Activation of GABAA receptors facilitates astroglial differentiation induced by ciliary neurotrophic factor in neural progenitors isolated from fetal rat brain

• Published in: Journal of neurochemistry 2007-03, Vol.100 (6), p.1667-1679
• Main Authors: Yoneyama, Masanori, Fukui, Masaki, Nakamichi, Noritaka, Kitayama, Tomoya, Taniura, Hideo, Yoneda, Yukio
• Format: Article
• Language: English
• Subjects: astroglial differentiation; Biochemistry; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; commitment; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fundamental and applied biological sciences. Psychology; GABAA receptors; Gene expression; Medical sciences; Molecular biology; neural progenitor cells; Neurology; Neurons; neurospheres; Rodents; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04322.x

Immunocytochemical analysis confirmed the validity of isolation procedures of neural progenitors capable of self‐replication and differentiation from discrete fetal rat brain structures. A reverse transcription‐polymerase chain reaction analysis revealed the expression of particular GABAA receptor (GABAAR), GABABR‐1 and GABACR, but not GABABR‐2, subunits in neocortical cells before commitment. Sustained exposure to the GABAAR agonist muscimol at 100 μmol/L led to significant increases in the mitochondrial activity and the total areas of neocortical neurospheres formed during the cultivation for 12 days in a manner sensitive to a GABAAR antagonist, with lactate dehydrogenase release being unchanged. Moreover, prior sustained exposure to muscimol significantly facilitated the subsequent expression of an astroglial marker protein in cells differentiated by ciliary neurotrophic factor (CNTF) toward an astroglial lineage, with a concomitant decrease in the neuronal marker protein expression, in an antagonist‐sensitive manner on Western blotting analysis. However, muscimol failed to significantly affect the expression of both marker proteins in cells differentiated in either the presence or absence of all‐trans‐retinoic acid. These results suggest that prior activation of GABAAR may preferentially facilitate the commitment by CNTF of neural progenitor cells toward an astroglial lineage after simulation of the self‐replication activity in the developing rat brain.