PSD-93 up-regulates the synaptic activity of corticotropin-releasing hormone neurons in the paraventricular nucleus in depression

This study constitutes the first observation of an increased density of PSD-93-CRH co-localized neurons in the hypothalamic paraventricular nucleus (PVN) of patients with major depression. PSD-93 overexpression in CRH neurons in the PVN induced depressi on-like behaviors in mice, accompanied by increased serum corticosterone level. PSD-93 knockdown relieved the depression-like phenotypes in a lipopolysaccharide (LPS)-induced depression model. Electrophysiological data showed that PSD-93 overexpression increased CRH neurons synaptic activity, while PSD-93 knockdown decreased CRH neurons synaptic activity. Furthermore, we found that LPS induced increased the release of glutamate from microglia to CRH neurons resulted in depression-like behaviors using fiber photometry recordings. Together, these results show that PSD-93 is involved in the patho genesis of depression via increasing the synaptic activity of CRH neurons in the PVN, leading to the hyperactivity of the HPA axis that underlies depression-like behaviors.
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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