QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 1, 2009, 29(26):8363-8371; doi:10.1523/JNEUROSCI.3216-08.2009

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tanaka, H. Articles by Ikenaka, K. Search for Related Content PubMed PubMed Citation Articles by Tanaka, H. Articles by Ikenaka, K.

 Previous Article  |  Next Article 

Neurobiology of Disease
Mice with Altered Myelin Proteolipid Protein Gene Expression Display Cognitive Deficits Accompanied by Abnormal Neuron–Glia Interactions and Decreased Conduction Velocities

Hisataka Tanaka,^1 * Jianmei Ma,^1,5 * Kenji F. Tanaka,^1 * Keizo Takao,^6,7 Munekazu Komada,^2,10 Koichi Tanda,⁶ Ayaka Suzuki,⁸ Tomoko Ishibashi,⁸ Hiroko Baba,⁸ Tadashi Isa,³ Ryuichi Shigemoto,⁴ Katsuhiko Ono,⁹ Tsuyoshi Miyakawa,^2,6,7,10 and Kazuhiro Ikenaka^1,10

¹Division of Neurobiology and Bioinformatics, ²Center for Genetic Analysis of Behavior, ³Department of Developmental Physiology, and ⁴Division of Cerebral Structure, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan, ⁵Department of Anatomy, Dalian Medical University, Dalian, Liaoning 116044, China, ⁶Genetic Engineering and Functional Genomics Group, Horizontal Medical Research Organization, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606-8501, Japan, ⁷Division of Systems Medicine, Institute for Comprehensive Medical Science, Fujita Health University, Aichi 470-1192, Japan, ⁸Department of Molecular Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Japan, ⁹Department of Biology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan, and ¹⁰Japan Science and Technology Agency, Core Research for Evolutionary Science and Technology, Kawaguchi 332-0012, Japan

Correspondence should be addressed to Kazuhiro Ikenaka, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan. Email: ikenaka{at}nips.ac.jp

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 (plp1^tg/– mice) at 2 months of age. At this stage, the plp1^tg/– 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 plp1^tg/– 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.

---

Received July 9, 2008; revised May 8, 2009; accepted May 25, 2009.

Correspondence should be addressed to Kazuhiro Ikenaka, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan. Email: ikenaka{at}nips.ac.jp

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2009 29: i. [Full Text]  

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help