Transplantation of NGF secreting primary monocytes counteracts NMDA-induced cell death of rat cholinergic neurons in vivo.
Cholinergic neurons of the basal forebrain degenerate in Alzheimer's disease. Nerve growth factor (NGF) is so far the most potent molecule to counteract this neurodegeneration; however, the delivery of NGF into the brain is very difficult. The aim of the present study was to observe, if transplanted primary monocytes secreting NGF may counteract N-methyl-D-aspartate (NMDA)-induced cell death of cholinergic neurons of the basal nucleus of Meynert (nBM) in vivo. Monocytes were purified by indirect magnetic separation from rat blood. Recombinant NGF was introduced into cells using the novel protein-delivery reagent BioPORTERtrade mark and secretion of NGF was measured by ELISA. Monocytes secreted approximately 4000 pg NGF/day/1 x 10(6) cells. Injection of monocytes onto organotypic brain slices of the nBM in vitro protected cholinergic neurons against cell death. When monocytes were transplanted in vivo into the lateral ventricle, the cells survived for up to 7 days and counteracted the NMDA-induced cell death of cholinergic neurons. In conclusion, primary monocytes secreting recombinant NGF are useful to deliver NGF directly into the brain.
Zassler
Birgit
B
Laboratory of Experimental Alzheimer Research, Univ. Clinic of Psychiatry, Anichstr. 35, A-6020 Innsbruck, Innsbruck Medical University, Austria.
Humpel
Christian
C
D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D020532:Basal Nucleus of Meynert / Q000166:cytology; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology / Q000601:surgery; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017690:Cell Transplantation / Q000379:methods*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018014:Gene Transfer Techniques; D066298:In Vitro Techniques; D009000:Monocytes / Q000378:metabolism*; D016202:N-Methylaspartate / Q000633:toxicity*; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015703:Antigens, CD; D016202:N-Methylaspartate; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase