MPTP treatment in mice does not transmit and cause Parkinsonian neurotoxicity in non-treated cagemates through close contact

Lau, Yuen-Sum; Novikova, Lesya; Roels, Christina

doi:10.1016/j.neures.2005.04.010

Cited by 26 publications

(16 citation statements)

References 18 publications

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“…Mice were fed normal (0.8%) or high (1.6%) NaCl diet ad libitum for one week, respectively. Urine, collected in metabolic cages one day prior to euthanasia, was analyzed for concentrations of dopamine by high performance liquid chromatography (HPLC) with electrochemical detection (15) or enzyme-linked immunosorbent assay (ELISA) (Genway, San Diego, CA). Kidneys, hearts and brains were harvested from pentobarbital anesthetized mice for immunoblotting (16-19) and reverse transcript polymerase chain reaction (RT-PCR) (20).…”

Section: Methodsmentioning

confidence: 99%

Upregulation of Renal D ₅ Dopamine Receptor Ameliorates the Hypertension in D ₃ Dopamine Receptor–Deficient Mice

et al. 2013

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D3 dopamine receptor (D3R) deficient mice have renin-dependent hypertension associated with sodium retention but the hypertension is mild. In order to determine if any compensatory mechanisms in the kidney are involved in the regulation of blood pressure with disruption of Drd3, we measured the renal protein expression of all dopamine receptor subtypes (D1R, D2R, D4R, and D5R) in D3R homozygous (D3−/−) and heterozygous (D3+/−) knockout mice and their wild-type (D3+/+) littermates. The renal immunohistochemistry and protein expression of D5R was increased (n=5/group) in D3−/−mice, renal D4R protein expression was decreased, while renal protein expressions of D1R and D2R were similar in both groups. Renal D5R protein expression was also increased in D3+/− (n=5/group) relative to D3+/+ mice, while D1R, D2R, and D4R protein expressions were similar in D3+/− and D3+/+ mice. The increase in renal D5R protein expression was abolished when D3−/− mice were fed a high salt diet. Treatment with the D1-like receptor antagonist, SCH23390, increased the blood pressure in anesthetized D3−/− but not D3+/+ mice (n=4/group), suggesting that the renal upregulation of D5R may have minimized the hypertension in D3−/− mice. The renal D5R protein upregulation was not due to increased transcription because renal mRNA expression of D5R was similar in D3−/− and D3+/+ mice. Our findings suggest that the renal upregulation of D5R may have minimized the hypertension that developed in D3−/− mice.

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Section: Methodsmentioning

confidence: 99%

Upregulation of Renal D ₅ Dopamine Receptor Ameliorates the Hypertension in D ₃ Dopamine Receptor–Deficient Mice

et al. 2013

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“…Experiments were conducted 6 weeks post-chronic treatment. Safety precautions for the use of MPTP during chemical preparation and animal injections were taken according to the procedures previously described (Lau et al, 2005). Control mice were treated with probenecid only.…”

Section: Methodsmentioning

confidence: 99%

“…Control mice were treated with probenecid only. Probenecid was used to inhibit the rapid clearance and excretion of MPTP and its metabolites from the brain and kidney, and it alone did not produce any significant neurotoxic effect; but in combination it potentiated the neurotoxicity of MPTP (Lau, 2005; Lau et al, 2005; Barber-Singh et al, 2009). For comparison, we also included a group of acute MPTP-treated young mice, which were injected with two doses of MPTP hydrochloride (25 mg/kg/injection in saline, s.c.) 2 h apart.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson’s disease

Patki

Che

Lau

2009

Front. Ag. Neurosci.

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Mitochondrial oxidative stress and dysfunction has been implicated as a possible mechanism for the onset and progression of Parkinson-like neurodegeneration. However, long-term mitochondrial defects in chronic animal neurodegenerative models have not been demonstrated. In this study, we investigated the function of striatal mitochondria 6 weeks after the induction of a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (MPD). Although severe depression of mitochondrial respiration was observed immediately after acute administrations of MPTP, we failed to detect a significant mitochondrial inhibition in presence of striatal dopamine (DA) deficit 6 weeks after the chronic MPD induction in young adult mice. In contrast, when aged mice were chronically treated with MPTP and at 6 weeks post-treatment, these animals suffered an inhibition of the basal (state 4) and adenosine 5′-diphosphate-stimulated (state 3) respiration and a fall in adenosine triphosphate level in the striatal mitochondria. The aged chronic MPD also brought about a sustained diminution of striatal anti-oxidant enzyme levels including that of superoxide dismutases and cytochrome c. The mitochondrial deficits in the striatum of aged chronic MPD 6 weeks after treatment were further correlated with significant losses of striatal DA, tyrosine hydroxylase, DA uptake transporter, and with impaired movement when tested on a challenging beam. Our findings suggest that MPTP may trigger the neurodegenerative process by obstructing the mitochondrial function; however, striatal mitochondria in young animals may potentially rejuvenate, whereas mitochondrial dysfunction is sustained in the aged chronic MPD. Therefore, the aged chronic MPD may serve as a suitable investigative model for further elucidating the integral relationship between mitochondrial dysfunction and neurodegenerative disorder, and for assessing the therapeutic efficacy of mitochondrial protective agents as potential neuroprotective drugs.

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“…Groups II and III received MPTP injection (30 mg/kg; i.p) starting from 4th to 7th day of the experimental period. Guidelines for handling MPTP were strictly followed as described previously [15]. Groups III and IV received CNB-001 (24 mg/kg, i.p, 1 h prior to MPTP injection) for 7 consecutive days.…”

Section: Methodsmentioning

confidence: 99%

CNB-001 a Novel Curcumin Derivative, Guards Dopamine Neurons in MPTP Model of Parkinson’s Disease

Jayaraj

Elangovan

Krishnan

et al. 2014

BioMed Research International

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Copious experimental and postmortem studies have shown that oxidative stress mediated degeneration of nigrostriatal dopaminergic neurons underlies Parkinson's disease (PD) pathology. CNB-001, a novel pyrazole derivative of curcumin, has recently been reported to possess various neuroprotective properties. This study was designed to investigate the neuroprotective mechanism of CNB-001 in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent model of PD. Administration of MPTP (30 mg/kg for four consecutive days) exacerbated oxidative stress and motor impairment and reduced tyrosine hydroxylase (TH), dopamine transporter, and vesicular monoamine transporter 2 (VMAT2) expressions. Moreover, MPTP induced ultrastructural changes such as distorted cristae and mitochondrial enlargement in substantia nigra and striatum region. Pretreatment with CNB-001 (24 mg/kg) not only ameliorated behavioral anomalies but also synergistically enhanced monoamine transporter expressions and cosseted mitochondria by virtue of its antioxidant action. These findings support the neuroprotective property of CNB-001 which may have strong therapeutic potential for treatment of PD.

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MPTP treatment in mice does not transmit and cause Parkinsonian neurotoxicity in non-treated cagemates through close contact

Cited by 26 publications

References 18 publications

Upregulation of Renal D ₅ Dopamine Receptor Ameliorates the Hypertension in D ₃ Dopamine Receptor–Deficient Mice

Upregulation of Renal D ₅ Dopamine Receptor Ameliorates the Hypertension in D ₃ Dopamine Receptor–Deficient Mice

Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson’s disease

CNB-001 a Novel Curcumin Derivative, Guards Dopamine Neurons in MPTP Model of Parkinson’s Disease

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MPTP treatment in mice does not transmit and cause Parkinsonian neurotoxicity in non-treated cagemates through close contact

Cited by 26 publications

References 18 publications

Upregulation of Renal D 5 Dopamine Receptor Ameliorates the Hypertension in D 3 Dopamine Receptor–Deficient Mice

Upregulation of Renal D 5 Dopamine Receptor Ameliorates the Hypertension in D 3 Dopamine Receptor–Deficient Mice

Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson’s disease

CNB-001 a Novel Curcumin Derivative, Guards Dopamine Neurons in MPTP Model of Parkinson’s Disease

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Upregulation of Renal D ₅ Dopamine Receptor Ameliorates the Hypertension in D ₃ Dopamine Receptor–Deficient Mice

Upregulation of Renal D ₅ Dopamine Receptor Ameliorates the Hypertension in D ₃ Dopamine Receptor–Deficient Mice