当前位置： SCI文献检索 > PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY期刊下所有文献 > Carbamoylated erythropoietin induces a neurotrophic gene profile in neuronal cells.

Carbamoylated erythropoietin induces a neurotrophic gene profile in neuronal cells.

Abstract：

:Erythropoietin (EPO), a cytokine molecule, is best-known for its role in erythropoiesis. Preclinical studies have demonstrated that EPO has robust neuroprotective effects that appear to be independent of erythropoiesis. It is also being clinically tested for the treatment of neuropsychiatric illnesses due to its behavioral actions. A major limitation of EPO is that long-term administration results in excessive red blood cell production and increased blood viscosity. A chemical modification of EPO, carbamoylated erythropoietin (CEPO), reproduces the behavioral response of EPO in animal models but does not stimulate erythropoiesis. The molecular mechanisms involved in the behavioral effects of CEPO are not known. To obtain molecular insight we examined CEPO induced gene expression in neuronal cells. PC-12 cells were treated with CEPO followed by genome-wide microarray analysis. We investigated the functional significance of the gene profile by unbiased bioinformatics analysis. The Ingenuity pathway analysis (IPA) software was employed. The results revealed activation of functions such as neuronal number and long-term potentiation. Regulated signaling cascades included categories such as neurotrophin, CREB, NGF and synaptic long-term potentiation signaling. Some of the regulated genes from these pathways are CAMKII, EGR1, FOS, GRIN1, KIF1B, NOTCH1. We also comparatively examined EPO and CEPO-induced gene expression for a subset of genes in the rat dentate gyrus. The CEPO gene profile shows the induction of genes and signaling cascades that have roles in neurogenesis and memory formation, mechanisms that can produce antidepressant and cognitive function enhancing activity.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Tiwari NK,Sathyanesan M,Schweinle W,Newton SS

doi

10.1016/j.pnpbp.2018.07.011

subject

Has Abstract

pub_date

2019-01-10 00:00:00

pages

132-141

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(18)30122-2

journal_volume

88

pub_type

杂志文章

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