Brain-derived neurotrophic factor expression in the substantia nigra does not change after lesions of dopaminergic neurons.
Progressive and irreversible loss of specific neuronal cell populations is commonly seen in chronic neurodegenerative diseases such as Parkinson's disease (PD). Evidence is accumulating that apoptosis is a crucial cellular event responsible for the dysfunction and death of neurons in this disease. Thus, limiting apoptosis may prevent disease pathogenesis. Key to reducing apoptosis is the discovery of neuroprotective compounds that can be given to patients to minimize neuronal damage. In this manuscript, we reviewed the rationale of using an experimental strategy to provide neurotrophic support to injured neurons. Such rationale includes the increase of endogenous production of brain-derived neurotrophic factor (BDNF). BDNF is a potent inhibitor of apoptosis-mediated cell death and neurotoxin-induced degeneration of dopaminergic neurons. However, availability of BDNF may be reduced when dopaminergic neurons degenerate. Therefore, in this work, we have used several well-established neurotoxins for dopaminergic neurons, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 6-OH-dopamine (6-OHDA), and the HIV protein gp120, to examine whether degeneration of nigrostriatal fibers alters BDNF expression. Our data show that these neurotoxins do not decrease the levels of BDNF in the substantia nigra, suggesting that up-regulation of BDNF synthesis by pharmacological means may be a viable therapy to slow down the progress of PD and other neurodegenerative diseases.
Mocchetti
Italo
I
Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA. moccheti@georgetown.edu
Bachis
Alessia
A
Nosheny
Rachel L
RL
Tanda
Gianluigi
G
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology*; D051381:Rats; D013378:Substantia Nigra / Q000473:pathology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009498:Neurotoxins; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine