![]() These findings suggest that ELS results in distinct changes in brain functionality that may predispose patients to a worsened pain phenotype. UCPPS patients exposed to ELS also have altered regional cortical centrality patterns compared to both healthy controls and UCPPS patients without ELS exposure ( 20). Adult UCPPS patients exposed to ELS tend to report more widespread pain, more severe functional symptoms (painful urination), poorer self-perceived well-being, and were less likely to have symptom relief after a year follow up ( 7). Recent studies in patients with Urologic Chronic Pelvic Pain Syndrome (UCPPS), which encompasses interstitial cystitis/painful bladder syndrome (IC/PBS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), have uncovered symptomatic and central functional/connectivity features related to ELS exposure. In rodents, ELS disrupts synaptic potentiation within the CA3 layer of the hippocampus ( 18) and decreases neurogenesis in the dentate gyrus ( 19). High ACE exposure rates are associated with smaller hippocampal volumes in adults ( 15, 16), and the reduction in hippocampal volume appears to mediate the relationship between anxiety and ELS ( 17). ![]() ![]() Clinical studies have correlated ELS with elevated resting and responsive cortisol levels in adulthood ( 11). Considering that the hippocampus is a major negative regulator of the hypothalamic-pituitary-adrenal (HPA) axis, disruption of hippocampal integrity can result in unregulated activation of the stress response ( 13, 14). Excess exposure to glucocorticoids during early development, either through pharmacological or physiological sources, significantly impairs the structure, function, and gene expression of the hippocampus ( 12). Many of the long-term effects of ELS are believed to be mediated via impaired development of the hippocampus. A growing base of research looking into the effects of ELS on pain processing has shown a heightened sensitization to painful stimuli, an increased likelihood of developing chronic pain syndromes, and a decreased likelihood of symptom improvement over time ( 7, 10, 11). Experiencing multiple adverse childhood events (ACEs) can permanently alter higher level affective processing ( 6) and is associated with psychiatric disorders including depression and anxiety ( 9). Exposure to early life stress (ELS) has a significant and long-lasting impact on health outcomes later in life, including chronic pain, mood, and metabolic disorders ( 2) and a higher rate of comorbidity among these outcomes ( 3– 8). Hippocampal changes also appear to be related to whole body metabolic outcomes.Īccording to the National Survey of Children's Health, nearly 40% of children in the United States experienced at least one or more serious psychological traumas in 2018 ( 1). Together, these data suggest that NMS in mice reduces left hippocampal volume and may result in mitochondrial dysfunction and reduced neuronal integrity of the right hippocampus in adulthood. A significant negative correlation was observed between body weight and phosphocreatine levels post-WAS in NMS mice, as well as a positive correlation between body weight and glutamine for NMS mice and a negative correlation for naïve mice. The NMS mice showed a trend toward increased body weight and body fat percentage compared to naïve mice. Phosphoethanolamine (PE) levels were decreased in naïve mice after WAS, but not in NMS mice, and WAS increased ascorbate levels in both groups. MRS was performed only on the right hippocampus and both total choline (tCho) and total N-acetylaspartate (tNAA) levels were significantly decreased due to NMS, particularly after WAS. Volumetric analysis of the whole brain revealed that the left hippocampus of NMS mice was 0.038 mm 3 smaller compared to naïve mice. Here, we are using magnetic resonance imaging and spectroscopy (MRI and MRS) to further investigate both NMS- and acute stress-induced changes in the hippocampus of female mice. We have previously reported that adult mice that underwent neonatal maternal separation (NMS) exhibit urogenital hypersensitivity, altered anxiety- and depression-like behaviors, increased adiposity, and decreased gene expression and neurogenesis in the hippocampus. Structural and functional changes within the hippocampus have been shown to contribute to many early life stress-related outcomes. Early life stress exposure significantly increases the risk of developing chronic pain syndromes and comorbid mood and metabolic disorders later in life.
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