Changes in the Glutamate/GABA System in the Hippocampus of Rats with Age and during Alzheimer’s Disease Signs Development

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Alena O. Burnyasheva¹, Natalia A. Stefanova¹, Nataliya G. Kolosova^1,a*, and Darya V. Telegina¹

¹Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

^* To whom correspondence should be addressed.

Received August 30, 2023; Revised October 12, 2023; Accepted October 17, 2023

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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). Normalization of the homeostasis has been discussed as a promising strategy for prevention and/or treatment of AD, however, data on the changes in the GABAergic and glutamatergic systems with age, as well as on the dynamics of AD development, are limited. It is not clear whether imbalance of the excitatory/inhibitory systems is the cause or the consequence of the disease development. Here we analyzed the age-related alterations of the levels of glutamate, GABA, as well as 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 the Wistar rats and of the senescence-accelerated OXYS rats, a model of the most common (> 95%) sporadic AD. Our results suggest that there is a decline in glutamate and GABA signaling with age in 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 the development of neurodegenerative processes that are characteristic of AD.

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KEY WORDS: aging, Alzheimer’s disease, glutamate, GABA, hippocampus, OXYS rats

DOI: 10.1134/S0006297923120027

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