The M-1-muscarinic acetylcholine receptor subtype may play a role in learning and memory performance in the hippocampus of neonatal monosodium glutamate-obese rats

Author(s)

Silva, Marcelo Florencio Passos ; Rafael, Christian Pereira ; Silva, Jeferson Rubens Mamona ; Souza E Silva, Tiago Guardia de ; Alponti, Rafaela Fadoni ; Alves, Patricia Lucio ; Sandoval, Maria Regina Lopes ; Abdalla, Fernando Mauricio Francis

• Document type: Journal article
• Source: Behavioural Pharmacology; v. 34, n. 5, p. 12-pg., 2023-08-01.

Abstract

Here, we investigate the effects of obesity induced by monosodium glutamate (MSG) on cognitive impairment and whether this model induces any alteration in the affinity, density, and subtypes of muscarinic acetylcholine receptors (mAChRs) in rat hippocampus. Healthy rats were used as controls, and MSG-obese rats were selected via the Lee index > 0.300. The effects of MSG-induced obesity on hippocampal spatial learning and memory processes were evaluated by using the working memory versions of the Morris' water maze task and the evaluation of mAChRs by binding assay and their subtypes by immunoprecipitation assays. [H-3]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium dissociation constant (K-D) did not differ between control and MSG, indicating that affinity is not affected by obesity induced by MSG. The maximum number of binding sites (B-max) obtained in MSG subjects was lower than that obtained from control rats, indicating a decrease in the expression of total mAChRs. Immunoprecipitation assays reveal a decrease in the expression of M-1 subtype of MSG when compared with control rats (M-2 to M-5 subtypes did not differ between control and MSG). We also observed that MSG promotes a disruption of the spatial working memory which was accompanied by a decrease in the M-1 mAChR subtype in rat hippocampus, thus suggesting deleterious long-term effects besides the obesity. In conclusion, these findings provide new insights into how obesity can influence spatial learning and memory that is hippocampal-dependent. The data suggest that the M-1 mAChR subtype protein expression is a potential therapeutic target. (AU)

• FAPESP's process: 16/24258-5 - Effects of diet-induced obesity and its treatment with exenatide on expression of muscarinic acethylcholine receptor subtypes in rat hippocampus
• Grantee: Fernando Maurício Francis Abdalla
• Support Opportunities: Regular Research Grants