A high fat, sugar, and salt Western diet induces motor‐muscular and sensory dysfunctions and neurodegeneration in mice during aging: Ameliorative action of metformin. (12th September 2021)

• Record Type: Journal Article
• Authors: Hong, Song; Nagayach, Aarti; Lu, Yan; Peng, Hongying; Duong, Quoc‐Viet A.; Pham, Nicholas B.; Vuong, Christopher A.; Bazan, Nicolas G.
• Is Part Of: CNS neuroscience & therapeutics. Volume 27:Number 12(2021)
• Page Start: 1458
• Page End: 1471
• Publication Date: 2021-09-12
• Subjects: amyloid beta and phosphorylated tau in Alzheimer's disease -- metformin -- microglia in neuroinflammation -- neurodegeneration in motor and sensory cortexes -- Western diet combing high saturated fat, sugar and salt; Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.13726
• Languages: English
• ISSNs: 1755-5930

Abstract

Abstract: Aims: To explore the novel linkage between a Western diet combining high saturated fat, sugar, and salt (HFSS) and neurological dysfunctions during aging as well as Metformin intervention, we assessed cerebral cortex abnormalities associated with sensory and motor dysfunctions and cellular and molecular insights in brains using HFSS‐fed mice during aging. We also explored the effect of Metformin treatment on these mice. Methods: C57BL/6 mice were fed with HFSS and treated with metformin from 20 to 22 months of age, resembling human aging from 56 to 68 years of age (an entry phase of the aged portion of lifespan). Results: The motor and sensory cortexes in mice during aging after HFSS diet showed: (A) decreased motor‐muscular and sensory functions; (B) reduced inflammation‐resolving Arg‐1 + microglia; (C) increased inflammatory iNOs + microglia and TNFα levels; (D) enhanced abundance of amyloid‐β peptide and of phosphorylated Tau. Metformin attenuated these changes. Conclusion: A HFSS‐combined diet caused motor‐muscular and sensory dysfunctions, neuroinflammation, and neurodegeneration, whereas metformin counteracted these effects. Our findings show neuroinflammatory consequences of a HFSS diet in aging. Metformin curbs the HFSS‐related neuroinflammation eliciting neuroprotection. Abstract : This report reveals for the first time that Western diet combining high saturated fat, sugar, and salt (HFSS) reduces the motor‐muscular grip strength and sensory responsibility of mice in aging, which corresponds to increases of neurodegeneration, neuroinflammation (the switch from M2 to M1 phenotype of microglia and increased TNFα levels), pTau burden, and Aβ deposition in motor and sensory cortexes. Metformin counteracts the key portion of HFSS effects. These data address the knowledge gap of neurodegenerative consequence of HFSS diet and involved cellular and molecular insights.