Ndrg2, a Novel Gene Regulated by Adrenal Steroids and Antidepressants, Is Highly Expressed in Astrocytes

Abstract

Previously, we cloned a gene from rat hippocampus that now shows homology to Ndrg2, a member of the N-myc downregulated gene (NDRG) family with putative roles in neural differentiation, synapse formation, and axon survival. Following adrenalectomy, hippocampal Ndrg2 mRNA increased in response to glucocorticoids. Ndrg2 mRNA was also upregulated by corticosterone in cerebral cortex and heart. Since Ndrg2 mRNA increased in response to glucocorticoid treatment of cultured astrocytes, we examined its cellular localization in adult brain by in situ hybridization. Ndrg2 mRNA is a prevalent message that is widely expressed throughout the brain, but is more abundant in gray matter than in white matter. Predominant mRNA expression was found in neurogenic regions of the adult brain. Furthermore, Ndrg2 mRNA in these regions was localized to GFAP-positive astrocytes or radial glia. In one of these regions, the subgranular zone of the dentate gyrus, Ndrg2 expression was decreased after adrenalectomy, and was restored to sham-operated levels by corticosterone, indicating that it is under positive regulation by glucocorticoids in vivo. Recently, another group reported that Ndr2/Ndrg2 transcripts in rat frontal cortex were decreased by chronic antidepressant treatment. Because antidepressants may alleviate symptoms of depression by reversing the effects of glucocorticoids, these data suggest that further study of Ndrg2 regulation and function in glia could contribute to understanding the pathogenesis and treatment of depression.

The effect of Ndrg2 expression on astroglial activation

“…In the CNS, Ndrg2 has been reported to be predominantly expressed in astrocytes (Nichols, 2003, Okuda et al, 2008, and to a lesser degree in dystrophic neurons in Alzheimer's disease (AD) (Mitchelmore et al, 2004). Ndrg2 was upregulated by adrenal steroid hormones (Boulkroun et al, 2002, Nichols, 2003, while downregulated by antidepressant and electroconvulsive treatment (Takahashi et al, 2005a). These results suggest that Ndrg2 may be involved in the neurodegenerative and neuropsychiatric diseases.…”

“…In these areas, Ndrg2 mRNA was reduced by day 3 after adrenalectomy and was restored to the sham-operated levels by corticosterone replacement (Nichols, 2003), suggesting that Ndrg2 may be involved in the adrenal steroid-mediated regulation of neurogenesis / gliogenesis. Interestingly, our preliminary experiments revealed expression of Ndrg2 in Nestin-positive, GFAP-positive progenitor cells in the striatum (Chen et al, 2004) after MPTP administration.…”

“…It was also reported that Ndrg2 was expressed near the neurogenic regions such as the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricles (Nichols, 2003). In these areas, Ndrg2 mRNA was reduced by day 3 after adrenalectomy and was restored to the sham-operated levels by corticosterone replacement (Nichols, 2003), suggesting that Ndrg2 may be involved in the adrenal steroid-mediated regulation of neurogenesis / gliogenesis.…”

“…It was also reported that Ndrg2 regulated the production of certain secretory proteins in dendritic cells (Choi et al, 2007, Choi et al, 2010. In the CNS, Ndrg2 has been reported to be predominantly expressed in astrocytes (Nichols, 2003, Okuda et al, 2008, and to a lesser degree in dystrophic neurons in Alzheimer's disease (AD) (Mitchelmore et al, 2004). Ndrg2 was upregulated by adrenal steroid hormones (Boulkroun et al, 2002, Nichols, 2003, while downregulated by antidepressant and electroconvulsive treatment (Takahashi et al, 2005a).…”

“…As Ndrg2 was reported to be expressed predominantly in astrocytes in the CNS (Nichols, 2003, Okuda et al, 2008, we first studied its expression in the quiescent astrocytes in both of the striatum (caudate putamen (CPu)) and the substantia nigra (SN). Ndrg2 was expressed in S100-positive astrocytes in both regions ( Fig.1 A, B I).…”