Motor and cognitive deficits in the heterozygous leaner mouse, a Cav2.1 voltage-gated Ca2+ channel mutant

NEUROBIOLOGY OF AGING

卷:29

Article

Alonso, Isabel^1,3  Marques, Joana M.²  Sousa, Nuno⁴  Sequeiros, Jorge^1,3  Olsson, I. Anna S.²  Silveira, Isabel¹ 

[1] Univ Porto, UnIGENe, IBMC, P-4150180 Oporto, Portugal

[2] Univ Porto, Lab Anim Sci Grp, IBMC, P-4150180 Oporto, Portugal

[3] Univ Porto, ICBAS, P-4150180 Oporto, Portugal

[4] Univ Minho, Life & Hlth Sci Res Inst ICVS, Neurosci Grp, P-4719 Braga, Portugal

关键词: rotarod test;    water maze test;    natural mutant;    calcium currents;    memory;    learning;   

DOI  :  10.1016/j.neurobiolaging.2007.04.005

来源: Elsevier

【 摘 要 】

The leaner mutation in mice affects the Ca(v)2.1 voltage-gated calcium channel alpha(1A)-subunit gene (Cacna1a), causing a reduction in calcium currents predominantly in Purkinje cells. This reduction in calcium currents causes severe progressive cerebellar ataxia, beginning around postnatal day 10, in homozygous leaner mice (tg(la)/tg(la)), while their heterozygous littermates (tg(la)/+) present no obvious behavioral deficits. In humans, heterozygous mutations in the Cacna1a orthologous gene produce a broad range of neurological manifestations. To evaluate the phenotypic status of the tg(la)/+ animals, we assessed motor performance and cognition, at different ages, in these mutant mice. We were able to observe age-dependent impairment in motor and cognitive tasks; balance and motor learning deficits were found in demanding tasks on the rotarod and on the hanging wire test, while spatial learning and memory impairment was observed in the Morris water maze. Progressive dysfunction in escape reflexes, indicative of neurological impairment, was also present in tg(la)/+ animals. Although not presenting major motor alterations, tg(la)/+ mice show age-dependent motor and cognitive deficits. (C) 2007 Elsevier Inc. All rights reserved.

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