Accurate recapitulation of the pd movement phenotype in animal models of the disease is critical for understanding disease etiology and developing novel therapeutic treatments. This chapter provides a detailed discussion on the mptp 1methyl4phenyl1,2,3,6tetrahydropyridine mouse model of parkinsons disease pd. The neuroprotective effects of cinnamic aldehyde in an. Among the most widely used models of parkinsons disease pd are those that employ toxins, especially 1methyl 4phenyl1,2,3,6tetrahydropyridine mptp. 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. Parkinsons disease pd is characterized by the loss of dopamineproducing neurons in the nigrostriatal system. Przedborski, protocol for the mptp mouse model of parkinsons disease. Structurally, the toxin, mptp, resembles a number of known environmental compounds, including herbicides such as paraquat and the garden insecticidefish toxin, rotenone. Protocol for the mptp mouse model of parkinson s disease.
This protocol describes our method of producing a reliable mouse model of parkinsons disease pd using the neurotoxin 1methyl4phenyl1,2,3,6tetrahydropyridine mptp. Neuroprotective effects of salidroside in the mptp mouse model of parkinsons disease. Behavioral assessments of spontaneous locomotion in a. Dosedependent inhibitory effect of purified standard bvpla 2 on microglial activation in the mptp mouse model of pd. 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. Europe pmc is an archive of life sciences journal literature. Parkinsons disease pd is a chronic and progressive. Protective effect of chinonin in mptpinduced c57bl6 mouse. Focus on history of freezing episodes, tremors, bradykinesia, rigidit y, falls during medication on or off times, dropping items, fine and gross motor coordination,difficulty swallowingtalking loud memory, hep, time schedule for meds. Protection of vibration training on dopamine neurons and. We also determined whether subchronic treatment with pramipexole regulates dopamine transporter function, thereby reducing intracellular. Institutes of health guidelines and were approved by the institutional animal care and.
Nonetheless, mptp mouse models mimic many aspects of the disease and are therefore important tools for understanding pd. Impact of intravenous immunoglobulin on the dopaminergic. Abstract parkinsons disease pd is characterized by dopaminergic da neuron death in the substantia nigra sn and subsequent striatal adaptations. Parkinsons disease pd is the second most common neurodegenerative. 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. Chinonin 10, 20, 40 mgkg body weight was intraperitoneally administered 0. Neuroprotective effects of salidroside in the mptp mouse. Schwarzschild1 1molecular neurobiology laboratory, department of neurology, massachusetts general hospital. Neuroprotection by caffeine and a adenosine receptor. 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.
Among various neurotoxinbased models of pd, 1methyl4phenyl1,2,3,6. This protocol describes our method of producing a reliable mouse model of parkinsons disease pd using the neurotoxin 1methyl4 phenyl1,2,3,6tetrahydropyridine mptp. Understanding cognitive deficits in parkinsons disease. However, the details regarding the causes of the disease and its course are much less clear. For many researchers, however, the mouse remains a popular choice owing to a lack of resources and trained personnel for the monkey model. This unit describes protocols for the production of stable and substantial lesions in the dopaminergic nigrostriatal pathway of mice and non. The exact etiology and natural course of pd have yet to be fully clarified but involve dysfunction of numerous systemlevel processes, including mitochondrial. Oxidative stress has been implicated in the etiology of parkinsons disease pd and in the 1methyl4phenyl1,2,3,6tetrahydropyridine mptp animal model of pd. 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. 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.
Przedborski, protocol for the mptp mouse model of parkinsons disease, nature protocols, vol. Animal models have significantly enriched our current understanding of the progression of this disease. Experimental model of parkinsons disease inflammation and. While mptp itself has no psychoactive effects, the compound may be accidentally produced during the manufacture. Stress in an experimental model of parkinsons disease. Immunohistochemical analysis was performed on mptpchallenged mice treated with standard bvpla 2 purified from crude bv 0. The characteristic brain pathology and motor and nonmotor symptoms of parkinsons disease pd are well established. In neurons, autophagy is tightly regulated, and consequently, the dysregulation of autophagy. Mptp is the only known dopaminergic neurotoxin capable of causing a clinical picture in both humans and monkeys that is indistinguishable from pd. Parkinsons disease pd is an ageassociated neurodegenerative disorder hallmarked by a loss of mesencephalic dopaminergic neurons.
A guide to neurotoxic animal models of parkinsons disease. Both systemic and intracranial applications of mptp produce severe loss of dopaminergic neurons projecting to the striatum. Protocol for the mptp mouse model of parkinsons disease. Researcharticle neuroprotective effects of salidroside in the mptp mouse model of parkinsons disease. Epigallocatechin gallate has a neurorescue effect in a. Parkinson disease pd is the third most common neurodegenerative disorder affecting humans. Epigallocatechin gallate has a neurorescue effect in a mouse. 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. 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. Faull, the use of cfos as a metabolic marker in neuronal pathway tracing, journal of neuroscience methods, vol. Numerous researchers in the past have attempted to track the progression of dopaminergic depletion in pd. The dopaminergic neural loss induced by our chronic mptp protocol. 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.
However, most existing behavioral assays currently applied to such animal. Author information1department of neurology, columbia university, new york, ny 10032, usa. Full text vitexin protects dopaminergic neurons in mptp. It is classically characterized by the emergence of motor symptoms such as rigidity, tremor, postural unbalance, and bradykinesiaakinesia braak et al. This chapter provides a detailed discussion on the mptp 1methyl4phenyl1,2,3,6tetrahydropyridine mouse model of parkinson s disease pd. Pdf protocol for the mptp mouse model of parkinsons disease. Vertical grid test and modified horizontal grid test are sensitive methods for evaluating motor dysfunctions in the mptp mouse model of parkinsons disease. 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.
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. Among the most widely used models of parkinsons disease pd are those that employ toxins, especially. Physical exercise modulates ldoparegulated molecular pathways in the mptp mouse model of parkinsonsdisease cornelius j. Sonsalla,3 kay castagnoli,2 neal castagnoli jr,2 and michael a. Behavioral assessments of spontaneous locomotion in a murine. Mptp was first discovered by a chemistry student in 1976, who was trying to synthesize a synthetic heroin, but instead. Pdf this protocol describes our method of producing a reliable mouse model of parkinsons disease pd using the neurotoxin. We also determined whether subchronic treatment with pramipexole regulates dopamine transporter function, thereby reducing. In this chapter we consider whether mice treated with mptp 1methyl4phenyl1,2,3,6tetrahydropyridine represent a suitable model for parkinsons disease pd. 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. Physical exercise modulates ldoparegulated molecular. Among the most widely used models of parkinson s disease pd are those that employ toxins, especially 1methyl4phenyl1,2,3,6tetrahydropyridine mptp. A novel biomechanical analysis of gait changes in the mptp.
Parkinsons disease pd is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and dementia. Induction of adaptive immunity leads to nigrostriatal disease. 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. A model of mptpinduced parkinsons disease in the goldfish. Although it is clear that the etiology of a small number of pd cases is strictly genetic either. Johnsona,c,e,f,2 aschool of pharmacy, cmolecular and environmental toxicology center, ewaisman center, and fcenter of neuroscience, university of. Validity of the mptptreated mouse as a model for parkinson.
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. Dynamic changes in the nigrostriatal pathway in the mptp mouse. Chronic and progressive parkinsons disease mptp model in adult. 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. Frontiers plin4dependent lipid droplets hamper neuronal. 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. Immunohistochemical analysis was performed on mptp challenged mice treated with standard bvpla 2 purified from crude bv 0.
Mice received four injections of mptp 15 mgkg at 2. Parkinsons disease pd is a chronic neurodegenerative disorder affecting over four million people worldwide dorsey et al. Motor deficits do not fully replicate those seen in pd. Cinnamic aldehyde ca, a key flavor compound in cinnamon essential oil, has been identified as an antioxidant, antiangiogenic, and antiinflammatory material. Jan 01, 2011 among the most widely used models of parkinsons disease pd are those that employ toxins, especially 1methyl4phenyl1,2,3,6tetrahydropyridine mptp.
Mptp induces alphasynuclein aggregation in the substantia nigra of baboons. 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. Despite numerous efforts to develop progressive toxic protocols in mice, few fully reflect the hallmarks of the disease. Department of neurology, columbia university, new york, ny, usa. It has been used to study disease models in various animal studies. Mice and nonhuman primates systemically injected with mptp, a mitochondrial neurotoxin, show loss of mesencephalic dopaminergic neurons with concomitant loss of striatal da content. Noninvasive ultrasound deep brain stimulation for the. We applied a quantitative noninvasive pet imaging technique to follow this degeneration process in an mptpinduced mouse model of pd. Petzer,2 roland staal,3 yuehang xu,1 mark beilstein,1 patricia k. Involvement of the pi3kaktgsk3pathway weizhang,1 honghe,1 hujiesong,2 junjiezhao,1 taoli,1 leitaowu,1.
Intravenous immunoglobulin ivig is a bloodderived product, used for the treatment of immunodeficiency and autoimmune diseases. Abstractthis protocol describes our method of producing a reliable mouse model of parkinson s disease pd using the neurotoxin 1. 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. To assess the validity of the mptp mouse model for pd pathogenesis, we. 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. The exact causes and mechanisms of pathogenesis of pd remain unknown. Ultimately, this may help in deciphering the specific role of neurotransmitter depletion in the occurrence of these symptoms. The neurotoxin mptp was employed to create a subacute parkinsons disease pdlike model in c57bl6 mice. Mice treated with the neurotoxin 1methyl4phenyl1,2,3,6tetrahydropyrimidine mptp are widely used as a model for pd. 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. Neuroprotection by caffeine and a 2a adenosine receptor inactivation in a model of parkinsons disease jiangfan chen,1 kui xu,1 jacobus p. Abstract despite the different animal models of parkinsons disease developed.
Validity of the mptptreated mouse as a model for parkinsons disease. Among the most widely used models of parkinsons disease pd are those that employ toxins, especially 1methyl4phenyl1,2,3,6tetrahydropyridine mptp. 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. Aberrant tonic inhibition of dopaminergic neuronal activity. Pet imaging a mptpinduced mouse model of parkinsons. This protocol describes our method of producing a reliable mouse model of parkinson s disease pd using the neurotoxin 1methyl4phenyl1,2,3,6tetrahydropyridine mptp. In the pole test, mptp treatment signi cantly extended the time of tturn to 3. Critical role for the astrocyte peichun chena, marcelo r. Micewerepermittedtoadapttothe experimental environment for 2. Recently, the neuroprotective effects of ca have been reported in various neurodegenerative disorders, including parkinsons disease pd.
Low dose pramipexole is neuroprotective in the mptp mouse. Parkinsons disease pd is a progressive neurodegenerative disease which is characterized by the degeneration of dopaminergic neurons in. Nrf2mediated neuroprotection in the mptp mouse model of parkinsons disease. Induced models of parkinsons disease in mice and non. Dynamic changes in the nigrostriatal pathway in the mptp. Dosedependent neuroprotective effect of standardized bee. Depending on the protocol used, mptp yields large variations in nigral cell loss, striatal dopamine loss and behavioral deficits. 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. Depending on the protocol used, mptp yields large variations in nigral cell loss, striatal dop. Research article neuroprotective effects of salidroside in. The neuroprotective effect of dimethyl fumarate in an mptp.
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