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Calcium CaV1 Channel Subtype mRNA Expression in Parkinson’s Disease Examined by In Situ Hybridization

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Abstract

The factors which make some neurons vulnerable to neurodegeneration in Parkinson’s disease while others remain resistant are not fully understood. Studies in animal models of Parkinson’s disease suggest that preferential use of CaV1.3 subtypes by neurons may contribute to the neurodegenerative process by increasing mitochondrial oxidant stress. This study quantified the level of mRNA for the CaV1 subtypes found in the brain by in situ hybridization using CaV1 subtype-specific [35S]-radiolabelled oligonucleotide probes. In normal brain, the greatest amount of messenger RNA (mRNA) for each CaV1 subtype was found in the midbrain (substantia nigra), with a moderate level in the pons (locus coeruleus) and lower quantities in cerebral cortex (cingulate and primary motor). In Parkinson’s disease, the level of CaV1 subtype mRNA was maintained in the midbrain and pons, despite cell loss in these areas. In cingulate cortex, CaV1.2 and CaV1.3 mRNA increased in cases with late-stage Parkinson’s disease. In primary motor cortex, the level of CaV1.2 mRNA increased in late-stage Parkinson’s disease. The level of CaV1.3 mRNA increased in primary motor cortex of cases with early-stage Parkinson’s disease and normalized to near the control level in cases from late-stage Parkinson’s disease. The finding of elevated CaV1 subtype expression in cortical brain regions supports the view that disturbed calcium homeostasis is a feature of Parkinson’s disease throughout brain and not only a compensatory consequence to the neurodegenerative process in areas of cell loss.

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Acknowledgments

The Cure Parkinson’s Trust (registered charity number 1111816) funded this work. The Parkinson’s UK Tissue Bank, which is funded by Parkinson’s UK (registered charity 258197 in England and Wales and SC037554 in Scotland), supplied the tissue samples and associated clinical and neuropathological data.

Conflict of Interest

The authors declare that there are no conflicts of interest associated with this work.

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Authors and Affiliations

  1. Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Department of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK

    Michael J. Hurley & David T. Dexter

  2. Neuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, Charing Cross Campus, St Dunstan’s Road, London, W6 8RP, UK

    Steve M. Gentleman

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  1. Michael J. Hurley
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Correspondence to Michael J. Hurley.

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Hurley, M.J., Gentleman, S.M. & Dexter, D.T. Calcium CaV1 Channel Subtype mRNA Expression in Parkinson’s Disease Examined by In Situ Hybridization. J Mol Neurosci 55, 715–724 (2015). https://doi.org/10.1007/s12031-014-0410-8

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  • DOI: https://doi.org/10.1007/s12031-014-0410-8

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