Striatal astrocytes transdifferentiate into functional mature neurons following ischemic brain injury. Issue 9 (1st June 2015)

• Record Type: Journal Article
• Authors: Duan, Chun‐Ling; Liu, Chong‐Wei; Shen, Shu‐Wen; Yu, Zhang; Mo, Jia‐Lin; Chen, Xian‐Hua; Sun, Feng‐Yan
• Is Part Of: Glia. Volume 63:Issue 9(2015:Sep.)
• Page Start: 1660
• Page End: 1670
• Publication Date: 2015-06-01
• Subjects: Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.22837
• Languages: English
• ISSNs: 0894-1491

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>To determine whether reactive astrocytes stimulated by brain injury can transdifferentiate into functional new neurons, we labeled these cells by injecting a glial fibrillary acidic protein (GFAP) targeted enhanced green fluorescence protein plasmid (pGfa2‐eGFP plasmid) into the striatum of adult rats immediately following a transient middle cerebral artery occlusion (MCAO) and performed immunolabeling with specific neuronal markers to trace the neural fates of eGFP‐expressing (GFP<sup>+</sup>) reactive astrocytes. The results showed that a portion of striatal GFP<sup>+</sup> astrocytes could transdifferentiate into immature neurons at 1 week after MCAO and mature neurons at 2 weeks as determined by double staining GFP‐expressing cells with βIII‐tubulin (GFP<sup>+</sup>‐Tuj‐1<sup>+</sup>) and microtubule associated protein‐2 (GFP<sup>+</sup>‐MAP‐2<sup>+</sup>), respectively. GFP<sup>+</sup> neurons further expressed choline acetyltransferase, glutamic acid decarboxylase, dopamine receptor D2‐like family proteins, and the <italic>N</italic>‐methyl‐<sc>d</sc>‐aspartate receptor subunit R2, indicating that astrocyte‐derived neurons could develop into cholinergic or GABAergic neurons and express dopamine and glutamate receptors on their membranes. Electron microscopy analysis indicated that GFP<sup>+</sup> neurons could form synapses with other neurons at 13 weeks after MCAO. Electrophysiological recordings revealed that action potentials and active postsynaptic currents could be recorded in the neuron‐like GFP<sup>+</sup> cells but not in the astrocyte‐like GFP<sup>+</sup> cells, demonstrating that new GFP<sup>+</sup> neurons possessed the capacity to fire action potentials and receive synaptic inputs. These results demonstrated that striatal astrocyte‐derived new neurons participate in the rebuilding of functional neural networks, a fundamental basis for brain repair after injury. These results may lead to new therapeutic strategies for enhancing brain repair after ischemic stroke. GLIA 2015;63:1660–1670</p> </abstract>