Probiotic treatment improves the impaired spatial cognitive performance and restores synaptic plasticity in an animal model of Alzheimer s disease

Background and Aim : Studies demonstrate that damage to gut microbiota is associated with some brain disorders including neurodegenerative diseases such as Alzheimer s disease (AD). Accordingly, supporting gut microbiota has been considered as a possible strategy for AD treatment. We evaluated behavioral and electrophysiological aspects of the brain function in an animal model of AD made by intracerebroventricular injection of β-amyloid 1-42 (Aβ).Methods : The Con and Con+Pro rats received vehicle and probiotics respectively. Five groups of Alzheimeric animals were treated by either vehicle including (Alz-2weeks) and (Alz-4weeks) groups or received probiotics including (Pro+Alz), (Pro+Alz+Pro) and (Alz+Pro) groups. Alz (2weeks) and Alz (4weeks) groups were tested behaviourally and electrophysiologically two or four weeks after i.c.v injection of Aβ respectively and three groups including Pro+Alz, Pro+Alz+Pro and Alz+Pro received probiotics for eight weeks before injection of Aβ or four weeks before and two weeks after injection of Aβ or for four weeks after injection of Aβ respectively and then were tested behaviouraly and electrophysiologically. Sham group was subjected to injection of saline (i.c.v) and received the vehicle. Spatial learning and memory was assessed in Morris Water Maze. Also, basic synaptic transmission and long-term potentiation (LTP) were assessed by recording field excitatory postsynaptic potentials (fEPSPs) in hippocampus. Change in anti-oxidant/oxidant factors and some metabolic factors was assessed via measuring plasma level of total anti-oxidant capacity (TAC), malondealdehyde (MDA), Triglyceride (TG), total cholesterol and VLDL. Brain staining was done to confirm β-amyloid accumulation. Fecal bacteria quantification was accomplished to find how probiotic supplement affected gut microbiota.Results : Results showed that while the Alz animals displayed a weak spatial performance, probiotic treatment improved the maze navigation in Pro+Alz+Pro and Pro+Alz groups. Whereas basic synaptic transmission remained unchanged in the Alz rats, LTP was suppressed in this group. Probiotic treatment significantly restored LTP in the Pro+Alz and Alz+Pro groups and further enhanced it in the Con+Pro rats. Fecal bacteria quantification in Alz group had no significant difference with Con group but treatment with probiotics significantly increased it until 100 times compare to Alz group. In ALZ group, an increase in MDA, TG, total cholesterol and VLDL was observed which all these factors significantly decreased by probiotics.Conclusion : This study provides the first proof on positive effects of probiotics on synaptic plasticity.

کلیدواژه ها:

Memory ، synaptic plasticity ، Alzheimer disease ، Probiotic