BDNF protection of basal forebrain cholinergic neurons after axotomy: complete protection of p75NGFR-positive cells.
To elucidate the role of brain derived neurotrophic factor (BDNF) in the protection of cholinergic neurons in the basal forebrain, recombinant human BDNF and as a positive control, human recombinant nerve growth factor (NGF), were infused for 20 days into the lateral ventricle of adult rats with fimbrial transections. BDNF and NGF administration protected cholinergic basal forebrain cells from degenerative changes after axotomy, as assessed with immunohistochemical analysis of the two cholinergic marker proteins ChAT and p75NGFR. Both BDNF and NGF treatment completely prevent the lesion induced loss of p75NGFR-positive cells in the septal area of animals with fimbrial transections. This finding contrasts with the result obtained with ChAT immunohistochemistry, where BDNF treatment protects only part of the population of neurons which disappear following the transections. These findings are compatible with the view that there is a cascade of events induced in cholinergic neurons by the transections, so that ChAT expression is lost before p75NGFR expression, and that BDNF reduces degenerative events in the entire population of cholinergic neurons, maintaining some of them as p75NGFR-positive but ChAT-negative cells.
Division of Neurogerontology, Andrus Gerontology Center University of Southern California, Los Angeles 90089-0191.
H R
HR
Widmer
B
B
Knüsel
F
F
Hefti
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor; D005260:Female; D009414:Nerve Growth Factors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000502:physiology*; D016548:Prosencephalon / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017475:Receptors, Nerve Growth Factor
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D000109:Acetylcholine