Modulation of Hippocampal TLR4/BDNF Signal Pathway Using Probiotics is a Step Closer Towards Treating Cognitive Impairment in NASH Model

ABSTARCT Background and aim: Disturbance of gut microbiota plays a role in induction and progression of non alcoholic steatohepatitis (NASH) and the associated cognitive dysfunction. We supposed that high fat diet (HFD)-induced dysbiosis may lead to NASH/cognitive impairment co-morbidities through hippocampal TLR4/BDNF signaling pathway and the regaining of microbiota balance through probiotics could provide a therapeutic option. Methodology: Four groups of male Wister rats were used; Naive, Lactobacillus Plantarum EMCC-1039 (LP EMCC-1039), NASH and NASH+ LP EMCC-1039 groups. After induction of NASH with high fat diet (HFD), LP EMCC-1039 was given daily by oral gavage in the last two weeks of experiment to the treated group. Body weight percentage (BW%) changes, Lee index (LI), liver function tests, expression of BDNF, TLR4 with RT-PCR and quantification of BDNF, TLR4 by ELISA were measured . Histological studies and assessment of cognitive function were also performed. Results: NASH group showed an increase in BW% and LI . It was associated with cognitive deficits, an increase in hepatic, hippocampal TLR4 expression and decline in BDNF expression and protein, all p values were Conclusions: Dysbiosis-induced NASH was associated with cognitive impairment and a probiotic (LP EMCC-1039) supplementation has beneficial effect through modulation of TLR4/BDNF signaling pathway.