scholarly journals A Single Dopamine Pathway Underlies Progressive Locomotor Deficits in a Drosophila Model of Parkinson Disease

Cell Reports ◽  
2013 ◽  
Vol 5 (4) ◽  
pp. 952-960 ◽  
Author(s):  
Thomas Riemensperger ◽  
Abdul-Raouf Issa ◽  
Ulrike Pech ◽  
Hélène Coulom ◽  
Mỹ-Vân Nguyễn ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Drosophila Model ◽  
Locomotor Deficits

scholarly journals ­Bcl-2 homologue debcl enhances α-synuclein-induced phenotypes in Drosophila

2016 ◽  
Author(s):  
Peter G M'Angale ◽  
Brian E Staveley
Keyword(s):  
Parkinson Disease ◽  
Dopaminergic Neurons ◽  
Neuronal Degeneration ◽  
Altered Expression ◽  
Drosophila Model ◽  
Age Dependent ◽  
Climbing Ability ◽  
The Common ◽  
Locomotor Ability

Background Parkinson disease (PD) is a debilitating movement disorder that afflicts 1 to 2% of the population over 50 years of age. The common hallmark for both sporadic and familial forms of PD is mitochondrial dysfunction. Mammals have at least twenty proapoptotic and antiapoptotic Bcl-2 family members, in contrast, only two Bcl-2 family genes have been identified in Drosophila melanogaster, the proapoptotic mitochondrial localized debcl and the antiapoptotic Buffy. The expression of α-synuclein, the first gene identified to contribute to inherited forms of PD, in the dopaminergic neurons (DA) of flies has provided a robust and well-studied Drosophila model of PD complete with the loss of neurons and accompanying motor defects. The altered expression of debcl in the DA neurons and neuron-rich eye and along with the expression of α-synuclein offers an opportunity to highlight the role of debcl in mitochondrial-dependent neuronal degeneration and death. Results The directed overexpression of debcl using the Ddc-Gal4 transgene in the dopaminergic neurons of Drosophila resulted in flies with severely decreased survival and a premature age-dependent loss in climbing ability. The inhibition of debcl resulted in enhanced survival and improved climbing ability whereas the overexpression of debcl in the α-synuclein-induced Drosophila model of PD resulted in more severe phenotypes. In addition, the co-expression of debcl along with Buffy partially counteracts the debcl-induced phenotypes, to improve the lifespan and the associated loss of locomotor ability observed. In complementary experiments, the overexpression of debcl along with the expression of α-synuclein in the eye, enhanced the eye ablation that results from the overexpression of debcl. The co-expression of Buffy along with debcl overexpression results in the rescue of the moderate developmental eye defects. The co-expression of Buffy along with inhibition of debcl partially restores the eye to a roughened eye phenotype. Discussion The overexpression of debcl in DA neurons produces flies with shortened lifespan and impaired locomotor ability, phenotypes that are strongly associated with models of PD in Drosophila. The co-expression of debcl along with α-synuclein enhanced the Parkinson disease-like phenotypes. The co-expression of debcl along with Buffy suppresses these phenotypes. Complementary experiments in the Drosophila eye show similar trends during development. Taken all together these results suggest a role for debcl in neurodegenerative disorders.

scholarly journals Laryngeal muscle biology in thePink1−/−rat model of Parkinson disease

2019 ◽  
Vol 126 (5) ◽  
pp. 1326-1334 ◽  
Author(s):  
Tiffany J. Glass ◽  
Cynthia A. Kelm-Nelson ◽  
John A. Russell ◽  
John C. Szot ◽  
Jacob M. Lake ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Rat Model ◽  
Force Production ◽  
Laryngeal Function ◽  
Laryngeal Muscle ◽  
Myosin Heavy Chain Isoform ◽  
Section Size ◽  
Neural Cell Adhesion ◽  
Muscle Biology ◽  
Locomotor Deficits

Neuromuscular pathology is found in the larynx and pharynx in humans with Parkinson disease (PD); however, it is unknown when this pathology emerges. We hypothesized that pathology occurs in early (premanifest) stages. To address this, we used the Pink1−/− rat model of PD, which shows age-dependent dopaminergic neuron loss, locomotor deficits, and deficits related to laryngeal function. We report findings in the thyroarytenoid muscle (TA) in Pink1−/− rats compared with wild-type (WT) control rats at 4 and 6 mo of age. TAs were analyzed for force production, myosin heavy chain isoform (MyHC), centrally nucleated myofibers, neural cell adhesion molecule, myofiber size, and muscle section size. Compared with WT, Pink1−/− TA had reductions in force levels at 1-Hz stimulation and 20-Hz stimulation, increases in relative levels of MyHC 2L, increases in incidence of centrally nucleated myofibers in the external division of the TA, and reductions in myofiber size of the vocalis division of the TA at 6 mo of age. Alterations of laryngeal muscle biology occur in a rat model of premanifest PD. Although these alterations are statistically significant, their functional significance remains to be determined.NEW & NOTEWORTHY Pathology of peripheral nerves and muscle has been reported in the larynx and pharynx of humans diagnosed with Parkinson disease (PD); however, it is unknown whether differences of laryngeal muscle occur at premanifest stages. This study examined the thyroarytenoid muscles of the Pink1−/− rat model of PD for differences of muscle biology compared with control rats. Thyroarytenoid muscles of Pink1−/− rats at premanifest stages show differences in multiple measures of muscle biology.

scholarly journals Modulation of subthalamic T-type Ca2+ channels remedies locomotor deficits in a rat model of Parkinson disease

2011 ◽  
Vol 121 (8) ◽  
pp. 3289-3305 ◽  
Author(s):  
Chun-Hwei Tai ◽  
Ya-Chin Yang ◽  
Ming-Kai Pan ◽  
Chen-Syuan Huang ◽  
Chung-Chin Kuo
Keyword(s):  
Parkinson Disease ◽  
Rat Model ◽  
Locomotor Deficits ◽  
Ca2 Channels

scholarly journals Persistent Short-Term Memory Defects Following Sleep Deprivation in a Drosophila Model of Parkinson Disease

SLEEP ◽  
2009 ◽  
Vol 32 (8) ◽  
pp. 984-992 ◽  
Author(s):  
Laurent Seugnet ◽  
James E. Galvin ◽  
Yasuko Suzuki ◽  
Laura Gottschalk ◽  
Paul J. Shaw
Keyword(s):  
Sleep Deprivation ◽  
Parkinson Disease ◽  
Short Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Drosophila Model

scholarly journals ­Bcl-2 homologue debcl enhances α-synuclein-induced phenotypes in Drosophila

2016 ◽  
Author(s):  
Peter G M'Angale ◽  
Brian E Staveley
Keyword(s):  
Parkinson Disease ◽  
Dopaminergic Neurons ◽  
Neuronal Degeneration ◽  
Altered Expression ◽  
Drosophila Model ◽  
Age Dependent ◽  
Climbing Ability ◽  
The Common ◽  
Locomotor Ability

Background Parkinson disease (PD) is a debilitating movement disorder that afflicts 1 to 2% of the population over 50 years of age. The common hallmark for both sporadic and familial forms of PD is mitochondrial dysfunction. Mammals have at least twenty proapoptotic and antiapoptotic Bcl-2 family members, in contrast, only two Bcl-2 family genes have been identified in Drosophila melanogaster, the proapoptotic mitochondrial localized debcl and the antiapoptotic Buffy. The expression of α-synuclein, the first gene identified to contribute to inherited forms of PD, in the dopaminergic neurons (DA) of flies has provided a robust and well-studied Drosophila model of PD complete with the loss of neurons and accompanying motor defects. The altered expression of debcl in the DA neurons and neuron-rich eye and along with the expression of α-synuclein offers an opportunity to highlight the role of debcl in mitochondrial-dependent neuronal degeneration and death. Results The directed overexpression of debcl using the Ddc-Gal4 transgene in the dopaminergic neurons of Drosophila resulted in flies with severely decreased survival and a premature age-dependent loss in climbing ability. The inhibition of debcl resulted in enhanced survival and improved climbing ability whereas the overexpression of debcl in the α-synuclein-induced Drosophila model of PD resulted in more severe phenotypes. In addition, the co-expression of debcl along with Buffy partially counteracts the debcl-induced phenotypes, to improve the lifespan and the associated loss of locomotor ability observed. In complementary experiments, the overexpression of debcl along with the expression of α-synuclein in the eye, enhanced the eye ablation that results from the overexpression of debcl. The co-expression of Buffy along with debcl overexpression results in the rescue of the moderate developmental eye defects. The co-expression of Buffy along with inhibition of debcl partially restores the eye to a roughened eye phenotype. Discussion The overexpression of debcl in DA neurons produces flies with shortened lifespan and impaired locomotor ability, phenotypes that are strongly associated with models of PD in Drosophila. The co-expression of debcl along with α-synuclein enhanced the Parkinson disease-like phenotypes. The co-expression of debcl along with Buffy suppresses these phenotypes. Complementary experiments in the Drosophila eye show similar trends during development. Taken all together these results suggest a role for debcl in neurodegenerative disorders.

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