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Original Paper

Learning Deficits and Agenesis of Synapses and Myelinated Axons in Phosphoinositide-3 Kinase-Deficient Mice

Tohda C.a · Nakanishi R.a · Kadowaki M.b

Author affiliations

Divisions of a Biofunctional Evaluation, Research Center for Ethnomedicine and bGastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, Toyama, Japan

Corresponding Author

Chihiro Tohda, PhD

Division of Biofunctional Evaluation, Research Center for Ethnomedicine

Institute of Natural Medicine, University of Toyama

Toyama 930-0194 (Japan)

Tel. +81 76 434 7646, Fax +81 76 434 5068, E-Mail chihiro@inm.u-toyama.ac.jp

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Neurosignals 2006–07;15:293–306

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Abstract

Although previous studies have reported a role for phosphoinositide-3 kinase (PI3K) in axonal definition and growth in vitro, it is not clear whether PI3K regulates axonal formation and synaptogenesis in vivo. The goal of the present study was to clarify the role of PI3K in behavioral functions and some underlying neuroanatomical structures. Immunohistochemistry, an electron-microscopic analysis and behavioral tests were carried out. Knockout mice lacking the p85α regulatory subunit of PI3K (p85α–/– mice) significantly showed learning deficits, restlessness and motivation deficit. Expression of phosphorylated Akt, which indirectly shows the activity of PI3K, was high in myelinated axons, especially in axonal bundles in the striatum of wild-type mice, but was significantly low in the striatum, cerebral cortex and the hippocampal CA3 of p85α–/– mice. The axonal marker protein level decreased mainly in the striatum and cerebral cortex of p85α–/– mice. In these two regions, myelinated axons are rich in the wild-type mice. However, the density of myelinated axons and myelin thickness were significantly low in the striatum and cerebral cortex of p85α–/– mice. Synaptic protein level was clearly decreased in the striatum, cerebral cortex, and hippocampus of p85α–/– mice when compared with wild mice. The present results suggest that PI3K plays a role in the generation and/or maintenance of synapses and myelinated axons in the brain and that deficiencies in PI3K activity result in abnormalities in several neuronal functions, including learning, restlessness and motivation.

© 2007 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 27, 2007
Accepted: July 26, 2007
Published online: September 27, 2007
Issue release date: May 2008

Number of Print Pages: 14
Number of Figures: 7
Number of Tables: 0

ISSN: 1424-862X (Print)
eISSN: 1424-8638 (Online)

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