Activation of GABA(A) receptors facilitates astroglial differentiation induced by ciliary neurotrophic factor in neural progenitors isolated from fetal rat brain.
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 GABA(A) receptor (GABA(A)R), GABA(B)R-1 and GABA(C)R, but not GABA(B)R-2, subunits in neocortical cells before commitment. Sustained exposure to the GABA(A)R agonist muscimol at 100 mumol/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 GABA(A)R 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 GABA(A)R 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.
Yoneyama
Masanori
M
Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kanazawa, Ishikawa, Japan.
Fukui
Masaki
M
Nakamichi
Noritaka
N
Kitayama
Tomoya
T
Taniura
Hideo
H
Yoneda
Yukio
Y
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018682:GABA Agents / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects*; D013997:Time Factors
D020934:Ciliary Neurotrophic Factor; D018682:GABA Agents; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D009118:Muscimol; D001640:Bicuculline