, contributing to schizophrenia’s core symptoms such as social withdrawal, apathy, and anhedonia. This study aims to analyse the expression of AMPA and kainate receptor subunits in the striatum, which are critical for excitatory synaptic transmission, to understand their role in the disorder. Furthermore, it explores the impact of mitochondrial dysfunction and oxidative stress, with a focus on 4-Hydroxynonenal (HNE) and altered lactate metabolism, on neuronal health and function. By examining how glutamate dysregulation affects dopamine transmission and identifying genetic factors influencing these processes, the research seeks to elucidate the neurobiological foundations of schizophrenia. The ultimate goal is to inform the development of targeted therapeutic strategies to improve clinical outcomes for individuals with schizophrenia.