Studies on the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57 BL/6 mice. Comparison with three other strains of mice

̈m, Erik Sunstro; ̈mberg, Ingrid Stro; Tsutsumi, Tetsuyuki; Olson, Lar̀s; Jönsson, G

doi:10.1016/0006-8993(87)90986-3

Cited by 195 publications

(88 citation statements)

References 27 publications

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“…3). Despite overall decreases in DA and DOPAC concentrations, a similar increase in the ratio of DOPAC/DA concentrations in striatum following high doses of MPTP administered to mice has been previously reported (9,30). Panels D to F of Fig.…”

Section: Estimation Of Relative Monoamine Concentrations In Survivingsupporting

confidence: 82%

“…Furthermore, the DOPAC/DA ratio per average remaining TH + neuron (panel F) shows a continual increase throughout the life span, thereby suggesting that the remaining SNc neurons increase their turnover and release of DA as the animals age. Although other studies had reported decreasing striatal DA concentrations with increasing MPTP dosages in the mouse (2,8,12,19,20,30), we found at 20 days after MPTP treatment, striatal DOPAC concentrations fell less precipitously than the DA levels resulting in an increased DOPAC/DA ratio for MPTP dosages exceeding 100 mg/kg (panels A-C, Fig. 3).…”

Section: Estimation Of Relative Monoamine Concentrations In Survivingcontrasting

confidence: 75%

“…However, the TH + SNc neurons remaining after MPTP-induced axonal damage may have been at varying stages of a repair/compensatory sequence, such that maximal induction of DA synthesis may not have occurred in all neurons [see (32) for a more detailed discussion of axonal repair mechanisms and return of TH + soma following MPTP damage of dopaminergic retinal amacrine cells]. A time-dependent increase in DA metabolism in SNc neurons surviving 6-OHDA or MPTP exposure has been previously demonstrated (30,35). In these former studies, striatal DA levels did not reach control values even when animals had been allowed to survive for greater periods of time posttoxic exposure; however, the estimated degree of SNc loss (usually greater than 80-90%) exceeded that observed for the highest dose of MPTP used in this present study.…”

Section: Post Synaptic Potentialmentioning

confidence: 97%

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Increased dopamine synthesis in aging substantia nigra neurons

Greenwood

Tatton

Seniuk

et al. 1991

Neurobiology of Aging

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Section: Estimation Of Relative Monoamine Concentrations In Survivingsupporting

confidence: 82%

Section: Estimation Of Relative Monoamine Concentrations In Survivingcontrasting

confidence: 75%

Section: Post Synaptic Potentialmentioning

confidence: 97%

See 1 more Smart Citation

Increased dopamine synthesis in aging substantia nigra neurons

Greenwood

Tatton

Seniuk

et al. 1991

Neurobiology of Aging

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“…Consistent with previous reports (Heikkila et al, 1984;Sundstrom et al, 1987), systemic administration of MPTP markedly decreased striatal levels of DA, DOPAC, and 3-MT without affecting 5-HT. Administration of SL25.1131 in MPTP-treated mice failed to increase DA but increased 5-HT and 3-MT and decreased DOPAC levels.…”

Section: Discussionsupporting

confidence: 92%

SL25.1131 [3(S),3a(S)-3-Methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a New, Reversible, and Mixed Inhibitor of Monoamine Oxidase-A and Monoamine Oxidase-B: Biochemical and Behavioral Profile

Aubin

Barnéoud²,

Carter³

et al. 2004

J Pharmacol Exp Ther

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SL25.1131 [3(S),3a(S)-3 -methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one] is a new, nonselective, and reversible monoamine oxidase (MAO) inhibitor, belonging to a oxazoloquinolinone series. In vitro studies showed that SL25.1131 inhibits rat brain MAO-A and MAO-B with IC 50 values of 6.7 and 16.8 nM and substratedependent K i values of 3.3 and 4.2 nM, respectively. In ex vivo conditions, the oral administration of SL25.1131 induced a dose-dependent inhibition of MAO-A and MAO-B activities in the rat brain with ED 50 values of 0.67 and 0.52 mg/kg, respectively. In the rat brain, duodenum, and liver, the inhibition of MAO-A and MAO-B by SL25.1131 (3.5 mg/kg p.o.) was reversible, and the recovery of MAO-A and MAO-B activities was complete 16 h after administration. SL25.1131 (3.5 mg/kg p.o.) increased tissue levels of dopamine (DA), norepinephrine, and 5-hydroxytryptamine and decreased levels of their deaminated metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindolacetic acid. In mice, SL25.1131 induced a dose-dependent potentiation of 5-hydroxytryptophan-induced tremors and phenylethylamine-induced stereotypies with ED 50 values of 0.60 and 2.8 mg/kg p.o., respectively. SL25.1131 was able to reestablish normal striatal dopaminergic tone and locomotor activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice. In addition, when coadministered with L-DOPA, SL25.1131 increased the available DA in the striatum and the duration of L-DOPA-induced hyperactivity. The duration of the effect of L-DOPA on circling behavior in 6-hydroxydopamine-lesioned rats was also increased. The neurochemical profile of SL25.1131 demonstrates that this compound is a mixed, potent, and reversible MAO-A/B inhibitor in vitro, in vivo, and ex vivo. SL25.1131 has therapeutic potential as a symptomatic treatment during the early phase of Parkinson's disease and as an adjunct to L-DOPA therapy during the early and late phases of the disease.Monoamine oxidase (MAO) deaminates monoamine neurotransmitters as well as exogenous amines. Two isoforms of MAO have been described in mammalian tissue, namely, MAO-A and MAO-B, which exhibit different substrate profiles, respond differently to selective inhibitors, and are present in different cellular and subcellular locations. MAO-A preferentially deaminates 5-hydroxytryptamine (serotonin) (5-HT) and norepinephrine (NE) and is selectively inhibited by clorgyline (Johnston, 1968), whereas MAO-B is selectively inhibited by L-deprenyl and preferentially deaminates phenylethylamine (PEA) and benzylamine (Knoll and Magyar, 1972). Dopamine (DA) and tyramine (TYR) are metabolized by both enzyme isoforms (for review, see StrolinBenedetti and Dostert, 1985).Article, publication date, and citation information can be found at

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“…The administration of MPTP induces Parkinsonlike signs in rodents and is an often used model of PD (120). When given to mice, Acufia-Castroviejo et al (84) reported a loss of immunoreactive tyrosine hydroxylase activity in the striatum, evidence of neural damage in several brain areas, and increased lipid peroxidation in the hippocampus and striatum within 4 hours.…”

Section: Age-related Disease Models In Which Melatonin Has Been Testedmentioning

confidence: 99%

Aging and oxygen toxicity: Relation to changes in melatonin

Reíter

1997

AGE

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Melatonin (N-acetyl-5-methoxytryptamine) is a chemical mediator produced in the pineal gland and other sites in the body. The melatonin found in the blood is derived almost exclusively from the pineal gland. Since the pineal synthesizes melatonin primarily at night, blood levels of the indole are also higher at night (5-15 fold) than during the day. Some individuals on a nightly basis produce twice as much melatonin as others of the same age. Throughout life, the melatonin rhythm gradually wanes such that, in advanced age, melatonin production is usually at a minimum. Melatonin was recently found to be a free radical scavenger and antioxidant. It has been shown, in the experimental setting, to protect against both free radical induced DNA damage and oxidative stress-mediated lipid peroxidation. Pharmacologically, melatonin has been shown to reduce oxidative damage caused by such toxins as the chemical carcinogen safrole, carbon tetrachloride, paraquat, bacterial lipopolysaccharide, kainic acid, 8-aminolevulinic and amyloid 13 peptide of AIzheimer's disease as well as a model of Parkinson's disease involving the drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Additionally, the oxidative damage caused by agents such as ionizing radiation and excessive exercise is reduced by melatonin. Since free radical-induced molecular injury may play a significant role in aging, melatonin's ability to protect against it suggests a potential function of melatonin in deferring aging and agerelated, free radical-based diseases. Besides its ability to abate oxidative damage, other beneficial features of melatonin may be important in combating the signs of aging; these include melatonin's immune-stimulating function, its sleep-promoting ability, its function as an anti-viral agent, and general protective actions at the cellular level. Definitive tests of the specific functions of physiological levels of melatonin in processes of aging are currently being conducted.

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Studies on the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57 BL/6 mice. Comparison with three other strains of mice

Cited by 195 publications

References 27 publications

Increased dopamine synthesis in aging substantia nigra neurons

Increased dopamine synthesis in aging substantia nigra neurons

SL25.1131 [3(S),3a(S)-3-Methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a New, Reversible, and Mixed Inhibitor of Monoamine Oxidase-A and Monoamine Oxidase-B: Biochemical and Behavioral Profile

Aging and oxygen toxicity: Relation to changes in melatonin

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