peripheral etanercept administration normalizes behavior, hippocampal neurogenesis, and hippocampal reelin and gabaa receptor expression in a preclinical model of depression

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ID: 156527
2018
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Abstract
Depression is a serious psychiatric disorder frequently comorbid with autoimmune disorders. Previous work in our lab has demonstrated that repeated corticosterone (CORT) injections in rats reliably increase depressive-like behavior, impair hippocampal-dependent memory, reduce the number and complexity of adult-generated neurons in the dentate gyrus, decrease hippocampal reelin expression, and alter markers of GABAergic function. We hypothesized that peripheral injections of the TNF-α inhibitor etanercept could exert antidepressant effects through a restoration of many of these neurobiological changes. To test this hypothesis, we examined the effect of repeated CORT injections and concurrent injections of etanercept on measures of object-location and object-in-place memory, forced-swim test behavior, hippocampal neurogenesis, and reelin and GABA β2/3 immunohistochemistry. CORT increased immobility behavior in the forced swim test and impaired both object-location and object-in-place memory, and these effects were reversed by etanercept. CORT also decreased both the number and complexity of adult-generated neurons, but etanercept restored these measures back to control levels. Finally, CORT decreased the number of reelin and GABA β2/3-ir cells within the subgranular zone of the dentate gyrus, and etanercept restored these to control levels. These novel results demonstrate that peripheral etanercept has antidepressant effects that are accompanied by a restoration of cognitive function, hippocampal neurogenesis, and GABAergic plasticity, and suggest that a normalization of reelin expression in the dentate gyrus could be a key component underlying these novel antidepressant effects.
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brymer2018frontiersperipheral Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Kyle J. Brymer;Erin Y. Fenton;Lisa E. Kalynchuk;Hector J. Caruncho
Journal chemical research in chinese universities
Year 2018
DOI
10.3389/fphar.2018.00121
URL
http://journal.frontiersin.org/article/10.3389/fphar.2018.00121/full
Keywords
depression hippocampus neurogenesis etanercept pharmacology

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