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7 results on '"De Lagran, M. Martinez"'

4. Haploinsufficiency of Dyrk1A in mice leads to specific alterations in the development and regulation of motor activity

Author

Fotaki, V., de Lagran, M. Martinez, Estivill, X., Arbones, M., and Dierssen M.

Subjects
Motor ability -- Research, Protein kinases -- Research, Health, Psychology and mental health
Abstract

DYRK1A is a protein kinase proposed to be involved in neurogenesis. Gene-targeting disruption of Dyrk1A in mice leads to decreased body and brain size, with no severe disturbance of behavior. In this study, the authors focused on the motor profile of [Dyrk1A.sup.+/-] mice. These mice presented impairment of neuromotor development with decreased activity, suggesting a physiological role of Dyrk1A in the maturation of the neuromotor system. In the adult, a marked hypoactivity and alteration of specific motor parameters were detected. These results are in agreement with the significant expression of Dyrk1A in structures related to motor function and support a role of Dyrk1A in the control of motor function.

Published
2004

6. Dopaminergic deficiency in mice with reduced levels of the dual-specificity tyrosine-phosphorylated and regulated kinase 1A, Dyrk1A+/−.

Author

De Lagran, M. Martinez, Bortolozzi, A., Millan, O., Gispert, J. D., Gonzalez, J. R., Arbones, M. L., Artigas, F., and Dierssen, M.

Subjects
*NERVOUS system, *DOPAMINE, *TYROSINE, *POSITRON emission tomography, *MOTOR ability
Abstract

The dual-specificity tyrosine-phosphorylated and regulated kinase 1A ( DYRK1A) gene encodes a protein kinase known to play a critical role in neurodevelopment. Mice with one functional copy of Dyrk1A (Dyrk1A+/−) display a marked hypoactivity and altered gait dynamics in basal conditions and in novel environments. Dopamine (DA) is a key neurotransmitter in motor behavior and genetic deletion of certain genes directly related to the dopaminergic system has a strong impact on motor activity. We have studied the effects of reduced Dyrk1A expression on the function of the nigrostriatal dopaminergic system. To characterize the dopaminergic system in DYRK1A+/− mice, we have used behavioral, pharmacological, histological, neurochemical and neuroimaging (microPET) techniques in a multidisciplinary approach. Dyrk1A+/− mice exhibited decreased striatal DA levels, reduced number of DA neurons in the substantia nigra pars compacta, as well as altered behavioral responses to dopaminergic agents. Moreover, microdialysis experiments revealed attenuated striatal DA release and positron emission tomography scan display reduced forebrain activation when challenged with amphetamine, in Dyrk1A+/− compared with wild-type mice. These data indicate that Dyrk1A is essential for a proper function of nigrostriatal dopaminergic neurons and suggest that Dyrk1A+/− mice can be used to study the pathogenesis of motor disorders involving dopaminergic dysfunction. [ABSTRACT FROM AUTHOR]

Published
2007
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7. Dopaminergic deficiency in mice with reduced levels of the dual-specificity tyrosine-phosphorylated and regulated kinase 1A, Dyrk1A+/−.

Author

De Lagran, M. Martinez, Bortolozzi, A., Millan, O., Gispert, J. D., Gonzalez, J. R., Arbones, M. L., Artigas, F., and Dierssen, M.

Subjects
NERVOUS system, DOPAMINE, TYROSINE, POSITRON emission tomography, MOTOR ability
Abstract

The dual-specificity tyrosine-phosphorylated and regulated kinase 1A ( DYRK1A) gene encodes a protein kinase known to play a critical role in neurodevelopment. Mice with one functional copy of Dyrk1A (Dyrk1A+/−) display a marked hypoactivity and altered gait dynamics in basal conditions and in novel environments. Dopamine (DA) is a key neurotransmitter in motor behavior and genetic deletion of certain genes directly related to the dopaminergic system has a strong impact on motor activity. We have studied the effects of reduced Dyrk1A expression on the function of the nigrostriatal dopaminergic system. To characterize the dopaminergic system in DYRK1A+/− mice, we have used behavioral, pharmacological, histological, neurochemical and neuroimaging (microPET) techniques in a multidisciplinary approach. Dyrk1A+/− mice exhibited decreased striatal DA levels, reduced number of DA neurons in the substantia nigra pars compacta, as well as altered behavioral responses to dopaminergic agents. Moreover, microdialysis experiments revealed attenuated striatal DA release and positron emission tomography scan display reduced forebrain activation when challenged with amphetamine, in Dyrk1A+/− compared with wild-type mice. These data indicate that Dyrk1A is essential for a proper function of nigrostriatal dopaminergic neurons and suggest that Dyrk1A+/− mice can be used to study the pathogenesis of motor disorders involving dopaminergic dysfunction. [ABSTRACT FROM AUTHOR]

Published
2007
Full Text
View/download PDF

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