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Transient muscarinic and glutamatergic stimulation of neural stem cells triggers acute and persistent changes in differentiation.
- Source :
-
Neurobiology of disease [Neurobiol Dis] 2014 Oct; Vol. 70, pp. 252-61. Date of Electronic Publication: 2014 Jul 06. - Publication Year :
- 2014
-
Abstract
- While aberrant cell proliferation and differentiation may contribute to epileptogenesis, the mechanisms linking an initial epileptic insult to subsequent changes in cell fate remain elusive. Using both mouse and human iPSC-derived neural progenitor/stem cells (NPSCs), we found that a combined transient muscarinic and mGluR1 stimulation inhibited overall neurogenesis but enhanced NPSC differentiation into immature GABAergic cells. If treated NPSCs were further passaged, they retained a nearly identical phenotype upon differentiation. A similar profusion of immature GABAergic cells was seen in rats with pilocarpine-induced chronic epilepsy. Furthermore, live cell imaging revealed abnormal de-synchrony of Ca(++) transients and altered gap junction intercellular communication following combined muscarinic/glutamatergic stimulation, which was associated with either acute site-specific dephosphorylation of connexin 43 or a long-term enhancement of its degradation. Therefore, epileptogenic stimuli can trigger acute and persistent changes in cell fate by altering distinct mechanisms that function to maintain appropriate intercellular communication between coupled NPSCs.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Chronic Disease
Disease Models, Animal
Epilepsy physiopathology
GABAergic Neurons drug effects
GABAergic Neurons physiology
Gap Junctions drug effects
Gap Junctions physiology
Hippocampus drug effects
Hippocampus physiopathology
Humans
Induced Pluripotent Stem Cells drug effects
Induced Pluripotent Stem Cells physiology
Male
Mice
Neural Stem Cells drug effects
Neurogenesis drug effects
Rats
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate metabolism
Receptors, Muscarinic metabolism
Glutamic Acid metabolism
Muscarinic Agonists pharmacology
Neural Stem Cells physiology
Neurogenesis physiology
Pilocarpine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-953X
- Volume :
- 70
- Database :
- MEDLINE
- Journal :
- Neurobiology of disease
- Publication Type :
- Academic Journal
- Accession number :
- 25003306
- Full Text :
- https://doi.org/10.1016/j.nbd.2014.06.020