Effects of mitochondrial toxins on the brain amino acid concentrations.
In the pathogenesis of Parkinson's disease and Huntington's disease excitotoxicity may play an important role. The common toxin model for Parkinson's disease is MPTP, while for Huntington's disease it is 3-NP. These toxins inhibit the mitochondrial respiratory chain, resulting in an energy deficit. In the central nervous system, the amino acids act as neurotransmitters and neuromodulators. The energy deficit caused by these neurotoxins may alter the concentrations of amino acids. Thus, it can be claimed that the aminoacidergic neurotransmission can be changed by neurotoxins. To test this hypothesis we studied the amino acid concentrations in different brain regions following MPTP or 3-NP administration. The two toxins were found to produce similar changes. We detected marked decreases in most of the amino acid concentrations in the striatum and in the cortex, while the levels in the cerebellum increased significantly. The decreased amino acid levels can be explained by the reduced levels of ATP produced by these neurotoxins. In the cerebellum, where there is no detectable ATP loss, the elevated amino acid levels may reflect a compensation of the altered neurotransmission.
Klivenyi
Peter
P
Department of Neurology, University of Szeged, P.O.B. 427, Szeged, H-6701, Hungary.
Kekesi
Katalin A
KA
Hartai
Zsuzsanna
Z
Juhasz
Gabor
G
Vecsei
Laszlo
L
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism / Q000494:pharmacology; D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006816:Huntington Disease / Q000378:metabolism; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology; D009574:Nitro Compounds / Q000378:metabolism / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism; D011422:Propionates / Q000378:metabolism / Q000494:pharmacology
D000596:Amino Acids; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C015392:3-nitropropionic acid