Evaluation of cellular function and select biomarkers in an adolescent chronic restraint stress animal model of depression / by Martha Graham.
Depression is a highly prevalent mental illness, characterized by both psychological and physiological symptoms. It generates considerable personal and socioeconomic difficulties, and disproportionately affects women. This project’s aim was to utilize the adolescent chronic restraint (aCRS) animal model of depression to investigate the extracellular signal-regulated kinase (ERK) signaling pathway, and biomarkers of oxidative stress and inflammation, to elucidate potential pathophysiological mechanisms of depression. Reproductively intact female Sprauge-Dawley rats were divided into four groups – not-restrained:saline (NRSAL), not-restrained:desipramine (NRDES), restrained:saline (RSAL), and restrained:desipramine (RDES). All rats were postnatal day (PND) 26 upon arrival. Animals entered the restraint period at PND 34(±1) and began treatment with subcutaneous injections of 0.9% saline or desipramine (5 mg/kg) at PND 55(±1). Following the last day of treatment at PND 69(±1), animals were subjected to locomotor activity and the forced swim test (FST). Sacrificing was via decapitation. The hippocampus (HIP) and frontal cortex (FCX) regions of the brain were harvested for western blot analysis. Trunk blood was also collected for serum separation. Western blot analysis was conducted on HIP, FCX, and serum samples. HIP and FCX samples were probed with ERK, pERK, and superoxide dismutase (SOD) primary antibody. Serum samples were probed with C-reactive protein primary antibody. RSAL animals exhibited significantly more immobility behavior in the FST than the NRSAL group, and aCRS-induced immobility was attenuated by antidepressant treatment with desipramine. Significantly lower levels of ERK1/2 activation and SOD expression were observed in the FCX compared with the HIP, but none between groups. Correlation analyses revealed relationships between some of the western blot and behavioral testing data points (e.g., RDES serum CRP expression is positively correlated to FST swimming), as well as between various western blot analysis data points (e.g., HIP SOD expression is positively correlated to HIP ERK1 expression). The purpose of this study was to broadly investigate cellular dysfunction and potential biomarkers of depression using the aCRS model. The results from this research could serve as starting point for investigators to utilize the aCRS model for more in depth examination of the involvement of signal transduction, oxidative stress, and inflammation with the pathophysiology of depression.