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Glia. 2015 Sep;63(9):1660-70. doi: 10.1002/glia.22837. Epub 2015 Jun 1.

Striatal astrocytes transdifferentiate into functional mature neurons following ischemic brain injury.

Duan CL1,2, Liu CW1,2, Shen SW1,2, Yu Z3, Mo JL1,2,4, Chen XH1,2, Sun FY1,2,4.

Author information

1
Department of Neurobiology, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
2
Research Unit of Brain Injury, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
3
The Electron Microscopy Core Laboratory, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
4
Research Institute of Aging Biology, Research Center on Aging and Medicine and Institutes for Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.

Abstract

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(+)) reactive astrocytes. The results showed that a portion of striatal GFP(+) 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(+)-Tuj-1(+)) and microtubule associated protein-2 (GFP(+)-MAP-2(+)), respectively. GFP(+) neurons further expressed choline acetyltransferase, glutamic acid decarboxylase, dopamine receptor D2-like family proteins, and the N-methyl-D-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(+) 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(+) cells but not in the astrocyte-like GFP(+) cells, demonstrating that new GFP(+) 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.

KEYWORDS:

brain repair; glia; neural network; neurogenesis; stem cell

PMID:
26031629
PMCID:
PMC5033006
DOI:
10.1002/glia.22837
[Indexed for MEDLINE]
Free PMC Article

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