CHRONIC PERIPHERAL INFLAMMATION VIA LIPOPOLYSACCHARIDE INSTILLATIONS IMPAIRS HIPPOCAMPAL NEUROGENESIS AND COGNITIVE FUNCTION IN ADULT MALE RAT

Previous reports showed that many cognitive deficits including neuropsychiatric disorders arise in patients exhibiting symptoms of urinary tract infections (UTI). In our laboratory, we have shown that E-coli induced UTI in adult male rats caused a significant decrease in neurogenesis and impaired cognitive and memory skills. No studies have explored the mechanism of action and the effect of chronic inflammation mimicking UTI-associated inflammatory responses on neurogenesis and brain plasticity. Here, we aim to investigate the effect of chronic peripheral inflammation via lipopolysaccharide (LPS) instillations in the urothelium on cognitive functions, memory, and hippocampal neurogenesis. In this study, adult male Sprague-Dawley rats received four transurethral instillations of LPS over a period of 4 days to resemble chronic UTI-like inflammatory state. Sham groups were instilled with sterile saline. Bromodeoxyuridine (BrdU) analog was injected 24 hours before euthanasia to assess hippocampal neural stem cells (NSCs) proliferation. To assess neurogenesis, BrdU was injected 3 weeks before euthanasia. In addition, a battery of behavioral tests including heat sensitivity, open field, Y-maze, and novel object recognition (NOR) tests were used to assess thermal pain, spontaneous/exploratory motor behavior, cognitive ability, and working memory, respectively. This study demonstrated that chronic inflammation induced by repetitive instillations of LPS in the urinary bladder was associated with decreased hippocampal neurogenesis and impairment of cognitive-like behavior in male rats. Thus, this study will provide experimental evidence supporting the association of UTI-associated inflammation and cognitive disorders observed clinically.