SummaryThe effect of dimethylsulfoniopropionate (DMSP) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease (PD) of mice was examined for 5 d. The distilled water (the control group) and the DMSP solution at 5ϫ10 Ϫ4 M (the DMSP group) were supplemented ad libitum to six mice each in two groups for 2 wk. An appropriate amount of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) solution (20 mg/kg body wt) was then intraperitoneally injected into all the test mice once a day initially for 3 d, which definitely made the control mice similar to the PD-model mice. The moving ability (running power) of the mice in both groups was measured using an automatic Wheel Running Instrument. The immobility duration of the upside-down mice in both groups was estimated by a newly developed polygraph (RMP-6008M, Nihon Koden Co., Ltd., Japan). The results indicated that the mice in the DMSP group showed a stronger moving ability and a shorter immobility duration compared to the mice in the control group during the experimental period. Furthermore, the amounts of catecholamines (dopamine and norepinephrine) in the brains except for the cerebellums of all the test mice were estimated 2 d after the last MPTP injection, which demonstrated that the brains of the mice in the DMSP group accumulate larger amounts of catecholamines, especially dopamine, than them in the control group. Accordingly, the administration of low concentrations of DMSP proved to prevent and/or ameliorate the decreased mobility and the typical immobility (Akinesia) of the MPTP-induced PD-model mice probably due to increased amounts of dopamine in the brains of the DMSP group mice.

SummaryThe combined effects of dimethylsulfoniopropionate (DMSP) (10 Ϫ 3 , 10 Ϫ 4 and 10 Ϫ 5 M ) with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (5 ng/mL) and the nerve growth factor (NGF) (5 ng/mL) on the outgrowth and elongation of neurites from pheochromocytoma (PC12) cells were examined on RPMI medium containing fetal bovine serum and horse serum with penicillin and streptomycin in collagen-coated dishes for 5 d. The growth was higher in increasing order of the DMSP (10 Ϫ 3 M ), MPTP and NGF, the DMSP (10 Ϫ 5 M ), MPTP and NGF, the MPTP and NGF group and the control group up to 3 d, but not in the NGF and the DMSP (10 Ϫ 4 M ), MPTP and NGF groups. The growth in all the experimental groups showed plateaus from days 4 to 5. The appearance of neurites from the cells in all the groups showed maxima on the 3rd day. The administration of NGF significantly stimulated the outgrowth of neurites from the cells, while the supplementation of MPTP noticeably inhibited the appearance of neurites even in the presence of NGF up to 5 d. However, the addition of DMSP (10 Ϫ 3 and 10 Ϫ 4 M ) to the latter group completely prevented the inhibition of the MPTP. These facts were significantly supported by the photographs of neurite-bearing cells on the 3rd day and also by the photometric analyses examining the reaction of MPTP to DMSP, NGF or Collagen IV.

SummaryThe induction of Parkinson's disease (PD) in senescence-accelerated mice (SAMP8) by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the effects of dimethylsulfoniopropionate (DMSP) on induced PD model mice of SAMP8 were investigated for 5 wk. After many trials, the tail suspension test determining the PD symptoms indicated that an appropriate amount of MPTP clearly raises the SAMP8 mice to the PD-model mice. Moreover, DMSP administration to the PD-SAM model mice proved to completely reduce the PD symptoms in the mice and to accumulate large amounts of norepinephrine, dopamine and dioxyphenylacetate in the mouse brains without cerebellums. These results suggest that catecholamines accumulated in large quantities by the supplementation of DMSP to the double-diseased mice, PD-SAMP8 model mice, completely ameliorated the PD symptoms in these model mice. Key Words dimethylsulfoniopropionate, Parkinson's disease, senescence-accelerated mice, catecholamines A tertiary sulfonium compound, dimethylsulfoniopropionate (DMSP), is found in marine animals, especially green sea algae in large amounts ( 1 ), and has been customarily ingested in large and small amounts by a number of people in Japan for many years ( 2 ). We have examined the effects of DMSP on aquatic and terrestrial animals and obtained a variety of noticeable results ( 3 -9 ). In contrast, Parkinson's disease (PD) has proven to principally cause a deficiency in dopamine in the substantia nigra of the brain and sympathetically degenerates and/or degrades the dopaminergic-, norepinephrinergic-, and cholinergic-nervous systems in the brains, resulting in dementia in humans ( 10 -12 ). However, L-dopa does not completely recover the symptoms of PD ( 11 ), although L-dopa is proven to be the most effective among all the drugs used for curing this disease to date ( 11 ). We then examined the effects of DMSP on the PD-model mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP), which indicated that addition of DMSP to the PD-model mice induced from C57BL6 mice effectively ameliorates the characteristic PD symptoms of PD-model mice elicited by MPTP ( 13 ). We further attempted to examine whether or not MPTP can induce parkinsonism in senescence-accelerated mice (SAM)P8 and whether DMSP exerts any effect on the PD-model mice of SAMP8, whose brains exhibit the characteristic properties of early aging (i.e., loss of learning and memory) ( 14 ). Materials and MethodsDMSP was synthesized and purified to 99.8% purification (from element analysis) ( 3 ). 3,4-Dioxyphenylacetic acid (DOPAC) was obtained from Sigma-Aldrich Co., Ltd., Japan. All other chemicals were of the best available quality ( 13 ). The SAMP8 male mice were kind gifts from emeritus Prof. MD. Takeda T. in Kyoto University. The rearing conditions were the same as those in the previous report ( 13 ), except for the following experimental conditions. The twenty mice were divided into two groups, one fed distilled water (the control group) and the other DMSP solution at 5 ϫ 10 Ϫ 4 M...

SummaryMechanisms of riboflavin oversynthesis in a high flavinogenic mold, Eremoth ecium ashbyii, were examined in relation to growth, riboflavin formation and related syn thases, and medium pH with increasing culture periods. Growth reached maximum at 1dand then decreased, riboflavin formation proceeded rapidly up to 5d and approached al most a plateau region. The medium pH reached minimum at 1d and thereafter fairly rap idly increased until 3d, then gradually increased to 7d after cultivation. The crude enzyme solution from the mycelia at specified culture periods was run through a column of Sepha dex G-200, indicating two riboflavin synthase activities on the chromatogram. The fluctua tion of the growth and the specific activities of the two enzymes were examined with in creasing culture periods, which showed that the heavy enzyme may be a constitutive one and that the light enzyme may be concerned with the oversynthesis of riboflavin in E. ash byil. The heavy enzyme was then purified by 49-fold after dialysis of the ammonium sulfate precipitate by a series of column chromatographies with Sephadex G-200, hydroxyapatite, DEAE-Sepharose A-50 and DEAE-cellulose. The purified enzyme which was treated with weak alkaline solution was broken into the light enzyme, showing two bands on an acryl amide disc gel electrophoresis. The relation of the heavy and the light enzymes to the over synthesis of riboflavin in E, ashbyii was discussed.