Evidence of deprenyl-insensitive apoptosis of nigral dopamine neurons during development.
Apoptosis of dopamine neurons occurs naturally in the substantia nigra during development, culminating in approximately 30% loss of these cells during the perinatal period. Deprenyl, independent of its monoamine oxidase (MAO)-B inhibitory properties, can prevent dopamine neuronal apoptosis in models of neurodegeneration. Our current study demonstrate that apoptotic death of dopamine neurons during development is insensitive to daily treatment of pregnant mothers and then newborns with deprenyl (0.1, 1, or 10 mg/kg). This result is not due to poor crossing of the placental and blood-brain barriers, since deprenyl caused a dose-dependent inhibition of brain MAO-B activity in pups at birth. Determining the pathway(s) leading to deprenyl-insensitive apoptosis of nigral dopamine neurons in development may shed light on mechanisms underlying the premature death of dopamine neurons in neurodegenerative disorders.
Groc
L
L
William T. Gossett Neurology Laboratories, Henry Ford Hospital, Detroit, MI, USA. l1groc1@hfhs.org
Levine
R A
RA
Foster
J A
JA
Normile
H J
HJ
Weissmann
D
D
Bezin
L
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D004298:Dopamine / Q000502:physiology; D005260:Female; D008995:Monoamine Oxidase / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D012642:Selegiline / Q000494:pharmacology*; D013378:Substantia Nigra / Q000166:cytology* / Q000196:embryology*
D018696:Neuroprotective Agents; D012642:Selegiline; D008995:Monoamine Oxidase; D004298:Dopamine