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Item Containment of neuroimmune challenge by diosgenin confers amelioration of neurochemical and neurotrophic dysfunctions in ketamine-induced schizophrenia in mice(Brain Disorders, 2024) Ben-Azu, Benneth; Adebayo, Olusegun G.; Fokoua, Aliance R.; Onuelu, Jackson E.; Asiwe, Jerome N.; Moke, Emuesiri G.; Omogbiya, Itivere A.; Okpara, Oghenemarho L.; Okoro, Jennifer E.; Oghenevwerutevwe, Omadevuaye M.; Uruaka, Christian I.Inhibition of neuroinflammation through N-methyl-D-aspartate receptor (NMDAR) regulation can provide normalization of neurochemical homeostasis and neurotrophic support in the pathogenesis of psychiatric disorders with complex symptoms such as schizophrenia. Accordingly, the preventive and reversal effects, and potential mechanisms of diosgenin, a phyto-steroidal sapogenin with anti-inflammatory functions, was evaluated in ketamine (an NMDAR antagonist) model of schizophrenia in mice. Adult male mice were allotted into 5 groups. In the preventive protocol, mice received saline (10 mL/kg), diosgenin (25 and 50 mg/kg) and risperidone (0.5 mg/kg) orally for 14 days, with additional injection of ketamine (20 mg/kg/day/i.p.) from days 8–14. In the reversal protocol, mice took ketamine injection consecutively for 14 days prior to diosgenin and risperidone treatments from days 8–14. Thereafter, schizophrenia-like behavior, therapeutic extrapyramidal adverse effect, neuroimmune, neurochemical and neurotrophic consequences in important brain areas affected in the disorder were assayed. Diosgenin prevented and reversed stereotypy behavior, cognitive impairment, and psychotic-depression relative to ketamine groups. Complementarily, diosgenin prevents and reverses ketamine-induced dopamine and serotonin alterations in the striatum, prefrontal-cortex, and hippocampus relative to ketamine groups. Except for the cortical regions, diosgenin prevented and reversed glutamic acid decarboxylase depletion in these brain regions by ketamine, suggesting improved GABAergic system. Additionally, ketamine-induced elevation of neuroinflammatory markers: myeloperoxidase, tumor necrosis factor-alpha and interleukin-6, were inhibited in the striatum, prefrontal-cortex, and hippocampus. Also, diosgenin improved the levels of neurotrophic factor in the three brain regions in both protocols respectively. Among other mechanisms, the antipsychotic effect of diosgenin might be associated with attenuation of neurochemical and neuroimmune alterations.Item Microglial implications in SARS-CoV-2 Infection and COVID-19: Lessons from viral RNA neurotropism and possible relevance to Parkinson's disease(Frontiers in Cellular Neuroscience, 2021) Awogbindin, Ifeoluwa O.; Ben-Azu, Benneth; Olusola, Babatunde A.; Akinluyi, Elizabeth T.; Adeniyi, Philip A.; Di Paolo, Therese; Tremblay, Marie-ÈveSince December 2019, humankind has been experiencing a ravaging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, the second coronavirus pandemic in a decade after the Middle East respiratory syndrome coronavirus (MERS-CoV) disease in 2012. Infection with SARS-CoV-2 results in Coronavirus disease 2019 (COVID-19), which is responsible for over 3.1 million deaths worldwide. With the emergence of a second and a third wave of infection across the globe, and the rising record of multiple reinfections and relapses, SARS-CoV-2 infection shows no sign of abating. In addition, it is now evident that SARS-CoV-2 infection presents with neurological symptoms that include early hyposmia, ischemic stroke, meningitis, delirium and falls, even after viral clearance. This may suggest chronic or permanent changes to the neurons, glial cells, and/or brain vasculature in response to SARS-CoV-2 infection or COVID-19. Within the central nervous system (CNS), microglia act as the central housekeepers against altered homeostatic states, including during viral neurotropic infections. In this review, we highlight microglial responses to viral neuroinfections, especially those with a similar genetic composition and route of entry as SARS-CoV-2. As the primary sensor of viral infection in the CNS, we describe the pathogenic and neuroinvasive mechanisms of RNA viruses and SARS-CoV-2 vis-à-vis the microglial means of viral recognition. Responses of microglia which may culminate in viral clearance or immunopathology are also covered. Lastly, we further discuss the implication of SARS-CoV-2 CNS invasion on microglial plasticity and associated long-term neurodegeneration. As such, this review provides insight into some of the mechanisms by which microglia could contribute to the pathophysiology of post-COVID-19 neurological sequelae and disorders, including Parkinson's disease, which could be pervasive in the coming years given the growing numbers of infected and re-infected individuals globally.Item The Effects of Self-Relevance on Neural Learning Signals Indexing Attention, Perception, and Learning(2022-09-28) Rocha Hammerstrom, Mathew; Krigolson, OlavHumans tend to preferentially process information relevant to themselves. For instance, in experiments where participants learn to manipulate stimuli referenced to themselves or someone else, participants exhibit larger reward processing signals for themselves. Additionally, attention and perception are biased not only towards one’s self but those related to them. However, the aspect of processing information related to known-others has not been addressed in reward learning. Here, I sought to address this issue. Specifically, I recorded electroencephalographic (EEG) data from 15 undergraduate student participants who played a simple two-choice “bandit” gambling game where a photo presented before each gamble indicated whether it benefited either the participant, an individual they knew, or a stranger. EEG data from 64 electrodes on a standard 10-20 layout were analyzed for event-related potentials (ERPs) elicited by target photos and gambling outcomes. Post experiment, I examined the relationship between relatedness and the amplitude reward learning ERPs, namely the reward positivity and the P300, with one-way repeated measures analyses of variance. My results demonstrate that the amplitudes of reward learning ERPs are sensitive to the target of a gamble. A secondary goal of this research was to determine if these differences could be explained by attentional and perceptual responses to cues of who a given gamble was for. Indeed, stepwise linear regression analyses identified the P2, N2, and P3 indexed relevance to self as predictors of resultant reward signals. My findings provide further evidence that a reward learning system within the medial-frontal cortex is sensitive to others with varying self-relevance, which may be a function of biases in attention and perception.