Septal neuron cholinergic and GABAergic functions: differential regulation by basic fibroblast growth factor and epidermal growth factor.
Numerous studies suggest that growth and trophic factors play roles in the development and mature function of brain neurons. Recently, growth factors whose actions were previously characterized on non-neuronal cells have been localized to the brain. We sought to determine whether these factors influence septal cholinergic function. Initially, we defined the effects of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) on septal cholinergic cells in dissociated neuronal culture. Both factors elevated activity of the acetylcholine synthetic enzyme, choline acetyltransferase (CAT). To determine whether the factors acted directly on neurons or whether glia mediated the effects, a mitotic inhibitor, 5-fluorodeoxyuridine (FDUR), was added to the cultures to eliminate dividing glia. The action of EGF was completely blocked by the addition of FDUR. However, bFGF elevated CAT activity even in the presence of FDUR. Consequently, bFGF may regulate septal cholinergic function directly, whereas EGF may affect cholinergic cells indirectly through glia. To determine whether increases in CAT activity reflect increased enzyme activity per neuron or an increase in the number of cholinergic cells, bFGF-treated cultures were stained for acetylcholinesterase (AChE) to determine numbers of cholinergic cells. No differences in AChE-positive cells were noted, suggesting that bFGF increased CAT activity per cholinergic neuron. To determine whether bFGF regulates other populations in the septum, we examined GABAergic neurons by monitoring the activity of glutamic acid decarboxylase (GAD), a GABA synthetic enzyme. Basic FGF significantly increased GAD activity; however, the effect was completely abolished by addition of FDUR. Thus, bFGF may act directly on cholinergic neurons and indirectly on GABA cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Yokoyama
M
M
Department of Neurology, Cornell University Medical College, New York, NY 10021.
Morrison
R S
RS
Black
I B
IB
Dreyfus
C F
CF
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005467:Floxuridine / Q000494:pharmacology; D005865:Gestational Age; D005968:Glutamate Decarboxylase / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005467:Floxuridine; D016222:Fibroblast Growth Factor 2; D005680:gamma-Aminobutyric Acid; D004815:Epidermal Growth Factor; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D000109:Acetylcholine