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Neurobehavioral performances and brain regional metabolism in Dab1scm (scrambler) mutant mice

Abstract : As disabled-1 (DAB1) protein acts downstream in the reelin signaling pathway modulating neuronal migration, glutamate neurotransmission, and cytoskeletal function, the disabled-I gene mutation (scrambler or Dab lscm mutation) results in ataxic mice displaying dramatic neuroanatomical defects similar to those observed in the reeler gene (Rein) mutation. By comparison to non-ataxic controls, Dab1(scm) mutants showed severe motor coordination impairments on stationary beam, coat-hanger, and rotorod tests but were more active in the open-field. Dab1(scm) mutants were also less anxious in the elevated plus-maze but with higher latencies in the emergence test. In mutants versus controls, changes in regional brain metabolism as measured by cytochrome oxidase (COX) activity occurred mainly in structures intimately connected with the cerebellum, in basal ganglia, in limbic regions, particularly hippocampus, as well as in visual and parietal sensory cortices. Although behavioral results characterized a major cerebellar disorder in the Dab1(scm) mutants, motor activity impairments in the open-field were associated with COX activity changes in efferent basal ganglia structures such as the substantia nigra, pars reticulata. Metabolic changes in this structure were also associated with the anxiety changes observed in the elevated plus-maze and emergence test. These results indicate a crucial participation of the basal ganglia in the functional phenotype of ataxic Dab ism mutants.
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Submitted on : Thursday, March 2, 2017 - 10:07:27 AM
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C. Jacquelin, R. Lalonde, C. Jantzen-Ossola, C. Strazielle. Neurobehavioral performances and brain regional metabolism in Dab1scm (scrambler) mutant mice. Behavioural Brain Research, 2013, 252, pp.92-100. ⟨10.1016/j.bbr.2013.05.024⟩. ⟨hal-01481013⟩



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