Bone morphogenetic protein-2 promotes survival and differentiation of striatal GABAergic neurons in the absence of glial cell proliferation.
We examined the potential neurotrophic effects of bone morphogenetic protein (BMP)-2 on the survival and differentiation of neurons cultured from the rat developing striatum at embryonic day 16, a period during which the mRNAs for BMP-2 and its receptor subunits (types IA, IB, and II) were detected. BMP-2 exerted potent activity to promote the survival of striatal neurons and increased the number of surviving microtubule-associated protein-2-positive cells by 2.4-fold as compared with the control cultures after 4 days in vitro. Although basic fibroblast growth factor (bFGF) also showed relatively high activity to promote the survival of striatal neurons, transforming growth factor-beta1, -beta2, and -beta3, glial cell line-derived neurotrophic factor, or brain-derived neurotrophic factor promoted their survival weakly. Striatal neurons cultured in the presence of BMP-2 or bFGF possessed extensive neurite outgrowths, the majority of which were GABA-immunoreactive. Inhibition of glial cell proliferation by 5-fluorodeoxyuridine did not affect the capacity of BMP-2 to promote the survival of striatal GABAergic neurons. In contrast, the ability of bFGF to promote the survival of striatal neurons was inhibited significantly by the treatment of cells with 5-fluorodeoxyuridine. All these results suggest that BMP-2 exerts potent neurotrophic effects on the striatal GABAergic neurons in a glial cell-independent manner.
Hattori
A
A
Laboratory of Cell Biology, Gifu Pharmaceutical University, Japan.
Katayama
M
M
Iwasaki
S
S
Ishii
K
K
Tsujimoto
M
M
Kohno
M
M
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D004622:Embryo, Mammalian; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525720:Bmp2 protein, rat; C525811:Bmp4 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D019208:Brain-Derived Neurotrophic Factor; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D016222:Fibroblast Growth Factor 2; D005680:gamma-Aminobutyric Acid