CaV1.3 L-Type Calcium Channels Increase the Vulnerability of Substantia Nigra Dopaminergic Neurons in MPTP Mouse Model of Parkinson’s Disease
Autor: | Aditi Verma, Vijayalakshmi Ravindranath |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Aging Cognitive Neuroscience Substantia nigra Cav1.3 lcsh:RC321-571 03 medical and health sciences chemistry.chemical_compound alternative splicing 0302 clinical medicine Internal medicine medicine lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry MPTP biology Tyrosine hydroxylase Pars compacta Calcium channel Neurodegeneration neurodegeneration Brief Research Report medicine.disease SNpc Ventral tegmental area 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry nervous system biology.protein gene expression CaV1.342A 030217 neurology & neurosurgery Neuroscience |
Zdroj: | Frontiers in Aging Neuroscience Frontiers in Aging Neuroscience, Vol 11 (2020) |
ISSN: | 1663-4365 |
DOI: | 10.3389/fnagi.2019.00382 |
Popis: | Mechanisms underlying the selective vulnerability of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) over those in the ventral tegmental area (VTA) to degeneration in Parkinson's disease (PD) remain poorly understood. DA neurons of SNpc and VTA are autonomous pacemakers but pacemaking in SNpc but not in VTA is accompanied by calcium influx through L-type calcium channel, CaV1.3 contributing to increased intracellular calcium and hence to cell death. CaV1.342A, an alternatively spliced short variant of CaV1.3 has increased calcium influx. We, therefore studied the role of CaV1.342 (full-length channel) and CaV1.342A in mouse SNpc in PD pathogenesis by quantifying mRNA levels of CaV1.342 and CaV1.342A in SNpc and followed the change in their levels in MPTP induced parkinsonism mouse model. Using in situ hybridization and immunohistochemistry we observed the localization of mRNA of CaV1.342 and CaV1.342A in tyrosine hydroxylase (TH) positive DA neurons. Further, mRNA levels of CaV1.342A were higher in SNpc as compared to the cortex. Upon MPTP treatment, mRNA levels of CaV1.342 and CaV1.342A maintained their levels in SNpc in spite of the loss of ~50% of the DA neurons. This indicates that the expression of CaV1.342 and CaV1.342A is maintained at a robust level during the degenerative process in the parkinsonism model. |
Databáze: | OpenAIRE |
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