Full text vitexin protects dopaminergic neurons in mptp. The neuroprotective effects of cinnamic aldehyde in an. This chapter provides a detailed discussion on the mptp 1methyl4phenyl1,2,3,6tetrahydropyridine mouse model of parkinsons disease pd. Abstractthis protocol describes our method of producing a reliable mouse model of parkinson s disease pd using the neurotoxin 1.
Parkinson disease pd is the third most common neurodegenerative disorder affecting humans. Behavioral assessments of spontaneous locomotion in a murine. Neuroprotective effects of salidroside in the mptp mouse model of parkinsons disease. Parkinsons disease pd is a chronic neurodegenerative disorder affecting over four million people worldwide dorsey et al. Parkinsons disease pd is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and dementia. Since a range of immunotherapies have recently been proposed as a therapeutic strategy for parkinsons disease pd, we investigated the effects of an ivig treatment in a neurotoxininduced animal model of pd. Physical exercise modulates ldoparegulated molecular pathways in the mptp mouse model of parkinsonsdisease cornelius j. Researcharticle neuroprotective effects of salidroside in the mptp mouse model of parkinsons disease. Parkinsons disease pd is a progressive neurodegenerative disease which is characterized by the degeneration of dopaminergic neurons in. Mptp was first discovered by a chemistry student in 1976, who was trying to synthesize a synthetic heroin, but instead. Among the most widely used models of parkinson s disease pd are those that employ toxins, especially 1methyl4phenyl1,2,3,6tetrahydropyridine mptp.
To determine whether ld formation occurs in mammalian models and participates in the pathogenesis of pd, we generated the mptp neurotoxininduced pd mouse model for chronic mitochondrial dysfunctionassociated loss of da neurons using a previously described protocol lu et al. Faull, the use of cfos as a metabolic marker in neuronal pathway tracing, journal of neuroscience methods, vol. Impact of intravenous immunoglobulin on the dopaminergic. Induction of adaptive immunity leads to nigrostriatal disease. It is known that under conditions of oxidative stress, the transcription factor nfe2related factor nrf2 binds to antioxidant response element are to induce antioxidant and. However, the details regarding the causes of the disease and its course are much less clear. Parkinsons disease pd is an ageassociated neurodegenerative disorder hallmarked by a loss of mesencephalic dopaminergic neurons. A novel biomechanical analysis of gait changes in the mptp.
Protection of vibration training on dopamine neurons and. Understanding cognitive deficits in parkinsons disease. Oxidative stress has been implicated in the etiology of parkinson s disease pd and in the 1methyl4phenyl1,2,3,6tetrahydropyridine mptp animal model of pd. Both systemic and intracranial applications of mptp produce severe loss of dopaminergic neurons projecting to the striatum. Mptp induces alphasynuclein aggregation in the substantia nigra of baboons. Jan 01, 2011 among the most widely used models of parkinsons disease pd are those that employ toxins, especially 1methyl4phenyl1,2,3,6tetrahydropyridine mptp.
Protocol for the mptp mouse model of parkinsons disease. Our aim was to determine if pramipexole, a d3 preferring agonist, effectively reduced dopamine neuron and fiber loss in the 1methyl4phenyl1,2,3,6tetrahydropyridine mptp mouse model when given at intraperitoneal doses corresponding to clinical doses. Schwarzschild1 1molecular neurobiology laboratory, department of neurology, massachusetts general hospital. Author information1department of neurology, columbia university, new york, ny 10032, usa. A guide to neurotoxic animal models of parkinsons disease. Stress in an experimental model of parkinsons disease. Pdf protocol for the mptp mouse model of parkinsons disease. To assess the validity of the mptp mouse model for pd pathogenesis, we.
In this study, we used a videobased analysis system to develop and validate a novel protocol for tracking locomotor performance in the 1methyl4phenyl1,2,3,6tetrahydropyridine mptp mouse model of pd. Experimental model of parkinsons disease inflammation and. Mice and nonhuman primates systemically injected with mptp, a mitochondrial neurotoxin, show loss of mesencephalic dopaminergic neurons with concomitant loss of striatal da content. Parkinsons disease pd is a progressive neurodegenerative disorder characterized by the preferential loss of dopaminergic neurons in the snpc, affecting 23% of the population over the age of 65 poewe et al. Mice treated with the neurotoxin 1methyl4phenyl1,2,3,6tetrahydropyrimidine mptp are widely used as a model for pd.
Aberrant tonic inhibition of dopaminergic neuronal activity. Despite numerous efforts to develop progressive toxic protocols in mice, few fully reflect the hallmarks of the disease. Mptp exposure in mice leads to a variety of symptoms reproducing those observed in human parkinsons disease including akinesia, rigidity, tremor, gait, and postural disturbances. Among the most widely used models of parkinsons disease pd are those that employ toxins, especially. Petzer,2 roland staal,3 yuehang xu,1 mark beilstein,1 patricia k. While mptp itself has no psychoactive effects, the compound may be accidentally produced during the manufacture. Accurate recapitulation of the pd movement phenotype in animal models of the disease is critical for understanding disease etiology and developing novel therapeutic treatments. It is classically characterized by the emergence of motor symptoms such as rigidity, tremor, postural unbalance, and bradykinesiaakinesia braak et al. Among the most widely used models of parkinsons disease pd are those that employ toxins, especially 1methyl4phenyl1,2,3,6tetrahydropyridine mptp.
Immunohistochemical analysis was performed on mptpchallenged mice treated with standard bvpla 2 purified from crude bv 0. Altogether, these findings highlight the suitability of the mptp macaque model of pd as a tool to model the sleepwake disturbances of the human disease. Among the most widely used models of parkinsons disease pd are those that employ toxins, especially 1methyl 4phenyl1,2,3,6tetrahydropyridine mptp. The neuroprotective effect of dimethyl fumarate in an mptp. Noninvasive ultrasound deep brain stimulation for the. It has been used to study disease models in various animal studies. This protocol describes our method of producing a reliable mouse model of parkinsons disease pd using the neurotoxin 1methyl4phenyl1,2,3,6tetrahydropyridine mptp. Sonsalla,3 kay castagnoli,2 neal castagnoli jr,2 and michael a.
Depending on the protocol used, mptp yields large variations in nigral cell loss, striatal dopamine loss and behavioral deficits. Dosedependent neuroprotective effect of standardized bee. Nonetheless, mptp mouse models mimic many aspects of the disease and are therefore important tools for understanding pd. Behavioral assessments of spontaneous locomotion in a. Recently, the neuroprotective effects of ca have been reported in various neurodegenerative disorders, including parkinsons disease pd. This protocol describes our method of producing a reliable mouse model of parkinson s disease pd using the neurotoxin 1methyl4phenyl1,2,3,6tetrahydropyridine mptp. A model of mptpinduced parkinsons disease in the goldfish. Ultimately, this may help in deciphering the specific role of neurotransmitter depletion in the occurrence of these symptoms. Depending on the protocol used, mptp yields large variations in nigral cell loss, striatal dop.
Mice received four injections of mptp 15 mgkg at 2. Pet imaging a mptpinduced mouse model of parkinsons. Induced models of parkinsons disease in mice and non. Abstract parkinsons disease pd is characterized by dopaminergic da neuron death in the substantia nigra sn and subsequent striatal adaptations. The neurotoxin mptp was employed to create a subacute parkinsons disease pdlike model in c57bl6 mice. Nrf2mediated neuroprotection in the mptp mouse model of parkinsons disease. Protection of vibration training on dopamine neurons and upregulation of brainderived neurotrophic factor in a mptp mouse model of parkinsons disease zhao li1, he ling xiao1, huang su na2, gong lijing1, li lan2, lv yuanyuan1, zhong ming qian2 1 department of sports physiology, beijing sport university, beijing 84, china. In the pole test, mptp treatment signi cantly extended the time of tturn to 3. Neuroprotection by caffeine and a 2a adenosine receptor inactivation in a model of parkinsons disease jiangfan chen,1 kui xu,1 jacobus p. Although it is clear that the etiology of a small number of pd cases is strictly genetic either. Effects of egcg on mptpinduced motor deficits in an accelerated rotarod test a and on oxidative stress assessed as serum protein carbonyl concentration b in a mouse model of parkinson disease. Pdf this protocol describes our method of producing a reliable mouse model of parkinsons disease pd using the neurotoxin. Institutes of health guidelines and were approved by the institutional animal care and.
Oct 11, 2004 our aim was to determine if pramipexole, a d3 preferring agonist, effectively reduced dopamine neuron and fiber loss in the 1methyl4phenyl1,2,3,6tetrahydropyridine mptp mouse model when given at intraperitoneal doses corresponding to clinical doses. It is known that under conditions of oxidative stress, the transcription factor nfe2related factor nrf2 binds to antioxidant response element are to induce antioxidant and phase ii detoxification enzymes. This unit describes protocols for the production of stable and substantial lesions in the dopaminergic nigrostriatal pathway of mice and non. This chapter provides a detailed discussion on the mptp 1methyl4phenyl1,2,3,6tetrahydropyridine mouse model of parkinson s disease pd. Critical role for the astrocyte peichun chena, marcelo r. We discuss the particulars of the model, provide key references and outline what investigators need to know to develop the mptp mouse model of pd safely and successfully. Cinnamic aldehyde ca, a key flavor compound in cinnamon essential oil, has been identified as an antioxidant, antiangiogenic, and antiinflammatory material. Immunohistochemical analysis was performed on mptp challenged mice treated with standard bvpla 2 purified from crude bv 0. Mice with mptp treatment are used as a model that is easy to handle, affordable, and highly reproducible by establishing a chronic mptp protocol 8. Structurally, the toxin, mptp, resembles a number of known environmental compounds, including herbicides such as paraquat and the garden insecticidefish toxin, rotenone. In vivo models of parkinsons diseasea model similarities to human disease differences from human disease comments in vivo neurotoxin models mptp primates parkinsonism acute or subacute process rodents are less. Epigallocatechin gallate has a neurorescue effect in a mouse.
Intravenous immunoglobulin ivig is a bloodderived product, used for the treatment of immunodeficiency and autoimmune diseases. The protective effect of sal against pdrelated behavioral disorders was evaluated by pole test and open field test in the mptp induced pd mouse model. Parkinsons disease pd is a chronic and progressive. Chronic and progressive parkinsons disease mptp model in adult. Dynamic changes in the nigrostriatal pathway in the mptp. For many researchers, however, the mouse remains a popular choice owing to a lack of resources and trained personnel for the monkey model. Department of neurology, columbia university, new york, ny, usa. Vertical grid test and modified horizontal grid test are sensitive methods for evaluating motor dysfunctions in the mptp mouse model of parkinsons disease. Low dose pramipexole is neuroprotective in the mptp mouse. Motor deficits do not fully replicate those seen in pd. Oxidative stress has been implicated in the etiology of parkinsons disease pd and in the 1methyl4phenyl1,2,3,6tetrahydropyridine mptp animal model of pd. Nov 15, 2007 parkinson s disease pd has been modeled in humans, lower primates, and to a lesser extent in some other vertebrates by the administration of the potent neurotoxin 1methyl4phenyl1,2,3,6. We applied a quantitative noninvasive pet imaging technique to follow this degeneration process in an mptpinduced mouse model of pd.
Micewerepermittedtoadapttothe experimental environment for 2. We also determined whether subchronic treatment with pramipexole regulates dopamine transporter function, thereby reducing intracellular. Parkinsons disease pd is characterized by the loss of dopamineproducing neurons in the nigrostriatal system. Epigallocatechin gallate has a neurorescue effect in a. Involvement of the pi3kaktgsk3pathway weizhang,1 honghe,1 hujiesong,2 junjiezhao,1 taoli,1 leitaowu,1.
However, most existing behavioral assays currently applied to such animal. Parkinson disease pd is a chronic neurodegenerative disorder characterized primarily by the progressive degeneration of dopaminergic neurons in the substantia nigra sn, resulting in irreversible motor dysfunction such as resting tremor, bradykinesia, and postural instability. Europe pmc is an archive of life sciences journal literature. Przedborski, protocol for the mptp mouse model of parkinsons disease, nature protocols, vol.
In this chapter we consider whether mice treated with mptp 1methyl4phenyl1,2,3,6tetrahydropyridine represent a suitable model for parkinsons disease pd. We also determined whether subchronic treatment with pramipexole regulates dopamine transporter function, thereby reducing. Przedborski, protocol for the mptp mouse model of parkinsons disease. Johnsona,c,e,f,2 aschool of pharmacy, cmolecular and environmental toxicology center, ewaisman center, and fcenter of neuroscience, university of. Parkinsons disease pd has been modeled in humans, lower primates, and to a lesser extent in some other vertebrates by the administration of the potent neurotoxin 1. In neurons, autophagy is tightly regulated, and consequently, the dysregulation of autophagy. Vitexin protects dopaminergic neurons in mptpinduced parkinsons disease through pi3kakt signaling pathway ming hu, fangming li, weidong wang department of neurology, shenzhen hospital, southern medical university, shenzhen, guangdong, china abstract. Validity of the mptptreated mouse as a model for parkinson. Physical exercise modulates ldoparegulated molecular. Protective effect of chinonin in mptpinduced c57bl6 mouse. Animal models have significantly enriched our current understanding of the progression of this disease. Mptp is the only known dopaminergic neurotoxin capable of causing a clinical picture in both humans and monkeys that is indistinguishable from pd.
Validity of the mptptreated mouse as a model for parkinsons disease. The exact causes and mechanisms of pathogenesis of pd remain unknown. Neuroprotective effects of salidroside in the mptp mouse. Among various neurotoxinbased models of pd, 1methyl4phenyl1,2,3,6.
Protocol for the mptp mouse model of parkinson s disease. Research article neuroprotective effects of salidroside in. Chinonin 10, 20, 40 mgkg body weight was intraperitoneally administered 0. In the pole test, mptp treatment significantly extended the time of tturn to s and that of tla to s compared with the control group figures 1a and 1b. Nrf2mediated neuroprotection in the mptp mouse model of. We classify the disease model system as one that is capable of reproducing certain aspects of the human disease ranging from pathology to clinical symptoms. The dopaminergic neural loss induced by our chronic mptp protocol. In this study, we show an upregulation of inducible nitric oxide synthase and a downregulation of neutral sphingomyelinase in the hippocampus of 1methyl4phenyl1,2,3,6tetrahydropyridine mptp induced mouse model of parkinsons disease. Dynamic changes in the nigrostriatal pathway in the mptp mouse. This protocol describes our method of producing a reliable mouse model of parkinsons disease pd using the neurotoxin 1methyl4 phenyl1,2,3,6tetrahydropyridine mptp. Dosedependent inhibitory effect of purified standard bvpla 2 on microglial activation in the mptp mouse model of pd.
579 1175 1090 1651 935 1626 1518 1007 815 1230 1183 1133 1249 1279 1375 1183 752 93 1281 628 134 1415 1322 370 1143 739 890 490 1370 526