Elucidation of Therapeutic Effects of Probiotics in Mouse Model of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with age-related cognitive decline. It characterized by a host of neurological and psychiatric symptoms particularly learning and memory deficits. Currently, AD has no treatment that halts the progression of the disease. The gut microbiota modulates gut brain axis by facilitating development of hypothalamic-pituitary-adrenal axis and synthesis of neuromodulators such as GABA, SCFAs, serotonin and BDNF. This study investigated the effect of oral consumption of probiotics; Lactobacillus rhamnosus GG (LGG®) and Bifidobacterium BB 12 (BB-12®) (1x109 CFU) on AlCl3 -induced AD mouse models in comparison with Donepezil. Mice were randomly allocated to six different study groups (n=8). Behavioral tests were conducted to assess effect of AlCl3 (300mg/kg) and probiotics treatment on anxiety and memory through Elevated Plus Maze (EPM), Y-maze, Morris Water Maze (MWM) and Novel Object Recognition (NOR) test. The results indicated that probiotic treatment significantly (p<0.0001) reduced anxiety post AlCl3 exposure. The AlCl3 + LGG®& BB-12® treated group showed significantly (p<0.0001) improved spatial memory in comparison to AlCl3-treated group. Also, significant improvement (p<0.0001) was observed in recognition memory in AlCl3 + LGG®& BB-12®-treated group in comparison to AlCl3-treatedgroup, only. The AlCl3 + LGG®& BB-12®-treated group also exhibited significant improvement (p<0.0001) in spatial memory as compared to AlCl3- treatedgroup, only. Histopathological assessment performed through Congo red staining showed remarkable decrease in amyloid plaque burden within the mice hippocampus observed in the group treated with LGG®& BB-12® post AlCl3 exposure. Effects of selected probiotics on the expression of inflammatory cytokines i.e., TNF-α and IL-1β XX was also evaluated through real time PCR. Differential expression of TNF-α and IL-1β was observed in controls and AlCl3-treated group. Whereas the LGG®& BB-12® treatment post AlCl3 exposuresignificantly decreased (p<0.0001) the expression of the inflammatory cytokines as compared to AlCl3-treatedgroup, only. The present findings indicate that probiotics like LGG®& BB-12® have strong potential to be used as combination therapy for AD by modulating the gut microbiota-brain axis