Age-associated changes in the dopamine synthesis as determined by GTP cyclohydrolase I inhibitor in the brain of senescence-accelerated mouse-prone inbred strains (SAMP8).
Our objective in this study was to elucidate the mechanism underlying the decrease in dopamine (DA) levels in the brain with ageing We administered 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I to senescence-accelerated mouse-prones (SAMP8), to inhibit DA and serotonin syntheses, and following immunohistochemical staining, analyzed the immunoreactive intensities (IR-Is) for DA in the nigrostriatal dopaminergic neurons by microphotometry. The DA-IR-Is in the substantia nigra pars compacta and neostriatum of young mice (2 months old) reached a minimal value 3 h after DAHP administration and returned to the control value 12 h after the administration. However, in aged mice (10 months old), the minimal value was reached 6 h after the administration and the value remained at approximately 70 and 80% of the control value at 24 and 72 h, respectively, after DAHP administration. The results suggest that DA turnover is lower in aged mice than in young mice.
Karasawa
N
N
Department of Anatomy, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan.
Yamawaki
Y
Y
Nagatsu
T
T
Kawase
T
T
Nishiyama
K
K
Watanabe
K
K
Onozuka
M
M
Nagatsu
I
I
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006136:GTP Cyclohydrolase / Q000037:antagonists & inhibitors*; D007042:Hypoxanthines / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017072:Neostriatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000096:biosynthesis; D013378:Substantia Nigra / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007042:Hypoxanthines; D012701:Serotonin; D006136:GTP Cyclohydrolase; C017202:2,4-diaminohypoxanthine; D004298:Dopamine