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| Content Provider | Springer Nature Link |
|---|---|
| Author | Bawa, Bhupinder Abbott, Louise C. |
| Copyright Year | 2008 |
| Abstract | Ca$_{v}$ 2.1 voltage-gated calcium channels (VGCC) are highly expressed by cerebellar neurons, and their dysfunction is linked to human disorders including familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6. Altered calcium homeostasis, due to dysfunctional Ca$_{v}$ 2.1 VGCC can severely affect mitochondrial function, eventually leading to neuronal cell death. We study leaner and tottering mice, which carry autosomal recessive mutations in the gene coding for the α$_{1A pore-forming}$ subunit of Ca$_{v}$ 2.1 VGCC. Both leaner and tottering mice exhibit cerebellar ataxia and epilepsy. Excessive leaner cerebellar granule cell (CGC) death starts soon after postnatal day 10, but it is not known whether the degree of CGC cell death observed in adult leaner mice is significantly different from wild type mice. We used Fluoro-Jade and TUNEL staining to quantify apoptotic cell death in leaner and wild type CGC. We investigated calcium homeostasis, mitochondrial function and generation of reactive oxygen species (ROS) in isolated CGC, using indicator dyes Fura-2AM, TMRM and CMH$_{2}$DCFDA, respectively. We observed a small but significant increase in number of apoptotic adult leaner CGC. Calcium homeostasis and mitochondrial function also were altered in leaner CGC. However, no significant differences in ROS levels were observed. It is possible that CGC death in leaner mice may be related to mitochondrial dysfunction but may not be directly related to decreased basal intracellular calcium. |
| Starting Page | 1 |
| Ending Page | 18 |
| Page Count | 18 |
| File Format | |
| ISSN | 10298428 |
| Journal | Neurotoxicity Research |
| Volume Number | 13 |
| Issue Number | 1 |
| e-ISSN | 14763524 |
| Language | English |
| Publisher | Springer-Verlag |
| Publisher Date | 2008-01-01 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Apoptosis Neurodegeneration Cerebellum Voltage-gated calcium ion channels Mitochondrial membrane potential Calcium ion homeostasis Leaner mutant mice Neurosciences Pharmaceutical Sciences/Technology Neurology Neurochemistry Pharmacology/Toxicology Neurobiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Toxicology |
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