Dopamine transporter knock-out mice are hypersensitive to 3-nitropropionic acid-induced striatal damage.
Evidence suggests that dopamine is involved in the modulation of striatal excitotoxic processes. To further investigate this issue, we studied the effects of systemic 'low-dose' (total dose, 340 mg/kg in 7 days) 3-nitropropionic acid (3-NP) intoxication in dopamine transporter knock-out mice (DAT-/-) compared to wildtype (DAT+/+) mice. Systemic 'low-dose' 3-NP induced a significant impairment in a rotarod task only in DAT-/- mice. Histopathology also demonstrated a significant reduction of the striatal volume (-7%, P < 0.05), neuronal density (-12.5%, P < 0.001) and absolute number estimates of striatal neurons (-11.5%, P < 0.001) in DAT-/- compared to DAT+/+ mice, with increased glial activation, independent of the degree of succinate dehydrogenase inhibition. These findings strengthen the hypothesis for dopamine modulation of excitotoxicity within the nigrostriatal system.
Fernagut
Pierre-O
PO
Laboratoire de Neurophysiologie, UMR-CNRS 5543. 146, rue Léo Saignat, Université Victor Segalen Bordeaux2, 33076 Bordeaux Cedex, France.
Diguet
Elsa
E
Jaber
Mohamed
M
Bioulac
Bernard
B
Tison
François
F
D000818:Animals; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003292:Convulsants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000235:genetics*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D017072:Neostriatum / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins; D009434:Neural Pathways / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D009498:Neurotoxins / Q000494:pharmacology; D009574:Nitro Compounds; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D011422:Propionates / Q000494:pharmacology; D013378:Substantia Nigra / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D003292:Convulsants; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; C493215:Slc6a3 protein, mouse; C015392:3-nitropropionic acid; D004298:Dopamine