Dramatic brain aminergic deficit in a genetic mouse model of phenylketonuria.
Clinical data suggest that brain catecholamines and serotonin are deficient in phenylketonuria (PKU), an inherited metabolic disorder that causes severe mental retardation and neurological disturbances. To test this hypothesis, brain tissue levels of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT) and their metabolites were evaluated in the genetic mouse model of PKU (Pah(enu2)). Results indicated a significant reduction of 5-HT levels and metabolism in prefrontal cortex (pFC), cingulate cortex (Cg), nucleus accumbens (NAc), caudate putamen (CP), hippocampus (HIP) and amygdala (AMY). NE content and metabolism were reduced in pFC, Cg, AMY and HIP. Finally, significantly reduced DA content and metabolism was observed in pFC, NAc, CP and AMY. In pFC, NAc and CP there was also a marked reduction of DA release.
Puglisi-Allegra
S
S
Dipartimento di Psicologia, Università La Sapienza, Rome, Italy.
Cabib
S
S
Pascucci
T
T
Ventura
R
R
Cali
F
F
Romano
V
V
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D010661:Phenylketonurias / Q000235:genetics / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism; D011699:Putamen / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D015306:Biogenic Monoamines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; C001746:3-methoxytyramine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid