Brain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain.
Cell culture studies with dissociated primary cultures from embryonic rat brain revealed that brain-derived neurotrophic factor (BDNF) promotes the developmental differentiation of both basal forebrain cholinergic and mesencephalic dopaminergic neurons. These studies suggested that, in the adult brain, BDNF may be able to protect cholinergic and dopaminergic neurons from degenerative changes induced by axotomy, similar to the known protective action of NGF in cholinergic neurons. Testing this hypothesis, we found that intraventricular administration of recombinant human BDNF (rhBDNF) to adult rats with transections of the fimbria significantly reduces axotomy-induced degenerative changes of the cholinergic cells in the basal forebrain. No such effect was seen on the dopaminergic neurons of the ventral mesencephalon after transection of their axons ascending in the medial forebrain bundle. Injected in equal amounts, rhBDNF and recombinant human NGF had quantitatively different effects on the cholinergic neurons. BDNF sustained only part of the population of cholinergic neurons affected by the lesion, whereas the entire population was protected by NGF treatment.
Knüsel
B
B
Division of Neurogerontology, Andrus Gerontology Center, University of Southern California, Los Angeles 90089.
Beck
K D
KD
Winslow
J W
JW
Rosenthal
A
A
Burton
L E
LE
Widmer
H R
HR
Nikolics
K
K
Hefti
F
F
D000818:Animals; D001369:Axons / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor; D002794:Choline / Q000502:physiology*; D003714:Denervation; D004298:Dopamine / Q000502:physiology; D005260:Female; D009410:Nerve Degeneration / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D002794:Choline; D004298:Dopamine