Self-secretion of fibroblast growth factor-9 supports basal forebrain cholinergic neurons in an autocrine/paracrine manner.
We examined the effect of fibroblast growth factor (FGF)-9 on primary cultures of rat basal forebrain cholinergic neurons (BFCN) obtained at embryonic day 17. FGF-9 enhanced survival of AChE-positive neurons, increased their mean soma size, and up-regulated their choline acetyltransferase (ChAT) activity. The ChAT-promoting effect of FGF-9 was approximately as potent as that of nerve growth factor (NGF) and was greater than those of basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), or glia-derived neurotrophic factor (GDNF). Simultaneous addition of FGF-9 and NGF induced extremely high ChAT levels, suggesting that FGF-9 and NGF may enhance cholinergic properties in BFCN via different pathways that can act synergistically. In immunocytochemical and in situ hybridization studies in cultured cells and also in sections of adult rat brain, BFCN showed cytoplasmic immunostaining for FGF-9 and expressed FGF-9 messenger RNA; thus, we concluded that FGF-9 acts on BFCN in an autocrine and/or paracrine manner. Although effective delivery of exogenous FGF-9 into the central nervous system remains a problem to be solved, FGF-9 may be a promising candidate for therapeutic trials in Alzheimer disease.
Kanda
T
T
Department of Neurology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, 113-8519, Tokyo, Japan. t-kanda.nuro@med.tmd.ac.jp
Iwasaki
T
T
Nakamura
S
S
Kurokawa
T
T
Ikeda
K
K
Mizusawa
H
H
D000818:Animals; D019898:Autocrine Communication; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004357:Drug Synergism; D004622:Embryo, Mammalian / Q000502:physiology; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D017403:In Situ Hybridization; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019899:Paracrine Communication; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology / Q000201:enzymology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C496461:Fgf9 protein, rat; D051525:Fibroblast Growth Factor 9; D006133:Growth Substances; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase