Reduced MPTP toxicity in noradrenaline transporter knockout mice

Rommelfanger, Karen S.; Weinshenker, David; Miller, Gary W.

doi:10.1111/j.1471-4159.2004.02785.x

Cited by 74 publications

(60 citation statements)

References 60 publications

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“…Our previous experiments indicated that the supplementation of DMSP accelerates the swimming power and the growth in fish (15) and the mobility in rats (7) and simultaneously accumulates norepinephrine in their brains. Moreover, there are reports that the destruction of norepinephrine terminals in brains decreases the locomotion activity in MPTP-treated mice (16) and that noradrenalin modulates the MPTP toxicity in norepinephrine transporter knockout mice (17). These facts may imply that the elevation of norepinephrine amounts also functions so as to increase the running power and to shorten the immobility duration in the PD-model mice of the DMSP group in the present experiments.…”

Section: Discussionsupporting

confidence: 50%

Ameliorating Effect of Dimethylsulfoniopropionate on the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson's Disease of Mice

Nakajima

Minematsu

2006

J Nutr Sci Vitaminol

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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.

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Section: Discussionsupporting

confidence: 50%

Ameliorating Effect of Dimethylsulfoniopropionate on the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson's Disease of Mice

Nakajima

Minematsu

2006

J Nutr Sci Vitaminol

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“…Moreover, a recent report indicates that  2 -adrenoceptor agonists inhibit dopaminergic neuron loss induced by LPS in vitro and in vivo (Qian et al, 2011). In further support of the idea that NRIs may be successful in ameliorating the progression of PD, it has been demonstrated that NA transporter knockout mice display reduced toxicity to MPTP (Rommelfanger et al, 2004). In this regard, both NRIs and 2-adrenoceptor agonists are lipophillic compounds and readily penetrate the CNS.…”

Section: 2-adrenoceptor Agonistsmentioning

confidence: 82%

Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease

Collins¹,

Toulouse²,

Connor³

et al. 2012

Neuropharmacology

254

153

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“…On the basis of our results, we predict that PD patients with genetically low dopamine ␤-hydroxylase activity may have earlier onset or more severe motor symptoms and may be more prone to developing dyskinesias. In addition, we have shown that increasing extracellular NE protects DA neurons from MPTP toxicity (56), which implies that noradrenergic drugs could have dual therapeutic functions, by both preventing the progression of DA-neuron loss in PD and, when combined with L-dopa therapy, alleviating PD-associated motor deficits.…”

Section: Discussionmentioning

confidence: 99%

Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice

Rommelfanger¹,

Edwards

Freeman

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

174

116

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Although Parkinson's disease (PD) is characterized primarily by loss of nigrostriatal dopaminergic neurons, there is a concomitant loss of norepinephrine (NE) neurons in the locus coeruleus. Dopaminergic lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are commonly used to model PD, and although MPTP effectively mimics the dopaminergic neuropathology of PD in mice, it fails to produce PD-like motor deficits. We hypothesized that MPTP is unable to recapitulate the motor abnormalities of PD either because the behavioral paradigms used to measure coordinated behavior in mice are not sensitive enough or because MPTP in the absence of NE loss is insufficient to impair motor control. We tested both possibilities by developing a battery of coordinated movement tests and examining motor deficits in dopamine ␤-hydroxylase knockout (Dbh؊/؊) mice that lack NE altogether. We detected no motor abnormalities in MPTP-treated control mice, despite an 80% loss of striatal dopamine (DA) terminals. Dbh؊/؊ mice, on the other hand, were impaired in most tests and also displayed spontaneous dyskinesias, despite their normal striatal DA content. A subset of these impairments was recapitulated in control mice with 80% NE lesions and reversed in Dbh؊/؊ mice, either by restoration of NE or treatment with a DA agonist. MPTP did not exacerbate baseline motor deficits in Dbh؊/؊ mice. Finally, striatal levels of phospho-ERK-1/2 and ⌬FosB/FosB, proteins which are associated with PD and dyskinesias, were elevated in Dbh؊/؊ mice. These results suggest that loss of locus coeruleus neurons contributes to motor dysfunction in PD.dopamine ͉ Parkinson's disease ͉ dyskinesias ͉ dopamine ␤-hydroxylase P arkinson's disease (PD) affects Ϸ1% of the world's aging population (1). Despite this high prevalence and intensive research into its origins, the etiology of PD remains largely unknown. The disease is characterized by degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SN), and symptoms, which tend to manifest when Ϸ80% of striatal DA is lost, include bradykinesia, postural instability, rigidity, and resting tremor. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin, is known to produce parkinsonism in humans and causes severe DA loss in animals (2). Because of its ability to recapitulate the neuropathology of PD, MPTP is used widely in PD research. However, MPTP has been unable to reliably reproduce the motor symptoms of PD in mice, which limits the utility of MPTP-treated mice as an animal model of the disease (3). Differences in mouse strain and experimental paradigms may at least partially account for these inconsistencies.Despite the focus on DA, PD is more accurately described as a multisystem disorder that features a profound albeit underappreciated loss of locus coeruleus (LC) neurons, as well as variable damage to other brain regions (4-6). Postmortem studies indicate that neuronal degeneration in the LC is comparable to that in the substantia nigra pars compacta, and that it may a...

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Reduced MPTP toxicity in noradrenaline transporter knockout mice

Cited by 74 publications

References 60 publications

Ameliorating Effect of Dimethylsulfoniopropionate on the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson's Disease of Mice

Ameliorating Effect of Dimethylsulfoniopropionate on the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson's Disease of Mice

Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease

Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice

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