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Caractérisation phénotypique, comportementale et neurochimique, de la souris mutante ataxique scrambler (Dab1scm)

Abstract : The Dab1scm scrambler mice is a cerebellar ataxic mutant spontaneously mutated for a gene encoding a protein of the reelin signaling pathway involved in the development and the plasticity of laminated structures such as the neocortex, the hippocampus, and the cerebellum. Our objective was to characterize the behavioral and neurochemical phenotype of the scrambler mice during postnatal developmental and adult stages. The first signs of cerebellar ataxia are observable as early as 8 days and increase during the 2nd and 3rd weeks of postnatal life. Adult mouse is characterized by a significant disturbance of motor coordination and a locomotor hyperactivity which increases ans becomes stereotyped (circling) when the animal was placed in water. Morris water maze and spontaneous alternation highlight deficiencies possibly caused by disorder of visuomotor control and disinhibitory processes. Brain regional metabolic activity measured by cytochrome oxidase is relatively preserved in the mutant cerebellum. However, it is impaired in various connected regions of the brainstem as well as in the hippocampus and some cortical regions. Circling behavior and hyperactivity, possibly caused by a neurochemical imbalance between acetylcholine and dopamine, were evaluated in a rotameter with or whithout prior injection of D2 receptor antagonist. In parallel, cholinergic innervation of the central nervous system measured by acetylcholinesterase activity is lower in the substantia nigra for which a partial disruption and loss of dopaminergic neurons is observed. Although the multiple alterations complicate the structuro-fonctional study of this mutant, results have clarified the scrambler phenotype by comparison with others mutants of the reelin pathway. This mutants are now subject to a growing interest in not only ataxia modeling but also some neurological and neuropsychiatric diseases
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Submitted on : Friday, March 30, 2018 - 9:58:04 AM
Last modification on : Tuesday, October 13, 2020 - 10:46:39 AM

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  • HAL Id : tel-01754692, version 1


Cécile Jacquelin. Caractérisation phénotypique, comportementale et neurochimique, de la souris mutante ataxique scrambler (Dab1scm). Médecine humaine et pathologie. Université de Lorraine, 2015. Français. ⟨NNT : 2015LORR0345⟩. ⟨tel-01754692⟩



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