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Myoclonic Epilepsy and Ragged Red Fibers (MERRF) Syndrome: Selective Vulnerability of CNS Neurons Does Not Correlate with the Level of Mitochondrial tRNA^(lys) Mutation in Individual Neuronal Isolates

Zhou, Li and Chomyn, Anne and Attardi, Giuseppe and Miller, Carol A. (1997) Myoclonic Epilepsy and Ragged Red Fibers (MERRF) Syndrome: Selective Vulnerability of CNS Neurons Does Not Correlate with the Level of Mitochondrial tRNA^(lys) Mutation in Individual Neuronal Isolates. Journal of Neuroscience, 17 (20). pp. 7746-7753. ISSN 0270-6474. PMCID PMC6793887. https://resolver.caltech.edu/CaltechAUTHORS:20191030-134818569

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Abstract

Selective vulnerability of subpopulations of neurons is a striking feature of neurodegeneration. Mitochondrially transmitted diseases are no exception. In this study CNS tissues from a patient with myoclonus epilepsy and ragged red fibers (MERRF) syndrome, which results from an A to G transition of nucleotide (nt) 8344 in the mitochondrial tRNA^(Lys) gene, were examined for the proportion of mutant mtDNA. Either individual neuronal somas or the adjacent neuropil and glia were microdissected from cryostat tissue sections of histologically severely affected brain regions, including dentate nuclei, Purkinje cells, and inferior olivary nuclei, and from a presumably less affected neuronal subpopulation, the anterior horn cells of the spinal cord. Mutant and normal mtDNA were quantified after PCR amplification with a mismatched primer and restriction enzyme digestion. Neurons and the surrounding neuropil and glia from all CNS regions that were analyzed exhibited high proportions of mutant mtDNA, ranging from 97.6 ± 0.7% in Purkinje cells to 80.6 ± 2.8% in the anterior horn cells. Within each neuronal group that was analyzed, neuronal soma values were similar to those in the surrounding neuropil and glia or in the regional tissue homogenate. Surprisingly, as compared with controls, neuronal loss ranged from 7% of the Purkinje cells to 46% of the neurons of the dentate nucleus in MERRF cerebellum. Thus, factors other than the high proportion of mutant mtDNA, in particular nuclear-controlled neuronal differences among various regions of the CNS, seem to contribute to the mitochondrial dysfunction and ultimate cell death.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1523/jneurosci.17-20-07746.1997DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6793887PubMed CentralArticle
Additional Information:© 1997 Society for Neuroscience. Received Feb. 27, 1997; revised July 15, 1997; accepted July 30, 1997. These studies were supported by Grants from the National Institute of Aging (P50-AG05142) and the National Institute of Mental Health (5R37-MH39145) to C.A.M. and from the National Institute of General Medical Sciences (GM-11726) to G.A. We are grateful to Ms. Jeanette Espinosa and Carol Church for their excellent secretarial assistance, to Dr. Roger Duncan of the School of Pharmacy, University of Southern California, for assistance with quantitative densitometry, and to Drs. Karen Jain and Terence Sanger for helpful discussions.
Funders:
Funding AgencyGrant Number
National Institute of AgingUNSPECIFIED
NIHP50-AG05142
NIH5R37-MH39145
National Institute of Mental Health (NIMH)UNSPECIFIED
NIHGM-11726
National Institute of General Medical SciencesUNSPECIFIED
Subject Keywords:MERRF syndrome; CNS microdissection; PCR; neurodegeneration; tRNA^(Lys); mtDNA
Issue or Number:20
PubMed Central ID:PMC6793887
Record Number:CaltechAUTHORS:20191030-134818569
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20191030-134818569
Official Citation:Myoclonic Epilepsy and Ragged Red Fibers (MERRF) Syndrome: Selective Vulnerability of CNS Neurons Does Not Correlate with the Level of Mitochondrial tRNAlys Mutation in Individual Neuronal Isolates. Li Zhou, Anne Chomyn, Giuseppe Attardi, Carol A. Miller. Journal of Neuroscience 15 October 1997, 17 (20) 7746-7753; DOI: 10.1523/JNEUROSCI.17-20-07746.1997
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99561
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:30 Oct 2019 21:50
Last Modified:30 Oct 2019 21:50

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