Evidence for a Dissociation between MPTP Toxicity and Tyrosinase Activity Based on Congenic Mouse Strain Susceptibility

Hofele, Katja; Sedelis, Marco; Auburger, Georg; Morgan, Sarah; Huston, Joseph P.; Schwarting, Rainer K.W.

doi:10.1006/exnr.2000.7588

Cited by 31 publications

(17 citation statements)

References 31 publications

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“…Orofacial shredding is an important motor behavior involved in nest building, a natural mouse behavior related to thermoregulation and pup survival (Lynch, 1980;Broida and Svare, 1982;Crawley, 2000). Both male and female mice shred material to build nests, and analysis of shredding behavior has been used to assess nigrostriatal sensorimotor function in rodents Sedelis et al, 2000;Hofele et al, 2001;Szczypka et al, 2001). The behavior requires the use of orofacial and forelimb movements, where animals pull the nesting material apart with their forelimbs and teeth and then breakdown the material in their mouths and incorporate it into their bedding.…”

Section: Methodsmentioning

confidence: 99%

“…Because ASO mice overexpress normal human ␣-synuclein, which in humans causes early onset familial PD (Singleton et al, 2003), we focused on tests sensitive to dopaminergic dysfunction, a hallmark of PD Ogawa et al, 1985Ogawa et al, , 1987Matsuura et al, 1997;Sedelis et al, 2000;Hofele et al, 2001;Szczypka et al, 2001;Tillerson and Miller, 2003). We have shown previously that mice with a loss of dopaminergic neurons caused by a defect in Pitx3 show similar alterations to ASO mice in several of these tests, and in most cases these alterations are reversed by L-DOPA (Hwang et al, 2003(Hwang et al, , 2004.…”

Section: Role Of the Nigrostriatal System In Sensorimotor Deficits Inmentioning

confidence: 99%

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Early and Progressive Sensorimotor Anomalies in Mice Overexpressing Wild-Type Human α-Synuclein

Fleming¹,

Salcedo²,

Fernagut³

et al. 2004

J. Neurosci.

440

467

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Accumulation of ␣-synuclein in brain is a hallmark of synucleinopathies, neurodegenerative diseases that include Parkinson's disease. Mice overexpressing ␣-synuclein under the Thy-1 promoter (ASO) show abnormal accumulation of ␣-synuclein in cortical and subcortical regions of the brain, including the substantia nigra. We examined the motor deficits in ASO mice with a battery of sensorimotor tests that are sensitive to alterations in the nigrostriatal dopaminergic system. Male wild-type and ASO mice were tested every 2 months for 8 months for motor performance and coordination on a challenging beam, inverted grid, and pole, sensorimotor deficits in an adhesive removal test, spontaneous activity in a cylinder, and gait. Fine motor skills were assessed by the ability to grasp cotton from a bin. ASO mice displayed significant impairments in motor performance and coordination and a reduction in spontaneous activity as early as 2 months of age. Motor performance and coordination impairments became progressively worse with age and sensorimotor deficits appeared at 6 months. Fine motor skills were altered at 4 months and worsened at 8 months. These data indicate that overexpression of ␣-synuclein induced an early and progressive behavioral phenotype that can be detected in multiple tests of sensorimotor function. These behavioral deficits provide a useful way to assess novel drug therapy in genetic models of synucleinopathies.

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Section: Methodsmentioning

confidence: 99%

Section: Role Of the Nigrostriatal System In Sensorimotor Deficits Inmentioning

confidence: 99%

Early and Progressive Sensorimotor Anomalies in Mice Overexpressing Wild-Type Human α-Synuclein

Fleming¹,

Salcedo²,

Fernagut³

et al. 2004

J. Neurosci.

440

467

View full text Add to dashboard Cite

show abstract

“…4.3.5. Cotton Shred-Both male and female mice shred cotton material to build nests, and analysis of shredding behavior has been used to assess nigrostriatal sensorimotor function in rodents (Fleming et al, 2004;Hofele et al, 2001;Sedelis et al, 2000;Szczypka et al, 2001;Upchurch and Schallert 1983). The behavior requires the use of orofacial and forelimb movements.…”

Section: Pole Test-mentioning

confidence: 99%

Motor deficits and altered striatal gene expression in aphakia (ak) mice

et al. 2007

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Like humans with Parkinsons disease (PD), the ak mouse lacks the majority of the substantia nigra pars compacta (SNc) and experiences striatal denervation. The purpose of this study was to test whether motor abnormalities in the ak mouse progress over time, and whether motor function could be associated with temporal alterations in the striatal transcriptome. Ak and wt mice (28 to 180 days old) were tested using paradigms sensitive to nigrostriatal dysfunction. Results were analyzed using a linear mixed model. Ak mice significantly underperformed wt controls in rotarod, balance beam, string test, pole test and cotton shred tests at all ages examined. Motor performance in ak mice remained constant over the first 6 months of life, with the exception of the cotton shred test, in which ak mice exhibited marginal decline in performance. Dorsal striatal semi-quantitative RT-PCR for 19 dopaminergic, cholinergic, glutaminergic and catabolic genes was performed in 1 and 6 month old groups of ak and wt mice. Preproenkephalin levels in ak mice were elevated in both age groups. Drd1, 3 and 4 levels declined over time, in contrast to increasing Drd2 expression. Additional findings included decreased Chrnα6 expression and elevated VGluT1 expression at both time points in ak mice, and elevated AchE expression in young ak mice only. Results confirm that motor ability does not decline significantly for the first 6 months of life in ak mice. Their striatal gene expression patterns are consistent with dopaminergic denervation, and change over time, despite relatively unaltered motor performance.

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“…In novel surroundings, when there is motivation to return to the home cage, rearing presumably facilitates spatial orientation through improved visual and olfactory surveillance. Rearing is decreased by depleting brain dopamine (Hofele et al, 2001) and with benzodiazepines or 5-HT1A agonists (Tsuji et al, 2000). Rearing is increased by ␣-2 adrenoreceptor antagonists (Delini-Stula, 1984) and dopamine D2 receptor agonists (Starr and Starr, 1986).…”

Section: Behavioral Correlates Of Serum Antibody Responses To Gabhs Imentioning

confidence: 99%

A Murine Model for Neuropsychiatric Disorders Associated with Group A β-Hemolytic Streptococcal Infection

Hoffman¹,

Hornig²,

Yaddanapudi³

et al. 2004

J. Neurosci.

113

123

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A syndrome of motoric and neuropsychiatric symptoms comprising various elements, including chorea, hyperactivity, tics, emotional lability, and obsessive-compulsive symptoms, can occur in association with group A ␤-hemolytic streptococcal (GABHS) infection. We tested the hypothesis that an immune response to GABHS can result in behavioral abnormalities. Female SJL/J mice were immunized and boosted with a GABHS homogenate in Freund's adjuvant, whereas controls received Freund's adjuvant alone. When sera from GABHSimmunized mice were tested for immunoreactivity to mouse brain, a subset was found to be immunoreactive to several brain regions, including deep cerebellar nuclei (DCN), globus pallidus, and thalamus. GABHS-immunized mice having serum immunoreactivity to DCN also had increased IgG deposits in DCN and exhibited increased rearing behavior in open-field and hole-board tests compared with controls and with GABHS-immunized mice lacking serum anti-DCN antibodies. Rearing and ambulatory behavior were correlated with IgG deposits in the DCN and with serum immunoreactivity to GABHS proteins in Western blot. In addition, serum from a GABHS mouse reacted with normal mouse cerebellum in nondenaturing Western blots and immunoprecipitated C4 complement protein and ␣-2-macroglobulin. These results are consistent with the hypothesis that immune response to GABHS can result in motoric and behavioral disturbances and suggest that anti-GABHS antibodies cross-reactive with brain components may play a role in their pathophysiology.

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Evidence for a Dissociation between MPTP Toxicity and Tyrosinase Activity Based on Congenic Mouse Strain Susceptibility

Cited by 31 publications

References 31 publications

Early and Progressive Sensorimotor Anomalies in Mice Overexpressing Wild-Type Human α-Synuclein

Early and Progressive Sensorimotor Anomalies in Mice Overexpressing Wild-Type Human α-Synuclein

Motor deficits and altered striatal gene expression in aphakia (ak) mice

A Murine Model for Neuropsychiatric Disorders Associated with Group A β-Hemolytic Streptococcal Infection

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