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

Traumatic Brain Injury in Young Rats Leads to Progressive Behavioral Deficits Coincident with Altered Tissue Properties in Adulthood

“…The decreased CAP suggests that the increase of MBP observed in CCI animals is non-functional and insufficient to compensate for the loss of axons after CCI. Our findings are similar to a recent report in mice showing that myelin proteolipid protein (PLP) overexpression was associated with decreased axonal conductance velocity (Tanaka et al, 2009). Interestingly, Kodama and associates (2008) used the same mouse anti-MBP antibody, and found increased MBP protein levels in adulthood following early weaning.…”

The neurobiology of transition to psychosis

“…87,90,91 A number of myelin gene knockout mice models exhibit schizophrenia-like behaviours. [92][93][94] Consistent with this notion, using 7 T magnetization transfer imaging in conjunction with 3 T diffusion tensor imaging, we reported significant reduction in myelin affecting both white matter and cortical grey matter in the occipitotemporal cortex in a medicated group of patients with schizophrenia. 95 Interestingly, Dukart and colleagues and others who observed increased grey matter in individuals with psychosis 30,31,32 report increased grey matter in overlapping occipitotemporal regions.…”

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

“…We have obtained a large set of raw data of more than 1200 mice, and have reported the data for the T-maze performance in several strains of mutant mice 3,[16][17][18][19][20][21][22] . The data of strains already published in the research article are included in the "Mouse Behavioral Phenotype Database" as a public database (URL: http://www.mousephenotype.org/).…”