Evaluation of glutamatergic neurotransmission in SH-SY5Y-derived neuron-like cells harboring SOD1 gene mutation

Abstract

The cellular systems responsible for regulating the action of the neurotransmitter glutamate play a crucial role in maintaining balance in the central nervous system. Glutamate acts as an excitatory neurotransmitter, performing important functions in neural development, synaptic plasticity, learning, and memory. Dysregulation in glutamatergic neurotransmission can result in abnormalities in excitatory transmission, leading to glutamate excitotoxicity. At high levels, glutamate has the potential to trigger disorders related to neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis, and Huntington's Disease, among others. Amyotrophic Lateral Sclerosis (ALS) results from the death of motor neurons. Although the vast majority of ALS cases occur sporadically, that is, in individuals without a family history of the disease, approximately 10% of cases are familial ALS (fALS) and have a family history. Moreover, fALS tends to have an average onset about ten years earlier than sporadic cases. The discovery of mutations in some genes of patients with familial ALS has brought new perspectives on the possible underlying mechanisms of the disease's development. Among more than 40 genes associated with ALS, this project will emphasize the mutation in SOD1. Thus, this study seeks to elucidate and characterize the synaptic mechanisms in glutamatergic neurons, especially concerning the relationship between the overexpression and G93A mutation of the SOD1 gene and glutamatergic excitotoxicity. For this purpose, techniques of cell culture, transfection with plasmid expressing wild-type or mutant human SOD1, and analysis of synaptic transmission will be used.