NGF, BDNF and NT-5, but not NT-3 protect against MPP+ toxicity and oxidative stress in neonatal animals.
A growing body of evidence suggests that neurotrophic factors can protect neurons against neuronal death. In the present study we examined whether systemic administration of members of the neurotrophin family, nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and neurotrophin 5 (NT-5) and basic fibroblast growth factor (bFGF) could protect against 1-methyl-4-phenylpyridinium (MPP+) induced striatal damage in neonatal rats. Systemic administration of NGF, BDNF and NT-5 produced significant neuroprotective effects, whereas NT-3 was ineffective. Systemic administration of bFGF had significant neuroprotective effects as assessed by T2-weighted magnetic resonance imaging and measurements of n-acetylaspartate and lactate using chemical shift magnetic resonance imaging. Systemic administration of NGF, BDNF and bFGF, but not NT-3 attenuated MPP+ induced increases in hydroxyl radical generation as assessed by the conversion of salicylate to 2,3- or 2,5-dihydroxybenzoic acid (DHBA). These results show that systemic administration of several neurotrophins and bFGF can attenuate neuronal damage induced by chemical hypoxia in vivo by a mechanism which may involve attenuation of oxidative stress.
Kirschner
P B
PB
Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114, USA.
Jenkins
B G
BG
Schulz
J B
JB
Finkelstein
S P
SP
Matthews
R T
RT
Rosen
B R
BR
Beal
M F
MF
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology*; D020933:Neurotrophin 3; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; C071951:neurotrophin 5; D015655:1-Methyl-4-phenylpyridinium