Abstract：
:Leaner mice carry a homozygous, autosomal recessive mutation in the mouse CACNA1A gene encoding the Alpha1A subunit of P/Q-type calcium channels, which results in an out-of-frame splicing event in the carboxy terminus of the Alpha1A protein. Leaner mice exhibit severe ataxia, paroxysmal dyskinesia and absence seizures. Functional studies have revealed a marked decrease in calcium currents through leaner P/Q-type channels and altered neuronal calcium ion homeostasis in cerebellar Purkinje cells. Histopathological studies of leaner mice have revealed extensive postnatal cerebellar Purkinje and granule cell loss. We examined the temporospatial pattern of cerebellar granule cell death in the leaner mouse between postnatal days (P) 10 and 40. Our observations clearly indicate that leaner cerebellar granule cells die via an apoptotic process and that the peak time of neuronal death is P20. We did not observe a significant increase in microglial and astrocytic responses at P20, suggesting that glial responses are not a cause of neuronal cell death. We propose that the leaner cerebellar granule cell represents an in vivo animal model for low intracellular [Ca2+]-induced apoptosis. Since intracellular [Ca2+] is critical in the control of gene expression, it is quite likely that reduced intracellular [Ca2+] could activate a lethal cascade of altered gene expression leading to the apoptotic granule cell death in the leaner cerebellum.
journal_name
Neurotox Resjournal_title
Neurotoxicity researchauthors
Lau FC,Frank TC,Nahm SS,Stoica G,Abbott LCdoi
10.1007/BF03033437keywords:
subject
Has Abstractpub_date
2004-01-01 00:00:00pages
267-80issue
4eissn
1029-8428issn
1476-3524journal_volume
6pub_type
杂志文章abstract：:Melamine is an industrial chemical that can cause central nervous system disorders including excitotoxicity and cognitive impairment. Its illegal use in powdered baby formula was the focus of a milk scandal in China in 2008. One of our previous studies showed that melamine impaired glutamatergic transmission in rat hi...
journal_title：Neurotoxicity research
pub_type： 杂志文章
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更新日期：2018-02-01 00:00:00
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journal_title：Neurotoxicity research
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journal_title：Neurotoxicity research
pub_type： 杂志文章,评审
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更新日期：2005-10-01 00:00:00
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更新日期：2000-01-01 00:00:00
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pub_type： 杂志文章,多中心研究
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journal_title：Neurotoxicity research
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journal_title：Neurotoxicity research
pub_type： 临床试验,杂志文章,随机对照试验
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