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Open Journal of Neuroscience

ISSN: 2075-9088
Volume 5, 2017

Open Journal of Neuroscience, 2012, 2-2 [Research Article]

Reduced mitochondrial function but not mitochondrial mass in cerebellar granule cells of homozygous Ca(v) 2.1 mutant mice (leaner mice) at postnatal age 20

Bhupinder Bawa1,*, Louise C. Abbott2
1 Department of Diagnostic Medicine/Pathobiology, Kansas State University, College of  Veterinary Medicine, Manhattan, KS, USA
2 Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA

Corresponding Author & Address:

Bhupinder Bawa
Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-5601, USA; Email address: bbawa@vet.k-state.edu; Tel: +1 785 532 3789; Fax: +1 785 532 4039

Article History:
Published: 8th May, 2012   Accepted: 8th May, 2012
Received: 4th January, 2012   Revised:  9th April, 2012

© Bawa et al.; licensee Ross Science Publishers

ROSS Open Access articles will be distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided that the original work will always be cited properly.

Keywords: Cerebellar granule cell death, Mitochondrial membrane potential, leaner mice, ROS independent cell death


Mutation in the CACNA1A gene coding for the a1A pore forming subunit of voltage-gated P/Q type (Cav 2.1) calcium ion channel is associated with several human neurological disorders like familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia 6. We study leaner mouse which carry a similar mutation in CACNA1A gene. These mice exhibit severe cerebellar granule cell (CGC) death which peaks at postnatal day (P) 20. Previously we have shown that CGC of leaner mice have altered intracellular calcium homeostasis at P20. Alteration of calcium homeostasis is known to cause mitochondrial dysfunction which can result in cell death. In this study we have investigated the mitochondrial function by measuring mitochondrial membrane potential (Δψm) using TMRM dye. A reduced Δψm in leaner CGCs at P20 was observed as compared to age matched wild type CGCs. To confirm that reduced Δψm observed in leaner CGC is due to reduced mitochondrial function and not due to decreased mitochondrial mass, the latter was measured by quantifying mitochondrial specific phospholipid, cardiolipin in CGC and also by semi-quantifying mitochondrial specific protein, cytochrome C in whole cerebellum. Both the techniques demonstrated no change in mitochondrial mass in leaner CGC as compared to age matched wild type CGC confirming a reduced mitochondrial function in leaner CGC at P20. Further, generation of ROS was measured using CM-H2DCFDA dye. No change in generation of ROS was observed in leaner and wild type CGC at P20 indicating a mitochondrial specific and ROS independent mechanism of cell death in leaner CGCs.

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