Astrocytic JWA Expression is Essential to Dopaminergic Neuron Survival in the Pathogenesis of Parkinson's Disease. (17th March 2014)

• Record Type: Journal Article
• Authors: Miao, Shu‐Han; Sun, Hong‐Bin; Ye, Yang; Yang, Jing‐Jing; Shi, Yao‐Wei; Lu, Ming; Hu, Gang; Zhou, Jian‐Wei
• Is Part Of: CNS neuroscience & therapeutics. Volume 20:Number 8(2014)
• Page Start: 754
• Page End: 762
• Publication Date: 2014-03-17
• Subjects: Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.12249
• Languages: English
• ISSNs: 1755-5930

Abstract

<abstract abstract-type="main" id="cns12249-abs-0001"> <title>Summary</title> <sec id="cns12249-sec-0001" sec-type="section"> <title>Aims</title> <p>To investigate the role of astrocytic JWA expression in dopaminergic (DA) neuron degeneration and in the pathogenesis of Parkinson's disease (PD).</p> </sec> <sec id="cns12249-sec-0002" sec-type="section"> <title>Methods</title> <p>Conditional astrocytic JWA null (JWA<sup>∆2/∆2</sup>/GFAP‐Cre) mice and U251 glioma cells were used to evaluate the effects of JWA gene on DA neuron degeneration. The oxidative stress‐driven molecular events were determined in both <italic>in vivo</italic> and <italic>in vitro</italic> models.</p> </sec> <sec id="cns12249-sec-0003" sec-type="section"> <title>Results</title> <p>Conditional astrocytic JWA knockout resulted in significant activation of astrocytes measured by increase in glial fibrillary acidic protein‐positive cells (1.34 × 10<sup>3</sup> ± 74.5 vs. 8.44 × 10<sup>3</sup> ± 1.35 × 10<sup>3</sup>, <italic>P </italic><<italic> </italic>0.01) in mouse substantia nigra, accompanied by loss of DA neurons (1.03 × 10<sup>4</sup> ± 238 vs. 6.17 × 10<sup>3</sup> ± 392, <italic>P </italic><<italic> </italic>0.001). Deficiency of JWA significantly aggravated reactive oxygen species (ROS) accumulation in substantia nigra compared with the wild‐type mice. Increasing JWA expression in U251 glioma cells inhibited ROS with a concomitant increase in intracellular glutathione. Furthermore, suppression of IKK<italic>β</italic>‐nuclear factor (NF)‐<italic>κ</italic>B signaling pathway was shown to regulate JWA in a PD model.</p> </sec> <sec id="cns12249-sec-0004" sec-type="section"> <title>Conclusions</title> <p>The JWA gene exerts neuroprotective roles against DA neuronal degeneration via modulating intracellular redox status and NF‐<italic>κ</italic>B signaling pathway and is a potential treatment target for PD.</p> </sec> </abstract>