Neuroscience
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/32553
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Browsing Neuroscience by Author "Jones, Kylie"
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Item Changes in Cerebral Mitochondrial Function in Postpartum Dams Exposed to a Low-resource Environment during Weaning(2024-03-21) Jones, Kylie; Smith, Savanna; Smith, Jonna; Castillo, Angie; Powell, Madison; Cunningham, MarkBackground: Postpartum depression is a serious mental-health condition, affecting over 14% of all mothers in the U.S. Poverty, a lack of educational and economic resources, is a major determinant of adult mental health. In the U.S., poverty impacts 11% of adults, with a greater incidence in women of childbearing age (roughly 16%) and postpartum women (roughly 14%). While pregnancy and poverty separately increase risks of developing depression, few studies have combined these conditions to determine their role in the development of depression. Further, no studies have explored mechanisms contributing to depression following pregnancy and poverty. However, cerebral mitochondrial dysfunction (C-mtDys) may be one mechanism. The aim of this study is to examine C-mtDys in postpartum (PP) dams exposed to the limited-bedding-nesting (LBN) model in rats, which reduces their nesting material to simulate a low-resource environment. We hypothesize that PP dams in the LBN model will exhibit C-mtDys and elevated oxidative stress. Methods. Pregnant Sprague-Dawley rats gave birth naturally and were divided randomly into LBN (n =2) or control (n = 2) groups. LBN dams were exposed to the LBN model from PD 2 through PD 9. To validate the success of the LBN model, entropy scores, which are a measure of behavior unpredictability, were recorded for each dam. At 17 weeks PP, equivalent to 8 years PP in humans, brains were collected and used to isolate mitochondria through differential centrifugation. Mitochondrial function was evaluated via respiration (mtRes) using respiratory states. Oxidative stress in the whole brain was examined through H2O2 and total antioxidant capacity biochemical assays. Results. LBN PP dams displayed higher entropy scores (1.10 ± 0.04 v. 0.79 ± 0.04, p < 0.05), as expected based on prior literature, serving as validation of the model. At 17 weeks, PP LBN dams had reduced mtRes in all states, including the basal state (176.09 ± 5.90 v. 360.70 ± 7.73 pmol/s/mg, ns), State 2 (1044.72 ± 14.00 v. 1703.00 ± 18.10 pmol/s/mg, ns), State 3 (3843.27 ± 31.86 v. 6705.72 ± 37.54 pmol/s/mg, ns) and State 4 (776.83 ± 13.65 v. 1533.54 ± 16.46 pmol/s/mg, ns). PP LBN dams exhibited reduced total antioxidant capacity by roughly 20% (54.10 ± 1.24 v. 63.04 ± 0.99 mM Trolox) and elevated H2O2 by roughly 50% (2.12 ± 0.52 v. 1.35 ± 0.28 nM/mg, ns). Summary. In summary, preliminary data shows C-mtDys via reduced mtRes in PP dams exposed to an impoverished environment during weaning. Furthermore, this study suggests that decreased mtRes could contribute to increased oxidative stress in the brain. Elevated oxidative stress may cause damage at the cellular and circuitry levels in the brain that could facilitate the development of depression later in life. Future studies will further examine C-mtDys, oxidative stress, and depressive behaviors in PP dams exposed to LBN. This study is significant because it identifies C-mtDys as a possible mechanism causing depression after exposure to both pregnancy and poverty.Item Early psychosis structural abnormalities in the midbrain correlate with positive and negative symptoms(2024-03-21) Zhou, Zicong; Jones, Kylie; Ivleva, Elena; Colon-Perez, LuisEarly psychosis (EP) is a critical period in developing psychotic disorders. During the EP period, timely intervention strategies can effectively mitigate symptoms of psychotic disorders. A primary target in current therapeutics for psychotic disorders is the dopaminergic system; however, current therapeutics are often inadequate in treating the advanced stages of psychotic disorders. Currently, there are hypotheses that the advent of psychotic disorders are alterations in the brain’s structure and functional connectivity leading to aberrant network organization. Given the prominence of the midbrain in synthesizing dopamine and being a hub in the circuitry of dopaminergic function in this study, we will quantify the structural properties of the midbrain using a publicly available dataset of EP subjects. The Human Connectome Project (HCP) is a global effort to determine human brain connectivity objectively. Specifically, there is a subset where the focus is on subjects within five years of their first psychotic episode, which is the focus of this study. In this project, we employ various computational tools (including FSL, ANTs, packages of Python and RStudio, etc.) to acquire relevant measures of brain structure in EP. Specifically, we performed gross anatomical analysis of brain volumetrics, regional microstructural analysis, and correlation analysis between brain and behavior indices. First, Deformation-based Morphometry (DBM) is a test performed on T1 MRI scans to determine brain volumes. DBM measures shape movements to align individuals with a registration template using the Jacobian determinant (JD), whereas a standard VBM focuses on voxel intensity differences between individuals and the template. In our results, DBM revealed mild changes around the midbrain between EP and healthy controls. Second, we analyzed Diffusion Tensor Imaging (DTI) data by obtaining indices such as Fractional Anisotropy (FA), Axial Diffusivity (AD), and Mean Diffusivity (MD). A midbrain mask was created based on Freesurfer atlas ROI labels, allowing a seed-based analysis centered around the midbrain. Group differences were estimated using the Welch two-group t-tests on ROI means of JD, FA, AD, MD, and midbrain volumes. Interestingly, group differences in JD and midbrain volumes were insignificant, but differences were more pronounced for FA, AD, and MD. Third, we employed Tract-Based Spatial Statistics (TBSS) to determine microstructural changes in white matter tracts. TBSS successfully captured structural variabilities within the midbrain, aligning with our study’s expectations, in addition to moderate changes in other main white matter tracts, such as corticospinal tract and cingulum, suggesting an initiation of altered brain connectivity emanating from alterations in the midbrain or a putative reorganization of dopaminergic circuitry. Fourth, correlations between these quantities in the EP group and behavioral scores (i.e., PANSS and CAINS tests) were explored. It is found that midbrain volume noticeably correlates with the Cognitive score of PANSS and JD, strongly correlates with AD and MD; FA correlates with the Negative score of PANSS, and MD correlates with the Positive score of PANSS. Overall, these findings contribute to understanding midbrain involvement in early psychosis and underscore the interest for further investigation in this research path.