Florey Department of Neuroscience and Mental Health - Research Publications
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ItemShort-Term Environmental Enrichment is a Stronger Modulator of Brain Glial Cells and Cervical Lymph Node T Cell Subtypes than Exercise or Combined Exercise and Enrichment(SPRINGER/PLENUM PUBLISHERS, 2021-04)Physical exercise (PE) and environmental enrichment (EE) can modulate immunity. However, the differential effects of short-term PE, EE, and PE + EE on neuroimmune mechanisms during normal aging has not been elucidated. Hence, a cohort of 3-, 8-, and 13-month-old immunologically unchallenged C57BL/6 wild-type mice were randomly assigned to either Control, PE, EE, or PE + EE groups and provided with either no treatment, a running wheel, a variety of plastic and wooden objects alone or in combination with a running wheel for seven weeks, respectively. Immunohistochemistry and 8-color flow cytometry were used to determine the numbers of dentate gyrus glial cells, and the proportions of CD4+ and CD8+ T cell numbers and their subsets from cervical lymph nodes, respectively. An increase in the number of IBA1+ microglia in the dentate gyrus at 5 and 10 months was observed after EE, while PE and PE + EE increased it only at 10 months. No change in astroglia number in comparison to controls were observed in any of the treatment groups. Also, all treatments induced significant differences in the proportion of specific T cell subsets, i.e., CD4+ and CD8+ T naïve (TN), central memory (TCM), and effector memory (TEM) cells. Our results suggest that in the short-term, EE is a stronger modulator of microglial and peripheral T cell subset numbers than PE and PE + EE, and the combination of short-term PE and EE has no additive effects.
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ItemCognition and Related Neural Findings on Methamphetamine Use Disorder: Insights and Treatment Implications From Schizophrenia Research(FRONTIERS MEDIA SA, 2019-12-17)Despite the prevalence of methamphetamine (meth) use disorder, research on meth is disproportionately scarce compared to research on other illicit drugs. Existing evidence highlights cognitive deficits as an impediment against daily function and treatment of chronic meth use. Similar deficits are also observed in schizophrenia, and this review therefore draws on schizophrenia research by examining similarities and differences between the two disorders on cognition and related neural findings. While meth use disorder and schizophrenia are two distinct disorders, they are highly co-morbid and share impairments in similar cognitive domains and altered brain structure/function. This narrative review specifically identifies overlapping features such as deficits in learning and memory, social cognition, working memory and inhibitory/impulse control. We report that while working memory deficits are a core feature of schizophrenia, such deficits are inconsistently observed following chronic meth use. Similar structural and functional abnormalities are also observed in cortical and limbic regions between the two disorders, except for cingulate activity where differences are observed. There is growing evidence that targeting cognitive symptoms may improve functional outcome in schizophrenia, with evidence of normalized abnormal brain activity in regions associated with cognition. Considering the overlap between meth use disorder and schizophrenia, targeting cognitive symptoms in people with meth use disorder may also improve treatment outcome and daily function.
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ItemDuration of Environmental Enrichment Determines Astrocyte Number and Cervical Lymph Node T Lymphocyte Proportions but Not the Microglial Number in Middle-Aged C57BL/6 Mice(FRONTIERS MEDIA SA, 2020-03-18)Environmental enrichment (EE) has been shown to modulate behavior and immunity. We recently reported that both short and long-term EE enhance baseline locomotion and alleviate depressive-like behavior, but only long-term EE affects locomotion adversely in a threatening environment and enhances anxiety-like behavior in middle-age mice. We have now investigated whether the observed changes in behavior after short- and long-term EE were associated with underlying immune changes. Hence, at the end of behavioral testing, mice were sacrificed, and brains and cervical lymph nodes were collected to investigate the differential effects of the duration of EE (short- and long-term) on the number of immunopositive glial cells in the dentate gyrus, CA1, CA2, and CA3 regions of the hippocampus and proportions of T cell subsets in the cervical lymph nodes using immunohistochemistry and flow cytometry, respectively. EE, regardless of duration, caused an increase in microglia number within the dentate gyrus, CA1 and CA3 hippocampal regions, but only long-term EE increased astrocytes number within the dentate gyrus and CA3 hippocampal regions. A significantly higher proportion of CD8+ naive T cells was observed after long-term EE vs. short-term EE. No significant differences were observed in the proportion of central memory and effector memory T cells or early activated CD25+ cells between any of the test groups. Our results suggest that EE, irrespective of duration, enhances the numbers of microglia, but long-term EE is required to modify astrocyte number and peripheral T cell proportions in middle-aged mice. Our findings provide new insights into the therapeutic effects of EE on various brain disorders, which may be at least partly mediated by glial and neuroimmune modulation.