Axotomy-dependent stimulation of choline acetyltransferase activity by exogenous mouse nerve growth factor in adult rat basal forebrain.
Transection of the adult rat dorsal fornix and fimbria (F-F) induced a sensitivity of the cholinergic neurons in the medial septum and diagonal band (MS/DB) to exogenous mouse nerve growth factor (mNGF). Continuous infusion of mNGF for two weeks after complete unilateral F-F aspiration resulted in a stimulation of choline acetyltransferase (ChAT)-specific activity in precise micro-dissections of the MS/DB ipsilateral to the transection to a level that was 200% higher than that measured in normal adult animals. This supranormal stimulation of ChAT activity reached plateau levels after 10 days of NGF infusion and was dose-dependent with an E.D.50 equal to 120 ng/day. Administration of mNGF had no effect on the ChAT activity in the MS/DB of normal animals or animals with a unilateral transection of only the supracallosal dorsal septo-hippocampal pathway. Partial transection experiments indicated that a predominent pathway for cholinergic neurons potentially sensitive to exogenous mNGF runs in the paramedian F-F. Administration of mNGF also induced a stimulation of ChAT activity in dissections of the caudate-putamen both ipsi- and contralateral to the infusion cannula. This indicates that unlike the cholinergic projection neurons of the MS/DB, adult cholinergic striatal interneurons are sensitive to exogenous NGF without prior axotomy.
Williams
L R
LR
CNS Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
Jodelis
K S
KS
Donald
M R
MR
D000818:Animals; D001369:Axons / Q000502:physiology*; D002421:Caudate Nucleus / Q000201:enzymology; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003714:Denervation; D004027:Diencephalon / Q000201:enzymology*; D004210:Dissection; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000201:enzymology; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D011699:Putamen / Q000201:enzymology; D051381:Rats; D013687:Telencephalon / Q000201:enzymology*
D009414:Nerve Growth Factors; D002795:Choline O-Acetyltransferase