Studying the Effects of Peripheral Inflammation, Specifically Urinary Tract Infections, on Neuroplasticity

Abstract

Several clinical cases have reported that urinary tract infections (UTI) cause cognitive deficits mainly in elderly patients increasing the chances of developing neuropsychiatric disorders. A study has shown that UTIs reduced neurogenesis, caused inflammation to the urinary tract and induced visceral pain. In this project, adult male Sprague-Dawley rats received transurethral instillation of LPS to their bladders to mimic UTI-associated inflammation. Here, we aim to investigate the effect of peripheral inflammation in the urothelium on adult hippocampal neurogenesis. Control groups were instilled with sterile saline. Bromodeoxyuridine (BrdU) analog (200mg/kg, i.p) was injected 24 hours before the euthnasia in order to assess hippocampal neural stem cells (NSCs) proliferation. Rats were euthanized 3 days following LPS instillation. Behavioral tests including, Y-maze, and Novel Object Recognition, were used to assess reference and recognition memory respectively. Thermal and mechanical sensitivity were assessed following the instillation of LPS. RT-qPCR was done on bladder and hippocampal tissue to measure the mRNA transcription level of cytokines and neurotrophins. Brain sections were stained using fluorescent probes to count the number of BrdU-positive cells. Rats that received LPS were more sensitive to pain in both thermal and mechanical test. In addition, the LPS group had a higher level of IL-1β mRNA in the bladder. However, both groups had similar numbers of BrdU-positive cells in the dentate gyrus of the hippocampus and performed similarly in both the Y-maze and Novel Object Recognition test.