ANALYSIS OF THE EXPRESSION OF ASTROCYTIC GLUTAMATERGIC TRANSPORTERS EAAT1 AND EAAT2 IN THE HIPPOCAMPUS OF PATIENTS WITH TEMPORAL LOBE EPILEPSY AFFECTED OR NOT BY DEPRESSION

• Grant number: 23/13600-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2023
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: José Eduardo Peixoto Santos
• Grantee: Lucas Gabriel Souza Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Epilepsy is a neurological disorder characterized by convulsive episodes marked by involuntary muscle contractions, abnormal visual or auditory perceptions, transient memory alterations, among others. This affliction exhibits significant prevalence not only in Brazil but also globally, particularly in developing countries, leading to diminished quality of life for those affected and generating healthcare costs. In addition to the adverse impact epilepsy imposes on the lives of sufferers, it frequently co-occurs with other psychiatric comorbidities such as psychosis, anxiety, and notably, depression. Multiple studies suggest that depression and temporal lobe epilepsy share similar pathophysiology, with a common involvement of hippocampal and amygdalar projections, as well as long-range frontal lobe projections. Depressive disorders, akin to epilepsy, hold substantial prevalence and exert profound repercussions on an individual's overall health. This ailment is characterized by a prevailing state of depression, feelings of guilt and worthlessness, diminished or absent pleasure in once-enjoyed activities, and even suicidal ideation. Studies indicate an approximate incidence of 5.8% among the Brazilian population, with a higher prevalence among women. Physiologically, astrocytes, glial cells enveloping neuronal synapses, play a pivotal role in regulating glutamate, the principal excitatory neurotransmitter of the central nervous system (CNS). This regulation is achieved through astrocytic clearance of glutamate via transporters that remove it from the extracellular space, facilitating its conversion into glutamine through the enzyme glutamine synthetase (GS). Research demonstrates that failures in this mechanism can foster a hyperexcitability environment in the synaptic cleft, which correlates with the onset of convulsive seizures and depressive symptoms.