Probiotic effects on cognitive performance, hippocampal oxidative stress, and structural damage induced by icv STZ in Alzheimer-like rat model.

Alzheimer's disease (AD) is a deteriorating neurodegenerative disorder defined by cognitive decline and neuronal damage, with oxidative stress and neuroinflammation as central pathological features. Emerging evidence suggests the gut-brain axis is a key modulator in neurodegeneration, highlighting probiotics' potential in mitigating AD progression. This study investigates the effects of Lactobacillus acidophilus ATCC4356, Lactobacillus reuteri DSM 17938, and their combination on cognitive performance, oxidative stress, and hippocampal structure in a streptozotocin (STZ)-induced AD-like rat model. Thirty-Five male Sprague-Dawley rats were randomly assigned to five groups: Sham, AD-like model (STZ), STZ + Ac, STZ + Re, and STZ + Comb. The AD-like model was induced via intracerebroventricular (icv) injection of STZ. Probiotics were administered by gavage for 35 days. Behavioral assessments, including the open field test and Morris water maze, were conducted to evaluate cognitive and anxiety-like behaviors. Hippocampal oxidative stress markers, including malondialdehyde (MDA), glutathione, superoxide dismutase, and catalase , were analyzed biochemically. Additionally, stereological techniques were used to assess hippocampal volume and cellular densities. Behavioral results demonstrated significant improvement in anxiety-like behavior and spatial memory in probiotic-treated groups compared to the STZ group. Biochemical analysis revealed reduced MDA levels and enhanced antioxidant markers following probiotic intervention. Histological and stereological analyses indicated increased neuronal density and reduced glial cell activation in hippocampal subregions (CA1, CA3, DG), though hippocampal volume loss remained unaltered. These findings underscore the neuroprotective potential of probiotics in alleviating AD-related neurodegeneration, possibly through antioxidative and anti-inflammatory mechanisms. Further pre-clinical studies are warranted to optimize probiotic regimens for AD prevention and treatment.