Stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP+) decreases striatal fructose 2,6-bisphosphate in rats.
The stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP+) into the neostriatum of male rats caused a lesion that resulted in a large dose-dependent loss of striatal fructose 2,6-bisphosphate; initial values were restored 5 days after the treatment. This effect was not protected by systemic administration of MK-801 or by nitroarginine. The content of hexose 6-phosphates and ATP was also reduced by MPP+ treatment, whereas lactate was increased. Biochemical and histological results suggested that MPP+ caused a nonselective cell death, followed by a pronounced astroglial response, parallel to fructose 2,6-bisphosphate recovery. The stereotaxic administration of rotenone showed a different time effect on fructose 2,6-bisphosphate cerebral content, with a significantly faster recovery. These results indicate that cerebral fructose 2,6-bisphosphate may be a sensitive metabolite related to brain damage caused by potent neurotoxins such as MPP+. On the other hand, they show that MPP+ acts in the brain through a quick, strong cytotoxic mechanism, which probably involves mechanisms other than mitochondrial chain blockage.
Espino
A
A
Unitat de Bioquímica, Universitat de Barcelona, Spain.
Tortosa
A
A
Bendahan
G
G
Bartrons
R
R
Calopa
M
M
Ferrer
I
I
Ambrosio
S
S
D015655:1-Methyl-4-phenylpyridinium / Q000008:administration & dosage / Q000494:pharmacology*; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005635:Fructosediphosphates / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006600:Hexosephosphates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000494:pharmacology; D013238:Stereotaxic Techniques; D013997:Time Factors
D000227:Adenine Nucleotides; D005635:Fructosediphosphates; D006600:Hexosephosphates; D012402:Rotenone; D019335:Nitroarginine; D016291:Dizocilpine Maleate; C027652:fructose 2,6-diphosphate; D001120:Arginine; D015655:1-Methyl-4-phenylpyridinium