Voluntary Wheel Running Improves Hippocampal Integrity, Cognitive Performance, And Urogenital Hypersensitivity In Adult Mice Exposed To Neonatal Maternal Separation

Early life stress (ELS) has been correlated with pain severity and neuroimaging abnormalities in patients with urologic chronic pelvic pain syndrome (UCPPS). Our lab has established an ELS mouse model using neonatal maternal separation (NMS) that recapitulates many clinical features of UCPPS. This study aimed to determine whether exercise could attenuate acute water avoidance stress (WAS)-induced exacerbation of urogenital hypersensitivity and altered hippocampal neurochemical levels in NMS mice. NMS was performed on postnatal days 1-21 and exercise (Ex), in the form of voluntary wheel running, began at 28 days of age. Visceromotor response to urinary bladder distention was attenuated by exercise in NMS-females, suggesting an attenuation of bladder hypersensitivity even post-WAS. Exercise increased baseline prostate mechanical withdrawal threshold in NMS-males but did not prevent WAS-induced sensitivity. H-1Magnetic Resonance Spectroscopy revealed sex and hemisphere-dependent differences in hippocampal neurochemical concentrations post-WAS. In the left-female hippocampus, a WAS effect was observed on total creatine (tCr) and phosphocholine. An interaction of WAS-NMS-Ex was observed on glutamate and phosphocholine. In the right-female hippocampus, we observed a WAS effect on lactate and a WAS-NMS interaction on glutathione and aspartate. In the left-male hippocampus, a WAS effect was observed on lactate, n-acetylaspartate, glutamate, tCr, total choline (tCho), and taurine, as well as a WAS-NMS-Ex interaction on n-acetylaspartate. In the right-male hippocampus, a main effect of WAS and a WAS-NMS interaction was observed for GABA, n-acetylaspartate, tCho, and glutamate. These results suggest complex contributions of NMS, exercise, and stress to perceptions of pain and hippocampal integrity. R01 DK099611.