Containment of neuroimmune challenge by diosgenin confers amelioration of neurochemical and neurotrophic dysfunctions in ketamine-induced schizophrenia in mice

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dc.contributor.authorBen-Azu, Benneth
dc.contributor.authorAdebayo, Olusegun G.
dc.contributor.authorFokoua, Aliance R.
dc.contributor.authorOnuelu, Jackson E.
dc.contributor.authorAsiwe, Jerome N.
dc.contributor.authorMoke, Emuesiri G.
dc.contributor.authorOmogbiya, Itivere A.
dc.contributor.authorOkpara, Oghenemarho L.
dc.contributor.authorOkoro, Jennifer E.
dc.contributor.authorOghenevwerutevwe, Omadevuaye M.
dc.contributor.authorUruaka, Christian I.
dc.date.accessioned2024-03-27T17:09:53Z
dc.date.available2024-03-27T17:09:53Z
dc.date.issued2024
dc.descriptionThe Authors are grateful to the technical staff of the Department of Pharmacology, Faculty of Basic Medical Sciences, Delta State University for their technical assistance during the study.
dc.description.abstractInhibition 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.
dc.description.reviewstatusReviewed
dc.description.scholarlevelGraduate
dc.description.sponsorshipThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
dc.identifier.citationBen-Azu, B., Adebayo, O. G., Fokoua, A. R., Onuelu, J. E., Asiwe, J. N., Moke, E. G., ... Uruaka, C. I. (2024). Containment of neuroimmune challenge by diosgenin confers amelioration of neurochemical and neurotrophic dysfunctions in ketamine-induced schizophrenia in mice. Brain Disorders, 13, 100122. https://doi.org/10.1016/j.dscb.2024.100122
dc.identifier.urihttps://doi.org/10.1016/j.dscb.2024.100122
dc.identifier.urihttps://hdl.handle.net/1828/16296
dc.language.isoen
dc.publisherBrain Disorders
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectschizophrenia
dc.subjectneuroinflammation
dc.subjectdopamine
dc.subjectcognitive symptoms
dc.subjectdiosgenin
dc.titleContainment of neuroimmune challenge by diosgenin confers amelioration of neurochemical and neurotrophic dysfunctions in ketamine-induced schizophrenia in mice
dc.typeArticle

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