Nurr1 expression is regulated by voltage-dependent calcium channels and calcineurin in cultured hippocampal neurons

•We investigated the molecular mechanisms for the Nurr1 expression in neurons.•The Nurr1 levels were enhanced by activation of the CNS neurons.•Voltage-dependent calcium channels were responsible for the Nurr1 induction.•We found that calcineurin was critical for the induction of the Nurr1 gene.

Nurr1 is an orphan nuclear transcription factor expressed in the brain. While Nurr1 is assumed to be an immediate early gene, it is not fully understood how Nurr1 expression is regulated in an activity-dependent manner in the central nervous system. Here, we investigated the molecular mechanisms underlying the regulation of Nurr1 expression in cultured hippocampal and cortical neurons. We found that upregulation of neural activity by high KCl and bicuculline enhances Nurr1 levels, while blockade of its activity by tetrodotoxin reduces Nurr1 levels. The induction of Nurr1 expression was mediated by voltage-dependent calcium channels (VDCCs), as shown by cadmium and VDCC-specific inhibitors. Furthermore, calcineurin, but not calcium/calmodulin-dependent protein kinase (CaMK) was critical for the induction. Thus, Nurr1 expression is regulated by VDCC and calcineurin in a cell-autonomous, neural activity-dependent manner.

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