Normal mitochondrial respiratory function is essential for spatial remote memory in mice

Daisuke Tanaka, Kazuto Nakada, Keizo Takao, Emi Ogasawara, Atsuko Kasahara, Akitsugu Sato, Hiromichi Yonekawa, Tsuyoshi Miyakawa, Jun Ichi Hayashi

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Mitochondrial DNA (mtDNA) with pathogenic mutations has been found in patients with cognitive disorders. However, little is known about whether pathogenic mtDNA mutations and the resultant mitochondrial respiration deficiencies contribute to the expression of cognitive alterations, such as impairments of learning and memory. To address this point, we used two groups of trans-mitochondrial mice (mito-mice) with heteroplasmy for wild-type and pathogenically deleted (Δ) mtDNA; the "low" group carried 50% or less ΔmtDNA, and the "high" group carried more than 50% ΔmtDNA. Results: Both groups had normal phenotypes for not only spatial learning, but also memory at short retention delays, indicating that ΔmtDNA load did not affect learning and temporal memory. The high group, however, showed severe impairment of memory at long retention delays. In the visual cortex and dentate gyrus of these mice, we observed mitochondrial respiration deficiencies, and reduced Ca2+/calmodulin-dependent kinase II-α (α-CaMKII), a protein important for the establishment of spatial remote memory. Conclusion: Our results indicated that normal mitochondrial respiratory function is necessary for retention and consolidation of memory trace; deficiencies in this function due to high loads of pathogenically mutated mtDNA are responsible for the preferential impairment of spatial remote memory.

Original languageEnglish
Article number21
JournalMolecular brain
Volume1
Issue number1
DOIs
Publication statusPublished - 01-01-2008

Fingerprint

Long-Term Memory
Mitochondrial DNA
Respiration
Learning
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Mutation
Dentate Gyrus
Visual Cortex
Spatial Memory
Phenotype
Retention (Psychology)

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Tanaka, D., Nakada, K., Takao, K., Ogasawara, E., Kasahara, A., Sato, A., ... Hayashi, J. I. (2008). Normal mitochondrial respiratory function is essential for spatial remote memory in mice. Molecular brain, 1(1), [21]. https://doi.org/10.1186/1756-6606-1-21
Tanaka, Daisuke ; Nakada, Kazuto ; Takao, Keizo ; Ogasawara, Emi ; Kasahara, Atsuko ; Sato, Akitsugu ; Yonekawa, Hiromichi ; Miyakawa, Tsuyoshi ; Hayashi, Jun Ichi. / Normal mitochondrial respiratory function is essential for spatial remote memory in mice. In: Molecular brain. 2008 ; Vol. 1, No. 1.
@article{75d77f18e436411b83bfbe423f46999a,
title = "Normal mitochondrial respiratory function is essential for spatial remote memory in mice",
abstract = "Background: Mitochondrial DNA (mtDNA) with pathogenic mutations has been found in patients with cognitive disorders. However, little is known about whether pathogenic mtDNA mutations and the resultant mitochondrial respiration deficiencies contribute to the expression of cognitive alterations, such as impairments of learning and memory. To address this point, we used two groups of trans-mitochondrial mice (mito-mice) with heteroplasmy for wild-type and pathogenically deleted (Δ) mtDNA; the {"}low{"} group carried 50{\%} or less ΔmtDNA, and the {"}high{"} group carried more than 50{\%} ΔmtDNA. Results: Both groups had normal phenotypes for not only spatial learning, but also memory at short retention delays, indicating that ΔmtDNA load did not affect learning and temporal memory. The high group, however, showed severe impairment of memory at long retention delays. In the visual cortex and dentate gyrus of these mice, we observed mitochondrial respiration deficiencies, and reduced Ca2+/calmodulin-dependent kinase II-α (α-CaMKII), a protein important for the establishment of spatial remote memory. Conclusion: Our results indicated that normal mitochondrial respiratory function is necessary for retention and consolidation of memory trace; deficiencies in this function due to high loads of pathogenically mutated mtDNA are responsible for the preferential impairment of spatial remote memory.",
author = "Daisuke Tanaka and Kazuto Nakada and Keizo Takao and Emi Ogasawara and Atsuko Kasahara and Akitsugu Sato and Hiromichi Yonekawa and Tsuyoshi Miyakawa and Hayashi, {Jun Ichi}",
year = "2008",
month = "1",
day = "1",
doi = "10.1186/1756-6606-1-21",
language = "English",
volume = "1",
journal = "Molecular Brain",
issn = "1756-6606",
publisher = "BioMed Central",
number = "1",

}

Tanaka, D, Nakada, K, Takao, K, Ogasawara, E, Kasahara, A, Sato, A, Yonekawa, H, Miyakawa, T & Hayashi, JI 2008, 'Normal mitochondrial respiratory function is essential for spatial remote memory in mice', Molecular brain, vol. 1, no. 1, 21. https://doi.org/10.1186/1756-6606-1-21

Normal mitochondrial respiratory function is essential for spatial remote memory in mice. / Tanaka, Daisuke; Nakada, Kazuto; Takao, Keizo; Ogasawara, Emi; Kasahara, Atsuko; Sato, Akitsugu; Yonekawa, Hiromichi; Miyakawa, Tsuyoshi; Hayashi, Jun Ichi.

In: Molecular brain, Vol. 1, No. 1, 21, 01.01.2008.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Normal mitochondrial respiratory function is essential for spatial remote memory in mice

AU - Tanaka, Daisuke

AU - Nakada, Kazuto

AU - Takao, Keizo

AU - Ogasawara, Emi

AU - Kasahara, Atsuko

AU - Sato, Akitsugu

AU - Yonekawa, Hiromichi

AU - Miyakawa, Tsuyoshi

AU - Hayashi, Jun Ichi

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Background: Mitochondrial DNA (mtDNA) with pathogenic mutations has been found in patients with cognitive disorders. However, little is known about whether pathogenic mtDNA mutations and the resultant mitochondrial respiration deficiencies contribute to the expression of cognitive alterations, such as impairments of learning and memory. To address this point, we used two groups of trans-mitochondrial mice (mito-mice) with heteroplasmy for wild-type and pathogenically deleted (Δ) mtDNA; the "low" group carried 50% or less ΔmtDNA, and the "high" group carried more than 50% ΔmtDNA. Results: Both groups had normal phenotypes for not only spatial learning, but also memory at short retention delays, indicating that ΔmtDNA load did not affect learning and temporal memory. The high group, however, showed severe impairment of memory at long retention delays. In the visual cortex and dentate gyrus of these mice, we observed mitochondrial respiration deficiencies, and reduced Ca2+/calmodulin-dependent kinase II-α (α-CaMKII), a protein important for the establishment of spatial remote memory. Conclusion: Our results indicated that normal mitochondrial respiratory function is necessary for retention and consolidation of memory trace; deficiencies in this function due to high loads of pathogenically mutated mtDNA are responsible for the preferential impairment of spatial remote memory.

AB - Background: Mitochondrial DNA (mtDNA) with pathogenic mutations has been found in patients with cognitive disorders. However, little is known about whether pathogenic mtDNA mutations and the resultant mitochondrial respiration deficiencies contribute to the expression of cognitive alterations, such as impairments of learning and memory. To address this point, we used two groups of trans-mitochondrial mice (mito-mice) with heteroplasmy for wild-type and pathogenically deleted (Δ) mtDNA; the "low" group carried 50% or less ΔmtDNA, and the "high" group carried more than 50% ΔmtDNA. Results: Both groups had normal phenotypes for not only spatial learning, but also memory at short retention delays, indicating that ΔmtDNA load did not affect learning and temporal memory. The high group, however, showed severe impairment of memory at long retention delays. In the visual cortex and dentate gyrus of these mice, we observed mitochondrial respiration deficiencies, and reduced Ca2+/calmodulin-dependent kinase II-α (α-CaMKII), a protein important for the establishment of spatial remote memory. Conclusion: Our results indicated that normal mitochondrial respiratory function is necessary for retention and consolidation of memory trace; deficiencies in this function due to high loads of pathogenically mutated mtDNA are responsible for the preferential impairment of spatial remote memory.

UR - http://www.scopus.com/inward/record.url?scp=68949129553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68949129553&partnerID=8YFLogxK

U2 - 10.1186/1756-6606-1-21

DO - 10.1186/1756-6606-1-21

M3 - Article

C2 - 19087269

AN - SCOPUS:68949129553

VL - 1

JO - Molecular Brain

JF - Molecular Brain

SN - 1756-6606

IS - 1

M1 - 21

ER -