Recovery of nucleus basalis cholinergic neurons by grafting NGF secretor fibroblasts.
The effects of nerve growth factor (NGF) secreted from genetically modified fibroblasts was studied in vitro, using dissociated septal cells and in vivo, in rats bearing unilateral cortical devascularizing lesions. Transfected fibroblasts expressing nerve growth factor (NGF) were co-cultured with rat embryonic cholinergic cells of the septal region. This in vitro system showed that NGF secretor cells produce biologically active NGF, as determined by increasing choline acetyltransferase (ChAT) activity in septal culture after seven days. The potential therapeutic value of applying grafts of transfected fibroblasts expressing NGF in the model of retrograde atrophy of cholinergic neurons of the nucleus basalis magnocellularis (NBM) was assessed following partial devascularizing lesions of the cerebral cortex. We observed an increase in ChAT activity in the remaining cortex and a partial protection of the ipsilateral NBM, as determined by morphometric and biochemical studies.
Piccardo
P
P
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Maysinger
D
D
Cuello
A C
AC
D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000502:physiology*; D002460:Cell Line; D002540:Cerebral Cortex / Q000098:blood supply; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology / Q000637:transplantation*; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D014162:Transfection
D009414:Nerve Growth Factors; D002795:Choline O-Acetyltransferase