Impact of interval training with probiotic (L. plantarum / Bifidobacterium bifidum) on passive avoidance test, ChAT and BDNF in the hippocampus of rats with Alzheimer's disease

Abstract

It has been suggested that gut microbiota dysbiosis can lead to Alzheimer's disease (AD), inducing the production of many AD-related pre-inflammatory cytokines. On the other hand, daily probiotic administration and regular exercise training are assumed to improve clinical AD-related symptoms. To take this line of research further, this study was aimed at investigating the impact of moderate-intensity interval training (MIIT) with a combined administration of Lactobacillus plantarum and Bifidobacterium bifidum (probiotic, BROB) on the passive avoidance test (Shuttle Box), choline acetyltransferase (ChAT) and the brain derived neurotrophic factor (BDNF) in the hippocampus of a rat model of AD. Forty male Wistar rats (280 ± 20 g) were divided into five groups (n = 8 in each) of control, amyloid beta peptide (Aβ), Aβ + MIIT (AD rats undergoing MIIT), Aβ + PROB (AD rats fed Lactobacillus plantarum and Bifidobacterium bifidum), and Aβ + MIIT + PROB (AD rats receiving both treatments). AD was induced by the intra-cerebroventricular injection of Aβ1-42 peptide. MIIT was performed on rodent treadmill for 8 weeks (5 days per week). The probiotic was also fed daily to the related groups for 8 weeks. BDNF and ChAT in the hippocampus were measured by real time PCR (RT-PCR) and immunohistochemistry (IHC), respectively. Cresyl violet staining of brain tissue was performed to evaluate the dead cells. Results of tissue staining showed that the induction of the Alzheimer's led to the destruction of hippocampal cells and induced neurodegeneration (p = 0.001). Results of the shuttle box test showed that short-term memory was improved in the Aβ + MIIT + PROB group compared to the Aβ group, while death cells (dark cells) were decreased in all the other three groups (MIIT, BROB, and Aβ + MIIT + PROB). Levels of ChAT as well as the BDNF mRNA in the Aβ + MIIT + PROB group showed a significant increase compared to the Aβ group. In conclusion, it seems that the use of the combined administration of Lactobacillus plantarum and Bifidobacterium bifidum with interval aerobic exercise can have neuroprotective effects on AD.

Keywords: Alzheimer’s disease; BDNF gene; Bifidobacterium bifidum; Lactobacillus plantarum; Moderate-intensity interval training; Probiotics.