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Mice with Altered Myelin Proteolipid Protein Gene Expression Display Cognitive Deficits Accompanied by Abnormal Neuron–Glia Interactions and Decreased Conduction Velocities
- Publication Year :
- 2009
- Publisher :
- Society for Neuroscience, 2009.
-
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 (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.
- Subjects :
- Genetically modified mouse
Central Nervous System
Pain Threshold
Reflex, Startle
Transgene
Neural Conduction
Mice, Inbred Strains
Mice, Transgenic
Biology
Neuropsychological Tests
Nerve Fibers, Myelinated
Nerve conduction velocity
Myelin
Mice
Microscopy, Electron, Transmission
Adaptation, Psychological
Ranvier's Nodes
medicine
Kv1.2 Potassium Channel
Animals
Maze Learning
Myelin Proteolipid Protein
Prepulse inhibition
Swimming
Regulation of gene expression
Neurons
Analysis of Variance
Hand Strength
General Neuroscience
Articles
Axons
Cell biology
Myelin proteolipid protein
Inhibition, Psychological
medicine.anatomical_structure
nervous system
Gene Expression Regulation
Exploratory Behavior
Neuron
Cognition Disorders
Neuroscience
Neuroglia
Psychomotor Performance
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....57209ab8005147315372ea2120894dfa