6R-L-erythro-5,6,7,8-tetrahydrobiopterin is involved in brain vulnerability of senescence-accelerated mouse during the processes of aging.
The effects of age on the dopamine (DA) turnover and 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4), a cofactor for monooxygenases, were investigated in the striatum and midbrain of the senescence accelerated mouse (SAM) at 6, 12 and 15 months old. 6R-BH4 and DA levels were decreased significantly in the striatum of 15-month-old SAM-P/1 (senescence accelerated prone) mice. At 12 months old, DA level was decreased significantly in the striatum of SAM-P/1 compared with SAM-R/1 (senescence accelerated resistant) mice. The reduction of striatal DA level was shown to be related to the depletion of 6R-BH4 in the striatum during the processes of aging. Age-related decreases in striatal dopamine function occurred in SAM-P/1 mice earlier than in the SAM-R/1 mice. The striatal [DOPAC]/[DA] ratio, as the index of DA turnover, was increased significantly in the 15-month-old SAM-P/1 mice. On the other hand, the DA, 6R-BH4 levels and the ratio of [DOPAC]/[DA] did not show any changes in the midbrain of SAM-P/1 and SAM-R/1 during the processes of aging. It was suggested that brain vulnerability with aging may be associated with the levels of 6R-BH4.
Yoshimoto
K
K
Department of Legal Medicine, Kyoto Prefectural University of Medicine, Japan.
Yoshida
T
T
Hirano
A
A
Ueda
S
S
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism; D005838:Genotype; D008297:Male; D008636:Mesencephalon / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D017072:Neostriatum / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000975:Antioxidants; D015102:3,4-Dihydroxyphenylacetic Acid; D001708:Biopterins; C022133:3,4-dihydroxybenzylamine; D014446:Tyrosine 3-Monooxygenase; C003402:sapropterin; D004298:Dopamine