Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Gut microbiota dysfunction (dysbiosis) is implicated in the pathology of AD and is associated with several detrimental consequences, including neurotransmitter depletion, oxidative stress, inflammation, apoptosis, and insulin resistance, which all contribute to the onset of AD. The objective of this study was to assess the effectiveness of Probiotics Fermentation Technology (PFT), a kefir product, in alleviating AD symptoms via regulation of the gut microbiota using a streptozotocin- (STZ-) induced AD mouse model and to compare its activity with simvastatin, which has been proven to effectively treat AD. Mice received one intracerebroventricular injection of STZ (3 mg/kg). PFT (100, 300, 600 mg/kg) and simvastatin (20 mg/kg) were administered orally for 3 weeks. PFT supplementation mitigated STZ-induced neuronal degeneration in the cortex and hippocampus, restored hippocampal acetylcholine levels, and improved cognition in a dose-dependent manner. These effects were accompanied by reductions in oxidative damage, proinflammatory cytokine expression, apoptosis, and tau hyperphosphorylation. Moreover, PFT hindered amyloid plaque accumulation via the enhancement of insulin-degrading enzyme. These beneficial effects were comparable to those produced by simvastatin. The results suggest that PFT can alleviate AD symptoms by regulating the gut microbiota and by inhibiting AD-related pathological events.

Highlights

  • Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder [1]

  • We explore the potential effects of Probiotics Fermentation Technology (PFT) in the treatment of AD, as well as comparing its activity with simvastatin, which has been proven to treat dementia, reduce cognitive decline in AD patients, and diminish the prevalence of AD [21, 22]

  • Animals treated with PFT (100, 300, and 600 mg/kg) displayed a substantial increase in the time spent in the target quadrant in which the platform was previously located (2.9, 3.4, and 4-fold, respectively) as compared with the STZ group (F ð5, 66Þ = 125, p < 0:0001)

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Summary

Introduction

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder [1]. The pathophysiological aspects of AD have not yet been fully investigated; synaptic dysfunction, membrane permeabilization, oxidative stress, inflammation, apoptosis, and a reduction in cerebral glucose utilization have been identified as risk factors of AD progression [4, 5]. It has recently been proposed that gut microbiota dysfunction (dysbiosis) correlates with the onset of AD [6, 7]. This hypothesis is based on many lines of evidence. AD is intricately interrelated with gut microbiota imbalance and may initiate from the gut To this end, the modulation of Oxidative Medicine and Cellular Longevity the gut microbiota has become of increasing interest in the quest for new AD therapeutic agents

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