Changes in the glutamate/gaba system in the hippocampus of rats with age and during the Alzheimer’s disease signs development

Abstract

GABA and glutamate are the most abundant neurotransmitters in the CNS and play a pivotal part in synaptic stability/plasticity. Glutamate and GABA homeostasis is important for healthy aging and reducing the risk of various neurological diseases, while long-term imbalance can contribute to the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Its normalization discussed as a promising strategy for the prevention and/or treatment of AD, however, data on changes in the GABAergic and glutamatergic systems in with age, as well as in the dynamics of AD development, are limited. It is not clear whether the imbalance of the excitatory/inhibitory systems is a cause or a consequence of the development of the disease. Here we analyzed age-related alterations of the expression of glutamate, GABA, and enzymes that synthesize them (glutaminase, glutamine synthetase, GABA-T, and GAD67), transporters (GLAST, GLT-1, and GAT1), and relevant receptors (GluA1, NMDAR1, NMDA2B, and GABAAr1) in the whole hippocampus of Wistar rats and of senescence-accelerated OXYS rats, a model of the most common (> 95%) sporadic AD. Our results suggest that there is a decline of glutamate and GABA signaling with aging in the hippocampus of the both rat strains. However, we have not identified significant changes or compensatory enhancements in this system in the hippocampus of OXYS rats during development of neurodegenerative processes that are characteristic of AD.