Mice with altered myelin proteolipid protein gene expression display cognitive deficits accompanied by abnormal neuron-glia interactions and decreased conduction velocities

Hisataka Tanaka, Jianmei Ma, Kenji F. Tanaka, Keizo Takao, Munekazu Komada, Koichi Tanda, Ayaka Suzuki, Tomoko Ishibashi, Hiroko Baba, Tadashi Isa, Ryuichi Shigemoto, Katsuhiko Ono, Tsuyoshi Miyakawa, Kazuhiro Ikenaka

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Conduction velocity (CV) of myelinated axons has been shown to be regulated by oligodendrocytes even after myelination has been completed. However, how myelinating oligodendrocytes regulate CV, and what the significance of this regulation is for normal brain function remain unknown. To address these questions, we analyzed a transgenic mouse line harboring extra copies of the myelin proteolipid protein 1 (plp1) gene (plp1tg/- mice) at 2 months of age. At this stage, the plp1tg/- mice have an unaffected myelin structure with a normally appearing ion channel distribution, but the CV in all axonal tracts tested in the CNS is greatly reduced. We also found decreased axonal diameters and slightly abnormal paranodal structures, both of which can be a cause for the reduced CV. Interestingly the plp1tg/- mice showed altered anxiety-like behaviors, reduced prepulse inhibitions, spatial learning deficits and working memory deficit, all of which are schizophrenia-related behaviors. Our results implicate that abnormalities in the neuron-glia interactions at the paranodal junctions can result in reduced CV in the CNS, which then induces behavioral abnormalities related to schizophrenia.

Original languageEnglish
Pages (from-to)8363-8371
Number of pages9
JournalJournal of Neuroscience
Volume29
Issue number26
DOIs
Publication statusPublished - 01-07-2009

Fingerprint

Myelin Proteolipid Protein
Neuroglia
Oligodendroglia
Gene Expression
Neurons
Schizophrenia
Memory Disorders
Myelin Sheath
Ion Channels
Short-Term Memory
Transgenic Mice
Axons
Anxiety
Brain
Genes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Tanaka, Hisataka ; Ma, Jianmei ; Tanaka, Kenji F. ; Takao, Keizo ; Komada, Munekazu ; Tanda, Koichi ; Suzuki, Ayaka ; Ishibashi, Tomoko ; Baba, Hiroko ; Isa, Tadashi ; Shigemoto, Ryuichi ; Ono, Katsuhiko ; Miyakawa, Tsuyoshi ; Ikenaka, Kazuhiro. / Mice with altered myelin proteolipid protein gene expression display cognitive deficits accompanied by abnormal neuron-glia interactions and decreased conduction velocities. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 26. pp. 8363-8371.
@article{2ff6e16c64a94bb48c4d52491fb53611,
title = "Mice with altered myelin proteolipid protein gene expression display cognitive deficits accompanied by abnormal neuron-glia interactions and decreased conduction velocities",
abstract = "Conduction velocity (CV) of myelinated axons has been shown to be regulated by oligodendrocytes even after myelination has been completed. However, how myelinating oligodendrocytes regulate CV, and what the significance of this regulation is for normal brain function remain unknown. To address these questions, we analyzed a transgenic mouse line harboring extra copies of the myelin proteolipid protein 1 (plp1) gene (plp1tg/- mice) at 2 months of age. At this stage, the plp1tg/- mice have an unaffected myelin structure with a normally appearing ion channel distribution, but the CV in all axonal tracts tested in the CNS is greatly reduced. We also found decreased axonal diameters and slightly abnormal paranodal structures, both of which can be a cause for the reduced CV. Interestingly the plp1tg/- mice showed altered anxiety-like behaviors, reduced prepulse inhibitions, spatial learning deficits and working memory deficit, all of which are schizophrenia-related behaviors. Our results implicate that abnormalities in the neuron-glia interactions at the paranodal junctions can result in reduced CV in the CNS, which then induces behavioral abnormalities related to schizophrenia.",
author = "Hisataka Tanaka and Jianmei Ma and Tanaka, {Kenji F.} and Keizo Takao and Munekazu Komada and Koichi Tanda and Ayaka Suzuki and Tomoko Ishibashi and Hiroko Baba and Tadashi Isa and Ryuichi Shigemoto and Katsuhiko Ono and Tsuyoshi Miyakawa and Kazuhiro Ikenaka",
year = "2009",
month = "7",
day = "1",
doi = "10.1523/JNEUROSCI.3216-08.2009",
language = "English",
volume = "29",
pages = "8363--8371",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "26",

}

Tanaka, H, Ma, J, Tanaka, KF, Takao, K, Komada, M, Tanda, K, Suzuki, A, Ishibashi, T, Baba, H, Isa, T, Shigemoto, R, Ono, K, Miyakawa, T & Ikenaka, K 2009, 'Mice with altered myelin proteolipid protein gene expression display cognitive deficits accompanied by abnormal neuron-glia interactions and decreased conduction velocities', Journal of Neuroscience, vol. 29, no. 26, pp. 8363-8371. https://doi.org/10.1523/JNEUROSCI.3216-08.2009

Mice with altered myelin proteolipid protein gene expression display cognitive deficits accompanied by abnormal neuron-glia interactions and decreased conduction velocities. / Tanaka, Hisataka; Ma, Jianmei; Tanaka, Kenji F.; Takao, Keizo; Komada, Munekazu; Tanda, Koichi; Suzuki, Ayaka; Ishibashi, Tomoko; Baba, Hiroko; Isa, Tadashi; Shigemoto, Ryuichi; Ono, Katsuhiko; Miyakawa, Tsuyoshi; Ikenaka, Kazuhiro.

In: Journal of Neuroscience, Vol. 29, No. 26, 01.07.2009, p. 8363-8371.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mice with altered myelin proteolipid protein gene expression display cognitive deficits accompanied by abnormal neuron-glia interactions and decreased conduction velocities

AU - Tanaka, Hisataka

AU - Ma, Jianmei

AU - Tanaka, Kenji F.

AU - Takao, Keizo

AU - Komada, Munekazu

AU - Tanda, Koichi

AU - Suzuki, Ayaka

AU - Ishibashi, Tomoko

AU - Baba, Hiroko

AU - Isa, Tadashi

AU - Shigemoto, Ryuichi

AU - Ono, Katsuhiko

AU - Miyakawa, Tsuyoshi

AU - Ikenaka, Kazuhiro

PY - 2009/7/1

Y1 - 2009/7/1

N2 - Conduction velocity (CV) of myelinated axons has been shown to be regulated by oligodendrocytes even after myelination has been completed. However, how myelinating oligodendrocytes regulate CV, and what the significance of this regulation is for normal brain function remain unknown. To address these questions, we analyzed a transgenic mouse line harboring extra copies of the myelin proteolipid protein 1 (plp1) gene (plp1tg/- mice) at 2 months of age. At this stage, the plp1tg/- mice have an unaffected myelin structure with a normally appearing ion channel distribution, but the CV in all axonal tracts tested in the CNS is greatly reduced. We also found decreased axonal diameters and slightly abnormal paranodal structures, both of which can be a cause for the reduced CV. Interestingly the plp1tg/- mice showed altered anxiety-like behaviors, reduced prepulse inhibitions, spatial learning deficits and working memory deficit, all of which are schizophrenia-related behaviors. Our results implicate that abnormalities in the neuron-glia interactions at the paranodal junctions can result in reduced CV in the CNS, which then induces behavioral abnormalities related to schizophrenia.

AB - Conduction velocity (CV) of myelinated axons has been shown to be regulated by oligodendrocytes even after myelination has been completed. However, how myelinating oligodendrocytes regulate CV, and what the significance of this regulation is for normal brain function remain unknown. To address these questions, we analyzed a transgenic mouse line harboring extra copies of the myelin proteolipid protein 1 (plp1) gene (plp1tg/- mice) at 2 months of age. At this stage, the plp1tg/- mice have an unaffected myelin structure with a normally appearing ion channel distribution, but the CV in all axonal tracts tested in the CNS is greatly reduced. We also found decreased axonal diameters and slightly abnormal paranodal structures, both of which can be a cause for the reduced CV. Interestingly the plp1tg/- mice showed altered anxiety-like behaviors, reduced prepulse inhibitions, spatial learning deficits and working memory deficit, all of which are schizophrenia-related behaviors. Our results implicate that abnormalities in the neuron-glia interactions at the paranodal junctions can result in reduced CV in the CNS, which then induces behavioral abnormalities related to schizophrenia.

UR - http://www.scopus.com/inward/record.url?scp=67649949466&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649949466&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.3216-08.2009

DO - 10.1523/JNEUROSCI.3216-08.2009

M3 - Article

C2 - 19571127

AN - SCOPUS:67649949466

VL - 29

SP - 8363

EP - 8371

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 26

ER -