Clinical Syndromes

Myoclonus Classification

The context in which myoclonus occurs aids diagnosis and helps organize the otherwise unruly heterogeneity of etiologies associated with myoclonus (Pranzatelli, 2003). It is routine to designate dyskinesia-plus syndromes in the etiologic classification of other movement disorders, and myoclonus is amenable to the same approach (Figure 1). FIGURE 1 Myoclonus-plus syndromes describe the relation of myoclonus to epilepsy and other movement disorders. Abbreviations ADCME, autosomal dominant...

Evaluation Of Dyskinesia In The

Although L-dopa is still the most effective treatment for PD, its ability to provide symptomatic relief is compromised by a development of motor fluctuations and dyskinesia in the majority of the patients (Obeso et al. 2000). Novel treatments for PD will be successful to the extent that they can either retard or prevent the development of these complications. Chase and collaborators described and successfully implemented a rat model of L-dopa-induced wearing-off fluctuations and dose failure...

Conclusions

Although the cause of most cases of PD remains unknown, the recently discovered familial forms of the disease have created a new approach for studying PD. Researchers continue to generate mice engineered with genetic mutations similar to those found in familial PD for assessing the long-term effects of these mutations in vivo. Researchers must characterize the behavior of these mice to validate their role as a model of PD and to determine optimal therapeutic targets. We gratefully acknowledge...

Tourette Syndrome

SINGER, CONSTANCE SMITH-HICKS, and DAVID LIEBERMAN Establishing an animal model that mimics the Gilles de la Tourette syndrome is a major challenge to investigators of movement disorders wishing to decipher the mechanisms of this uniquely human disease. Tourette syndrome (TS) is a common, inherited neuropsychiatric disorder, characterized by the presence of chronic involuntary motor and vocal tics that wax and wane. In addition to tics, individuals with this syndrome often have a...

Parkinson Disease And Motor Response Complications

Parkinson Disease and Levodopa Therapy PD is a neurodegenerative disorder of unknown etiology that currently afflicts over one million Americans. The pathological hallmark of PD is a selective loss of dopamin-ergic neurons in the substantia nigra pars compacta in the midbrain that projects to the corpus striatum (Greenfield and Bonsaquet 1953). When the loss of dopamine (DA) exceeds 50-80 , Parkinsonian symptoms become clinically evident (Ehringer and Hornykiewcz 1960 Hornykiewcz 1963). The...

Genetic Models Of Dystonia

Background The dystonia musculorum mutant emerged spontaneously at the Institute of Animal Genetics in Edinburgh and was first described in 1963 (Duchen et al. 1963). The mutation later proved allelic with the athetoid mutant (dtJ), which had arisen at least three times at the Jackson Laboratories in Bar Harbor, Maine (Duchen 1976). Several additional alleles have emerged independently in other mouse colonies, including one in Albany, New York (dtAlb) and another...

Historical Background

In the history of study of tremor, clinical analyses have also seemed to be ahead of experimental studies. Probably the most important study on tremor was that by James Parkinson, who wrote Essay on shaking palsy in 1817. Since then, the resting type of tremor has been widely recognized as Parkinsonian tremor. Since the discovery of nigral degeneration by Tretiakoff (1919) and later by Hassler (1938), and its relation to dopamine deficiency by Hornykiewicz (1963), understanding of Parkinson...

The Paraquat Model Of Parkinson Disease

Although PD is associated with pesticide exposure, no specific environmental toxin is linked directly to PD. Because of its structural similarity to MPP+, paraquat has generated substantial interest. Investigators studying a Taiwanese population determined a relationship between cumulative lifetime exposure to paraquat and development of PD (Liou et al. 1997). For these reasons, researchers have investigated the effects of paraquat on the central nervous system in model systems. The most...

Info

FIGURE 1 C. elegans strains containing integrated transgenes expressing polyglutamine-GFP fusions with and without TOR-2 or mutant TOR-2 (D368) protein. Suppression of protein aggregation is evident in the presence of wild-type torsin, whereas the mutant is incapable of this activity. FIGURE 1 C. elegans strains containing integrated transgenes expressing polyglutamine-GFP fusions with and without TOR-2 or mutant TOR-2 (D368) protein. Suppression of protein aggregation is evident in the...

Drosophila Models of Parkinson Disease

WHITWORTH Our knowledge of the molecular mechanisms of Parkinson disease (PD) has been dramatically advanced by the recent identification of genes underlying relatively rare heritable forms of this disorder (Hardy et al., 2003). These breakthroughs may provide a window into the mechanisms underlying the more common sporadic form of PD. However, our current understanding of the functions of these genes and the mechanisms by which their mutational alteration...

Pathological Features Of Parkinson Disease

Selective Nigrostriatal Dopaminergic Degeneration The cardinal feature of PD is relatively selective neurodegeneration of the nigrostriatal dopaminergic pathway, a neuronal circuit that controls motor activity. The symptoms of PD, including tremor, rigidity, and bradykinesia, are believed to result from depletion of striatal dopamine and the resultant changes in motor circuitry (Wooten 1997). For this reason, dopamine replacement therapy has been the gold standard for treating PD symptoms....

Tests Of Physiological Motor Behavior

Investigators have applied many tests with success for evaluating physiological motor performance in 6-OHDA-lesioned rats. Qualitative assessments of motor behavior in 6-OHDA-lesioned rats have revealed motor patterns that are reminiscent of Parkinsonian motor features in humans (Miklyaeva et al. 1995 Whishaw et al. 2002), including tremor (for review see Cenci et al. 2002). Although qualitative observations are extremely important for interpreting the significance of one's models, such...

Pathophysiological Findings In The Genetically Dystonic Hamster

In order to identify the underlying mechanism of the dystonic syndrome, the dtsz mutant has been extensively examined by neurochemical, immunohistological, and electrophysiological investigations (in comparison to nondystonic control hamsters). The paroxysmal nature of dyskinesias in dtsz hamsters provides the possibility for a separation of changes that are secondary to abnormal motor patterns (examinations in the absence versus in the presence of dystonic attacks). In addition, the...

Measuring Tremor During Sustained Forelimb Force In Unrestrained Rats

Initially, we developed the behavioral procedures and analytical methods presented in this section on forelimb tremor in an effort to quantify in rats the Parkinsonian-like side effects of the classical (typical), dopamine-receptor-blocking antipsychotic drugs (Fowler et al. 1990). The aim was to measure changes in response initiation, force control, and tremor in response to haloperidol treatment haloperidol is the prototypical high potency antipsychotic drug that frequently induces...

Clinical Features of Myoclonus

Myoclonus is a brief, jerklike contraction of a single muscle or muscle group that occurs as an isolated event or may occur in a repetitive regular or irregular manner. Myoclonus may be associated with dementias (e.g., Creutzfeldt-Jakob disease, subacute sclerosing panencephalitis, and Alzheimer disease), lipidoses (e.g., Tay-Sachs and Niemann-Pick diseases), leukodystrophies (e.g., Krabbe and Pelizaeus-Merzbacher diseases), cerebellar degenerations (e.g., Ramsay-Hunt syndrome), epilepsy...

The Rotenone Model Of Parkinson Disease

Mitochondrial Impairment in the Rotenone Model To model the systemic defect in complex I reported in PD, researchers have used rotenone exposure. Rotenone is a commonly used pesticide and potent, specific inhibitor of mitochondrial complex I. Although MPP+ is a mitochon-drial toxin, it is not well suited to mimic the systemic mito-chondrial impairment that occurs in PD. MPP+ is a substrate for the dopamine transporter and depends on expression of the dopamine transporter to gain access to...

Background

Tremor is the most common movement disorder affecting the world's population, with a prevalence of 1 to 2 (McAuley, 2001 Goetz, 2001). The clinical ramifications of tremor can often be debilitating, rendering patients unable to write or even feed themselves (Goetz, 2001). Although tremor is often associated with neurological conditions, such as Parkinson disease, it is capable of manifesting itself in many other ways. Essential tremor, the most common of the tremor disorders, is a primary...

Epidemiology Of Parkinson Disease

Parkinson disease is the second most common neu-rodegenerative disorder, trailing only Alzheimer disease. In the general population, the prevalence of PD is approximately 100 in 100,000. However, PD is an age-related illness and in individuals age sixty-five or older its prevalence mushrooms to 1-2 . The average age of symptom onset is sixty to sixty-five, but approximately 10 of PD patients develop symptoms before age forty. Investigators have never identified a uniform etiology for PD and it...

Pharmacotherapy Of Motor Response Complications In Mptp Nonhuman Primates

MPTP primate research on pharmacological interventions for PD have focused on practical approaches to restore the physiologic striatal dopaminergic transmission, as well as pharmacological strategies to prevent or reverse secondary changes at downstream sites (Anderson et al. 1999), occurring as a result of their nonphysiologic dopaminergic stimulation. The enhanced striatal glutamatergic and intra-cellular signaling cascades and motor response complications, can be attenuated by drugs that...

Hemifacial Spasm

The three primary symptoms of hemifacial spasm are involuntary muscle spasms, synkinesis, and lateral spread Sibony and Evinger 1998 . The initial clinical signs of hemifacial spasm are spontaneous, unilateral spasms of the eyelid muscle that progress to the remaining ipsilateral facial muscles over a period of weeks to months. Synkinesis is an inappropriate, involuntary activation of multiple muscles that normally do not act together. For example, stimulating the supraorbital branch of the...

Elegans Parkinson Disease Models

The single most obvious advantage of modeling in C. elegans has to be its exquisite genetics. Investigators can conduct genetic manipulation, either by forward or reverse genetics, in an expedited manner due to the short generation time of three days and the flexible sexual or asexual reproduction schemes of the hermaphrodite Jorgensen and Mango 2002 . The large number of progeny gt 300 produced by each hermaphrodite in its lifetime is an added bonus. Long-standing research in the field has...

Diagnosis Of Essential Tremor

The diagnostic approach to patients with ET includes the following steps a history, a physical examination, and, in some instances, selected laboratory tests 77 . Because a gene for ET has not yet been identified, there is no diagnostic genetic test for ET. Moreover, the utility of such a test would be limited for a variety of reasons. First, it is unknown what proportion of ET cases have an important genetic contribution, but this proportion may be much lower than 50 13,22 . Second, in those...

Elegans Parkinson Disease Models Generated By Chemical Treatments

Investigators have applied chemical neurotoxin treatments to C. elegans as a rapid and facile means to model Parkinson disease. Among neurotoxins specifically targeting dopaminergic neurons, we have used 6-hydroxydopamine 6-OHDA Nass et al. 2002 . A key to visualizing dopamin-ergic neurons in this study was using GFP controlled by the C. elegans dopamine transporter dat-1 Nass et al. 2001 . Transgenic injection of this construct permits identification of all eight hermaphrodite neurons under...

Tremormediating Circuit

Taking into account both the experimental results on Holmes tremor in monkeys and observations in patients with Parkinson disease, we have proposed a hypothetical circuit mediating the tremor Ohye, 1987 signals arising from the tremulous muscle from the muscle spindles go to the spinal cord, cross to take the spinothalamic tract of the contralateral side, ascend directly to the thalamic ventralis inter-medius nucleus, go up to cortical area 3 a deep in the central sulcus, descend to the...

Ozone

Cerebellothalamic Tract

FIGURE 6 Optimal area hatched for MVMT lesions associated with Holmes tremor. Left, Coronal section right, sagittal section GC, central gray Th, thalamus TTC, central tegmental tract LM, medial lemniscus. FIGURE 6 Optimal area hatched for MVMT lesions associated with Holmes tremor. Left, Coronal section right, sagittal section GC, central gray Th, thalamus TTC, central tegmental tract LM, medial lemniscus. touching the mediodorsal edge of the substantia nigra Figure 6 . In order to verify that...

Treatment of Dystonia

High-dose anticholinergic therapy was found to be effective in ameliorating dystonia, particularly in younger patients. Other agents such as baclofen, benzodiazepines, carbamazepine, and tetrabenazine are reported to benefit some dystonic patients Adler and Kumar 2000 Jankovic and Orman 1988 . In addition, all childhood onset dystonia patients deserve a trial of levodopa. Intramuscular injection of botulinum toxin is the most effective treatment for focal dystonia, and may be used in a limited...

Imaging

CT scan abnormalities including cerebellar or brainstem atrophy have been reported in patients with a variety of clinical labels such as OPCA, MSA, idiopathic cerebellar ataxia and non-familial degenerative disease Huang and Plaitakis, 1984 Uematsu et al., 1987 Staal et al., 1990 Klockgether et al., 1990a Wessel et al., 1993 . All of these studies have been biased towards the OPCA type of MSA and in some of them familial and sporadic OPCA were lumped together Uematsu et al., 1987 Wessel et al.,...

The Force Plate Actometer As A Method To Measure Motor Behavior In Rats And Mice

Actometer Cage

Whereas the foregoing sections on forelimb tremor and lick-force-rhythm described methods and results aimed at high precision characterization of movements of specific body parts, this section describes our approach to quantifying motor behavior of the whole body. Contemporary suppliers of behavioral instrumentation provide a range of options for recording and quantifying whole body movements. Photobeam actometers and video tracking systems are especially popular for measuring locomotor...

Use Of The Harmaline Tremor Model As A Therapeutic Screening Tool

The physiology and neurochemical anatomy of the IO provide a rich milieu for the development of drugs to treat ET. However, the relevance of harmaline-induced tremor to ET has not been completely established. For a case in point, previous physiological studies of harmaline-induced tremor in primates did not employ metabolic mapping or accelerometry thereby limiting comparisons to human ET. Moreover, the effects of alcohol and mechanical loads on harmaline-induced tremor have not been evaluated...

Clinical Picture

In a series of one hundred cases of clinically probable MSA Wenning et al., 1994a Wenning and Quinn, 1997 , at the last evaluation, 97 of patients with MSA had autonomic failure, 91 had parkinsonism, 52 had cerebellar features and 61 had pyramidal features. Autonomic failure may be associated with either levodopa unresponsive parkinsonism in 80 of cases MSA-P subtype or with cerebellar ataxia in 20 of cases MSA-C subtype . There is commonly clinical and subclinical evidence of autonomic failure...

Laboratory Investigations

At present, it is unclear whether or not ancillary studies would improve the diagnostic accuracy of these disorders and, if so, which studies would have higher positive predictive value, be less invasive, and more economic. Thus far, studies evaluating the overall concentration of tau phos-phorylated and not phosphorylated in cerebrospinal fluid CSF have not been useful in appropriately differentiating these disorders. Electrooculographic recording may help distinguish PSP patients from CBD at...

Investigations

The clinical diagnosis of MSA rests largely on history and physical examination. Additional investigations are particularly helpful in excluding differential diagnoses however, they may also support a presumptive clinical diagnosis. MSA-P patients are usually misdiagnosed as PD early in their disease. Regular follow-up is therefore required to detect development of atypical features suggestive of MSA. Autonomic function tests are a mandatory part of the diagnostic process and clinical follow-up...

Morphological Pattern Of Vulnerability

External examination of the brain is usually normal in MSA. However, when there is a significant involvement of the olivopontocerebellar system the appearances are characteristic. The cerebellum is small, with the hemispheres far from covering the occipital poles. The white matter of the cerebellum appears grey and the folia atrophic. The basis pontis and middle cerebellar peduncles are reduced. In the medulla, the protuberance of the inferior olives may be reduced. Occasionally, macroscopic...

Pathophysiology And Pathology

The pathophysiology of ET is poorly understood, but several lines of evidence suggest that this disease is probably neurodegenerative. As noted above, ET is clinically progressive. In addition, the gradual development of mild incoordination and mild ataxia in some longstanding cases supports the notion that the underlying pathological process is not static, but that it becomes more pervasive, eventually extending into brain systems that produce symptoms other than tremor. Also, clinicians have...

The Neuroanatomy And Function Of Dopamine Neurons In Drosophila

An extremely important feature of Drosophila that makes it useful for studying mechanisms of PD is its well-characterized and relatively simple dopamine neuron system. All of the Drosophila dopamine-producing neurons have been identified, and their development has been traced throughout the fly life cycle of this organism. Thus, investigators can readily identify genetic perturbations affecting the number, morphology, or locations of dopamine neurons in Drosophila. During embryonic and larval...

Activitydependent Neuronal Growth

IN HYPEREXCITABLE K CHANNEL MUTANTS A number of studies demonstrate that neuronal spikes and synaptic activity regulate the final projection pattern of terminal arbors Hubel et al., 1977 Harris, 1981 Meyer, 1982 Cline and Constantine-Paton, 1989 . In Drosophila, activity-dependent neuronal growth has been well-demonstrated in several hyperexcitable K channel mutants Table 1 . In addition to the striking electrophysiological defects Figures 4A and 7 , the number of synaptic boutons and terminal...

Neurobiology Of Tourette Syndrome

Neurobiology Tourette Syndrome

Despite a preponderance of evidence suggesting an organic rather than psychogenic origin for Tourette syndrome, the precise neurobiological abnormality remains speculative. Neuroanatomically, there is increasing evidence confirming that cortico-striato-thalamo-cortical CSTC pathways represent the site of origin not only for tics but also for accompanying neuropsychiatric problems. Pathophysiolog-ical hypotheses are generally based on either A, excess thalamic excitation or impaired...

Behavioral Analysis

The expected behavioral phenotype of a mouse model for movement disorders is initially determined in reference to the symptoms seen in patients. When a researcher sees a phe-notype resembling patient symptoms by simply observing the animals, concerns about the potential relevance of this model to the human disease are mostly eliminated. However, when the disorder is less severe, or more quantitative analysis is desired, the researcher can perform a battery of motor behavioral tests to reveal...

Neuropathologic Findings

Tufted Astrocyte

Investigators have published and validated consensus criteria for the pathologic diagnosis of PSP and CBD 5,10, 64 . Macroscopically, midbrain and pontine tegmentum atrophy and pallor of the substantia nigra are the most relevant findings in PSP, whereas CBD is characterized by asymmetric parietofrontal or frontotemporal cortical atrophy. figure 2 Morphological markers in CBD astrocytic plaque and PSP tufted astrocyte . Courtesy of Dr. Ian McKenzie. figure 2 Morphological markers in CBD...

Gene Targeting Method

Gene targeting relies on homologous recombination whereby a piece of DNA containing the mutated gene fragment flanked by large stretches of unaltered DNA is introduced into the ES cell through electroporation which is then incorporated into the genome at a targeted site. With the help of endogenous recombinases, the flanking unaltered sequences that line up with the homologous chromosomal DNA switch places with the genomic segment, taking along the mutated fragment between the arms. A wild-type...

References

Pharmacological and surgical options for the treatment of cervical dystonia. Neurology 55 S9-S14. Alexander, G.E., and M.D. Crutcher. 1990. Functional architecture of basal ganglia circuits neural substrates of parallel processing. Trends Neurosci. 13 266-271. Anderson, L.A., S.L. Hakojarvi, and S.K. Boudreaux. 1998. Zinc acetate treatment in Wilson's disease. Ann Pharmacotherapy 32 78-87. Ballard, P.A., J.W. Tetrud, and J.W. Langston. 1985. Permanent human...

Utility of 6Hydroxydopamine Lesioned Rats in the Preclinical Screening of Novel Treatments for Parkinson Disease

Parkinson disease PD is one of the most common neurodegenerative disorders, affecting about 1 of people over sixty years of age for review see Bezard et al. 2001 Dauer and Przedborski 2003 Fahn 2003 . The disease got its name from the English neurologist James Parkinson, who first described it in 1817 as a shaking palsy. The characteristic motor symptoms of PD consist of resting tremor, rigidity, hypo- and bradykinesia, and postural abnormalities Gelb et al. 1999 . These symptoms are caused by...

Direct Lickforcerhythm Measurements In Rats And Mice

Quantitative characterization of rodents' licking probably began with the observations of Stellar and Hill 1952 , who arranged a low-current contact circuit for the electronic detection of individual tongue contacts as rats licked water from a sipper tube. They reported that lick rhythm, usually specified in Hz cycles per second , was 5-7 Hz. Their emphasis was on the constancy of this lick rhythm despite large variations in thirst. Since this early observation, it has become clear that lick...

Tremor Recording And Measurement

The neurophysiologic characterization of tremor begins with a measurement of tremor amplitude and frequency. Commercially available motion transducers can measure the force, displacement, velocity, and acceleration of tremor Elble and Deuschl 2002 . Miniature accelerometers are the most popular devices for recording tremor because they are lightweight lt 15 grams and very sensitive gt 6mV G G acceleration of gravity . However, most of these devices are sensitive to gravity, and this...

Transgenic Rodent Models of Huntington Disease

ROSS, and DAVID R. BORCHELT Have you ever had an exam question where the instructor told you that there was more than one correct answer The study of transgenic mouse models of Huntington disease HD is a classic example of such a situation. A number of investigators have asked whether a mouse that models this disease can be created and very few have used the same approach. The spectrum of answers provides insight into the molecular mechanisms of HD and other...

Case Frozen Addicts Nova

Mptp Parkinson

The discovery of MPTP has provided a useful model of Parkinsonism that appears to recapitulate the pathology of the disease seen in humans. The identification of MPTP may be one of the few cases in which a specific neurotoxin was discovered in humans first, followed by development of an animal model. The story first started around 1976 when a chemistry student named Barry Kidston was synthesizing a designer heroin, MPPP, for recreational use. Although generally successful, at one point he...

Nongenetic Causes

The etiologies of ET are likely to be both genetic and nongenetic 66,67 . Differences between the genetic and nongenetic forms of the disease have not been identified, other than a possibly younger age of onset in genetic forms of the disease 45 . One important question is the magnitude of a genetic contribution to the etiology of this disease on a population level. The literature commonly states that 50 of ET cases are attributed to genetic causes. This estimate appears to be based on the...

Genetic Susceptibility and Animal Modeling of PSP

PARVONEH POORKAJ NAVAS, IAN D'SOUZA, and GERARD D. SCHELLENBERG Progressive supranuclear palsy PSP is a neurodegener-ative disorder characterized by Parkinsonism, rigidity, pseudobulbar palsy, axial dystonia, postural instability, and supranuclear gaze palsy. PSP is generally a sporadic disorder however, familial clustering has been reported, suggesting that heritable genetic components contribute to the onset or progression of the disease. PSP is pathologically characterized by...

Historical Review

The term multiple system atrophy MSA was introduced by Graham and Oppenheimer in 1969 to denote a neurode-generative disease characterized clinically by any combination of autonomic, parkinsonian, cerebellar, or pyramidal symptoms and signs and pathologically by cell loss and gliosis in the basal ganglia and olivopontocerebellar system. Previously, cases of MSA were reported under the rubrics of olivopontocerebellar atrophy OPCA , idiopathic orthostatic hypotension IOH or progressive autonomic...

Kailash P Bhatia

HISTORICAL ASPECTS, CLASSIFICATION, AND DEFINITION OF PAROXYSMAL MOVEMENT DISORDERS Mount and Reback 1940 first used the term paroxysmal dystonic choreoathetosis PDC when reporting a 23-year-old man with attacks of choreo dystonia lasting many hours 1 . He was from a family with many others similarly affected 1 . In 1941, Smith and Heersema reported what they called periodic dystonia 2 their cases were probably similar to those of Kertesz 1967 , who introduced the new term paroxysmal...

Elegans Parkinson Disease Models Generated By Genetic Mutations

Among the earliest experiments performed on C. elegans were mutagenesis studies aimed at recovering visible phe-notypes. From these, the scoreable phenotypes included those with movement deficits and were defined as uncoordinated unc . Other deficits of neuromuscular origin were also described such as egg-laying defective egl and anterior body contraction and expulsion defective in defecation aex Iwasaki et al. 1997 . We have already mentioned the types of uncoordinated phenotypes. Slow and...

Elegans Parkinson Disease Models Generated By Transgenic Manipulations

Elegans Twitching

Researchers have also applied transgenic approaches to C. elegans Mello and Fire 1995 . We have produced a trans-genic Parkinson disease model in C. elegans using overexpression of a-synuclein Lakso et al. 2003 . The product of this gene is found in Lewy bodies, the pathological hallmark of Parkinson disease Spillantini et al. 1997 . Mutations in this gene lead to familial forms of Parkinson disease Poly-meropoulus et al. 1997 . Some of the biochemical features of Parkinson disease were...

T31

Arrests may also disturb and distort the repetitive movements. In everyday living bradykinesia manifests not only by overall slowness in volitional movement, but also by reduced frequency and fluidity of spontaneous movements such as crossing the legs when sitting, swinging the arms when walking, and making gestures during conversation. Individuals with bradykinesia also experience difficulty with tasks such as brushing the teeth, shampooing the hair, using a screwdriver, stirring liquids, and...

List of Contributors

Tetsuo Ashizawa, Department of Neurology, John Sealy Chair of Neurology, The University of Texas Medical Branch UTMB , Galveston, TX P.C. Baier, Department of Clinical Neurophysiology, Georg-August University Gottingen, Gottingen, Germany Lore Becker, Institut f r Diabetesforschung, Munich David J. Bennett, Professor, Division of Neuroscience, University of Alberta, Edmonton, Alberta, Canada Brett Berke, Department of Biological Sciences, University of Iowa, Iowa City, IA Ranjita Betarbet,...

Ronald F Pfeiffer

B2 MPTP-Induced Nigrostriatal Injury in Nonhuman Primates 139 JOEL S. PERLMUTTER and SAMER D. TABBAL B3 From Man to Mouse The MPTP Model of Parkinson Disease 149 VERNICE JACKSON-LEWIS and RICHARD JAY SMEYNE B4 Rotenone Rat and Other Neurotoxin Models of Parkinson Disease 161 TODD B. SHERER, RANJITA BETARBET, and J. TIMOTHY GREENAMYRE B5 Drosophila Models of Parkinson Disease 173 LEO J. PALLANCK and ALEXANDER J. WHITWORTH B6 Phenotypical Characterization of Genetic Mouse Models of Parkinson...