3-Nitropropionic acid induces cell death and mitochondrial dysfunction in rat corticostriatal slice cultures.
Exposure of organotypic rat corticostriatal slice cultures to the mitochondrial toxin 3-nitropropionic acid (3-NP) resulted in concentration-dependent loss of cresylviolet-stained cells and increase of lactate dehydrogenase and lactate efflux into the culture medium, indicators for cell death and metabolic activity in the slices, respectively. The involvement of apoptosis in these slices was suggested by using the terminal transferase-mediated biotinylated-UTP nick end-labeling (TUNEL) technique, and immunohistochemistry for the apoptosis-related markers Bax and Bcl-2. In 3-NP-exposed slices, TUNEL-positive cells were observed in both the striatum and the cortex but in different forms: striatal neurons were either diffusely stained or showed nuclear fragmentation, cortical neurons only exhibiting nuclear fragmentation. In 3-NP-exposed slices, the pro-apoptotic protein Bax was abundantly expressed, whereas the anti-apoptotic protein Bcl-2 was not expressed in striatal neurons. We suggest that both apoptosis and necrosis are involved in the 3-NP-treated slices, apoptosis as well as necrosis in the striatum and apoptosis in the cortex.
Vis
José C
JC
321 Department of Neurology, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
de Boer-van Huizen
Roelie T
RT
Verbeek
Marcel M
MM
de Waal
Rob M W
RM
ten Donkelaar
Hans J
HJ
Kremer
Berry
B
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D003292:Convulsants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D008928:Mitochondria / Q000187:drug effects*; D009336:Necrosis; D009410:Nerve Degeneration / Q000139:chemically induced; D009574:Nitro Compounds; D009924:Organ Culture Techniques; D011422:Propionates / Q000494:pharmacology*; D051381:Rats
D003292:Convulsants; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid