Abstract
The hippocampus, which provides cognitive functions, has been shown to become highly vulnerable during aging. One important modulator of the hippocampal neural network is the medial septum (MS). The present study attempts to determine how age-related mnemonic dysfunction is associated with neurochemical changes in the septohippocampal (SH) system, using behavioral and immunochemical experiments performed on young-adult, middle-aged and aged rats. According to these behavioral results, the aged and around 52.8% of middle-aged rats (within the “middle-aged-impaired” sub-group) showed both impaired spatial reference memory in the Morris water maze and habituation in the open field. Immunohistochemical studies revealed a significant decrease in the number of MS choline acetyltransferase immunoreactive cells in the aged and all middle-aged rats, in comparison to the young; however the number of gamma-aminobutyric acid-ergic (GABAergic) parvalbumin immunoreactive cells was higher in middle-aged-impaired and older rats compared to young and middle-aged-unimpaired rats. Western Blot analysis moreover showed a decrease in the level of expression of cholinergic, GABAergic and glutamatergic receptors in the hippocampus of middle-aged-impaired and aged rats in contrast to middle-aged-unimpaired and young rats. The present results demonstrate for the first time that a decrease in the expression level of hippocampal receptors in naturally aged rats with impaired cognitive abilities occurs in parallel with an increase in the number of GABAergic neurons in the MS, and it highlights the particular importance of inhibitory signaling in the SH network for memory function.
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The design of this study, analysis, interpretation of data and writing the manuscript was supported by the funding from the Shota Rustaveli National Science Foundation of Georgia (SRNSFG): Grant—# FR-18-11783.
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MB and MD contributed to conception and design; MB, MD, VL and RS contributed to analysis and interpretation of data in the manuscript; GB, LK, NC, MC, and LT managed the data collection. Statistical analysis was done by MB, RS and VL. RS and TN revised the manuscript; all authors agreed to be accountable for all aspects of the work. All authors read and approved the final manuscript.
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Burjanadze, M.A., Dashniani, M.G., Solomonia, R.O. et al. Age-related changes in medial septal cholinergic and GABAergic projection neurons and hippocampal neurotransmitter receptors: relationship with memory impairment. Exp Brain Res 240, 1589–1604 (2022). https://doi.org/10.1007/s00221-022-06354-2
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DOI: https://doi.org/10.1007/s00221-022-06354-2