Mice with altered myelin proteolipid protein gene expression display cognitive deficits accompanied by abnormal neuron-glia interactions and decreased conduction velocities.
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.
Tanaka
Hisataka
H
Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan.
Ma
Jianmei
J
Tanaka
Kenji F
KF
Takao
Keizo
K
Komada
Munekazu
M
Tanda
Koichi
K
Suzuki
Ayaka
A
Ishibashi
Tomoko
T
Baba
Hiroko
H
Isa
Tadashi
T
Shigemoto
Ryuichi
R
Ono
Katsuhiko
K
Miyakawa
Tsuyoshi
T
Ikenaka
Kazuhiro
K
D000223:Adaptation, Psychological / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation; D018737:Hand Strength / Q000502:physiology; D007266:Inhibition, Psychological; D051663:Kv1.2 Potassium Channel / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D009431:Neural Conduction / Q000235:genetics*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000473:pathology; D009483:Neuropsychological Tests; D017288:Pain Threshold / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D011901:Ranvier's Nodes / Q000473:pathology / Q000648:ultrastructure; D013216:Reflex, Startle / Q000235:genetics; D013550:Swimming / Q000502:physiology
D051663:Kv1.2 Potassium Channel; D018991:Myelin Proteolipid Protein; C047516:Plp1 protein, mouse