Oral Administration of Lactobacillus gasseri and Lacticaseibacillus rhamnosus Ameliorates Amyloid Beta (Aβ)-Induced Cognitive Impairment by Improving Synaptic Function Through Regulation of TLR4/Akt Pathway

口服加氏乳杆菌和鼠李糖乳杆菌可通过调节 TLR4/Akt 通路改善突触功能,从而减轻淀粉样蛋白β (Aβ) 诱导的认知障碍。

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Abstract

This study investigated the anti-amnesic effects of Lactobacillus gasseri (L. gasseri) MG4247 and Lacticaseibacillus rhamnosus (L. rhamnosus) MG4644 in amyloid beta (Aβ)-induced mice. We confirmed that oral administration of L. gasseri MG4247 and L. rhamnosus MG4644 ameliorated cognitive impairment in Aβ-induced mice using Y-maze, passive avoidance, and Morris water maze tests. Oral administration of L. gasseri MG4247 and L. rhamnosus MG4644 protected the antioxidant system by regulating superoxide dismutase levels, reduced glutathione levels, and reduced malondialdehyde contents. Similarly, they attenuated mitochondrial function by decreasing mitochondrial reactive oxygen species levels and increasing mitochondrial membrane potential and ATP levels. In addition, they regulated neuroinflammation and neurotoxicity by modulating the Toll-like receptor 4 (TLR4)/protein kinase B (Akt) pathway. As a result, they enhanced synaptic function by regulating acetylcholine contents, acetylcholinesterase activity, and the expression of synaptic-function-related proteins such as AChE, ChAT, SYP, PSD-95, and GAP-43. Furthermore, the administration of L. gasseri MG4247 and L. rhamnosus MG4644 improved dysbiosis by promoting the growth of beneficial bacteria while suppressing the growth of harmful bacteria. Therefore, these results suggest that L. gasseri MG4247 and L. rhamnosus MG4644 may be used as probiotics to prevent cognitive impairment.

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