Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice

Area of Science:

• Neuroscience
• Microbiology
• Pharmacology

Background:

• Trimethylamine-N-oxide (TMAO), a gut microbial metabolite, is linked to Alzheimer's disease (AD) progression.
• Probiotics show potential in mitigating AD symptoms by inhibiting TMAO synthesis.

Purpose of the Study:

• To investigate the correlation between TMAO levels and cognitive decline in an AD mouse model.
• To evaluate the therapeutic effects of L. plantarum and memantine on cognitive function and AD pathology.

Main Methods:

• Choline-treated APP/PS1 mice (an AD model) were used to measure plasma TMAO levels.
• Mice received either no treatment, memantine, L. plantarum, or a combination of memantine and L. plantarum for 12 weeks.
• Cognitive function, hippocampal Aβ levels, neuronal integrity, neuroinflammation, and gut microbiota composition were assessed.

Main Results:

• Reduced L. plantarum levels in the gut correlated with cognitive impairment.
• Combined treatment with memantine and L. plantarum ameliorated cognitive deterioration.
• The combined treatment decreased hippocampal Aβ levels, protected neuronal plasticity, and reduced TMAO synthesis and neuroinflammation.

Conclusions:

• L. plantarum enhances the therapeutic efficacy of memantine in an AD mouse model.
• This enhancement is achieved by remodeling the gut microbiota, inhibiting TMAO production, and reducing clusterin levels.
• Targeting the intestinal microbiota presents a potential therapeutic strategy for reducing AD risk.