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Spinal cord mitochondria display lower calcium retention capacity compared with brain mitochondria without inherent differences in sensitivity to cyclophilin D inhibition

Morota, Saori; Hansson, Magnus LU ; Ishii, Nagao; Kudo, Yoshihisa; Elmer, Eskil LU and Uchino, Hiroyuki (2007) In Journal of Neurochemistry 103(5). p.2066-2076
Abstract
The mitochondrial permeability transition (mPT) is a potential pathogenic mechanism in neurodegeneration. Varying sensitivity to calcium-induced mPT has been demonstrated for regions within the CNS possibly correlating with vulnerability following insults. The spinal cord is selectively vulnerable in e.g. amyotrophic lateral sclerosis and increased mPT sensitivity of mitochondria derived from the spinal cord has previously been demonstrated. In this study, we introduce whole-body hypothermia prior to removal of CNS tissue to minimize the effects of differential tissue extraction prior to isolation of spinal cord and cortical brain mitochondria. Spinal cord mitochondria were able to retain considerably less calcium when administered as... (More)
The mitochondrial permeability transition (mPT) is a potential pathogenic mechanism in neurodegeneration. Varying sensitivity to calcium-induced mPT has been demonstrated for regions within the CNS possibly correlating with vulnerability following insults. The spinal cord is selectively vulnerable in e.g. amyotrophic lateral sclerosis and increased mPT sensitivity of mitochondria derived from the spinal cord has previously been demonstrated. In this study, we introduce whole-body hypothermia prior to removal of CNS tissue to minimize the effects of differential tissue extraction prior to isolation of spinal cord and cortical brain mitochondria. Spinal cord mitochondria were able to retain considerably less calcium when administered as continuous infusion, which was not related to a general increased sensitivity of the mPT to calcium, its desensitization to calcium by the cyclophilin D inhibitor cyclosporin-A, or to differences in respiratory parameters. Spinal cord mitochondria maintained a higher concentration of extramitochondrial calcium during infusion than brain mitochondria possibly related to an increased set-point concentration for calcium uptake. A hampered transport and retention capacity of calcium may translate into an increased susceptibility of the spinal cord to neurodegenerative processes involving calcium-mediated damage. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cord injury, spinal, neurodegeneration, necrosis, ischemia, apoptosis, cell death
in
Journal of Neurochemistry
volume
103
issue
5
pages
2066 - 2076
publisher
Wiley-Blackwell
external identifiers
  • wos:000250985200034
  • scopus:36248984867
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2007.04912.x
language
English
LU publication?
yes
id
d09ef558-3c4a-4655-8baa-253221ab8bd2 (old id 971877)
date added to LUP
2008-01-30 07:06:19
date last changed
2017-06-11 04:29:57
@article{d09ef558-3c4a-4655-8baa-253221ab8bd2,
  abstract     = {The mitochondrial permeability transition (mPT) is a potential pathogenic mechanism in neurodegeneration. Varying sensitivity to calcium-induced mPT has been demonstrated for regions within the CNS possibly correlating with vulnerability following insults. The spinal cord is selectively vulnerable in e.g. amyotrophic lateral sclerosis and increased mPT sensitivity of mitochondria derived from the spinal cord has previously been demonstrated. In this study, we introduce whole-body hypothermia prior to removal of CNS tissue to minimize the effects of differential tissue extraction prior to isolation of spinal cord and cortical brain mitochondria. Spinal cord mitochondria were able to retain considerably less calcium when administered as continuous infusion, which was not related to a general increased sensitivity of the mPT to calcium, its desensitization to calcium by the cyclophilin D inhibitor cyclosporin-A, or to differences in respiratory parameters. Spinal cord mitochondria maintained a higher concentration of extramitochondrial calcium during infusion than brain mitochondria possibly related to an increased set-point concentration for calcium uptake. A hampered transport and retention capacity of calcium may translate into an increased susceptibility of the spinal cord to neurodegenerative processes involving calcium-mediated damage.},
  author       = {Morota, Saori and Hansson, Magnus and Ishii, Nagao and Kudo, Yoshihisa and Elmer, Eskil and Uchino, Hiroyuki},
  issn         = {1471-4159},
  keyword      = {cord injury,spinal,neurodegeneration,necrosis,ischemia,apoptosis,cell death},
  language     = {eng},
  number       = {5},
  pages        = {2066--2076},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Spinal cord mitochondria display lower calcium retention capacity compared with brain mitochondria without inherent differences in sensitivity to cyclophilin D inhibition},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2007.04912.x},
  volume       = {103},
  year         = {2007},
}