Insulin-like growth factor II promotes in vitro cholinergic development of mouse septal neurons: comparison with the effects of insulin-like growth factor I.
We investigated the effect of insulin-like growth factors II and I (IGFII and IGFI) on septal primary cultures from mouse embryonic day 15 brains. The addition of IGFII to septal cultures enhanced total choline acetyltransferase (ChAT) activity in a dose-dependent manner. Maximal stimulation of ChAT activity was observed at 10 ng/ml IGFII. The effect of IGFII on ChAT activity was completely blocked by anti-IGFII/M-6-P receptor antibodies, whereas the antisera alone had no effect on the enzyme activity. Double-labeled immunohistochemical studies revealed that most ChAT-positive neurons expressed IGFII/M-6-P receptor immunoreactivity. These results indicate that the trophic effect of IGFII results from the direct action of this molecule through the IGFII/M-6-P receptor in septal cholinergic neurons. IGFI also stimulated ChAT activity, but with less potency than IGFII. Antibodies against the IGFII/M-6-P receptor inhibited approximately 50% of the IGFI response, suggesting that the effect of IGFI is mediated in part by the IGFII/M-6-P receptor. Thus, it appears that IGFII and IGFI are potent trophic factors for central cholinergic neurons and could potentially play a significant role in the differentiation, maintenance and regeneration of these neurons.
Division of Demyelinating Disease and Aging, National Center of Neurology and Psychiatry, Tokyo, Japan.
Y
Y
Konishi
K
K
Takahashi
D H
DH
Chui
R G
RG
Rosenfeld
M
M
Himeno
T
T
Tabira
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D010275:Parasympathetic Nervous System / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D017527:Receptor, IGF Type 2; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D002795:Choline O-Acetyltransferase