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Activating adiponergic signaling by AdipoRon treatment elicits rapid antidepressant effect independent to changes in hippocampal synaptic plasticity
Author(s)
Date Issued
2022
Conference
Citation
Yau, S. Y., Formolo, D. A., Lee, T. H. (13 Nov 2022). Activating adiponergic signaling by AdipoRon treatment elicits rapid antidepressant effect independent to changes in hippocampal synaptic plasticity. Neuroscience 2022, San Diego, CA, USA.
Type
Conference Paper
Abstract
Depression is a devastating mental illness with a high lifetime prevalence globally. Currently available antidepressants have a delayed therapeutic onset and poor efficacy, while the recently approved rapid-acting antidepressant Esketamine has psychomimetic side effects for chronic treatment. Therefore, there is an urgent need for better rapid antidepressant treatment options. We have previously shown that adiponectin, an adipocyte-secreted hormone mediates the antidepressant effects of physical exercise via enhancing hippocampal cell proliferation, and that activating adiponectin signaling by its receptor agonist AdipoRon mimics the pro-cognitive effects of physical exercise in diabetic animals. Here we investigated the potential antidepressant effects of sub-chronic (7-day) treatment with AdipoRon (20 mg/kg, i.p), and its underlying mechanisms. Depression/anxiety-like behaviors were assessed using behavioral tests including forced swim test, sucrose preference test, open field test, novelty suppressed feeding and light/dark box test. Our results showed that AdipoRon treatment elicits significant antidepressant and anxiolytic effects in concurrent with an increase in hippocampal cell proliferation. Interestingly, sub-chronic treatment decreased immediate neuronal activation in the ventral hippocampus as indicated by decreased in c-fos immunostaining positive cells, and impaired synaptic plasticity as shown by reduced long-term potentiation formation and BDNF protein expression in the hippocampus. Our current data indicated that AdipoRon treatment elicits antidepressant and anxiolytic effects in association with increased hippocampus cell proliferation, but independent to changes in hippocampal synaptic plasticity. The results have suggested that increase in hippocampal cell proliferation could be important for antidepressant action modulated by adiponergic system. Potential involvement of other brain areas that express adiponectin receptors (e.g. mPFC and dorsal raphe nucleus) warrants further investigation.
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