Comparison of myelin, axon, lipid, and immunopathology in the central nervous system of differentially myelin-compromised mutant mice: a morphological and biochemical study.

TY - JOUR

T1 - Comparison of myelin, axon, lipid, and immunopathology in the central nervous system of differentially myelin-compromised mutant mice: a morphological and biochemical study.

AU - Loers, Gabriele

AU - Aboul-Enein, Fahmy

AU - Bartsch, Udo

AU - Lassmann, Hans

AU - Schachner, Melitta

PY - 2004/10

Y1 - 2004/10

N2 - The present study was carried out to compare different myelin-compromised mouse mutants with regard to myelin morphology in relation to axon-, lipid-, and immunopathology as a function of age. Mouse mutants deficient in the myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) display subtle and severe myelin pathologies in the central nervous system (CNS), respectively. Animals doubly deficient in MAG and the neural cell adhesion molecule (NCAM) show defects similar to those present in MAG single mutants while mice deficient in MAG and the nonreceptor type tyrosine kinase Fyn are severely hypomyelinated, in addition to the MAG-specific myelin abnormalities. These mutant mice showed distinct myelin pathologies in different regions of the central nervous system and generally displayed a decrease in axonal integrity with age. Myelin pathology did not correlate locally with axon transection and with an involvement of the immune system as seen by numbers of CD3-positive lymphocytes and MAC-3-positive macrophages. Interestingly, the degree of these cellular abnormalities also did not correlate with abnormalities in levels of phospholipids, arachidonic acid, cholesterol, and apolipoprotein E (apoE). Moreover, these changes in lipid metabolism, including immune system-related arachidonic acid, preceded cellular pathology. The combined observations point to differences, but also similarities in the relation of myelin, axon, and immunopathology with genotype, and to a common aggravation of the phenotype with age.

AB - The present study was carried out to compare different myelin-compromised mouse mutants with regard to myelin morphology in relation to axon-, lipid-, and immunopathology as a function of age. Mouse mutants deficient in the myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) display subtle and severe myelin pathologies in the central nervous system (CNS), respectively. Animals doubly deficient in MAG and the neural cell adhesion molecule (NCAM) show defects similar to those present in MAG single mutants while mice deficient in MAG and the nonreceptor type tyrosine kinase Fyn are severely hypomyelinated, in addition to the MAG-specific myelin abnormalities. These mutant mice showed distinct myelin pathologies in different regions of the central nervous system and generally displayed a decrease in axonal integrity with age. Myelin pathology did not correlate locally with axon transection and with an involvement of the immune system as seen by numbers of CD3-positive lymphocytes and MAC-3-positive macrophages. Interestingly, the degree of these cellular abnormalities also did not correlate with abnormalities in levels of phospholipids, arachidonic acid, cholesterol, and apolipoprotein E (apoE). Moreover, these changes in lipid metabolism, including immune system-related arachidonic acid, preceded cellular pathology. The combined observations point to differences, but also similarities in the relation of myelin, axon, and immunopathology with genotype, and to a common aggravation of the phenotype with age.

KW - Aging

KW - Animals

KW - Axons

KW - Central Nervous System

KW - Lipids

KW - Mice

KW - Mice, Mutant Strains

KW - Myelin Sheath

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.mcn.2004.06.006

DO - 10.1016/j.mcn.2004.06.006

M3 - SCORING: Journal article

C2 - 15485773

VL - 27

SP - 175

EP - 189

JO - MOL CELL NEUROSCI

JF - MOL CELL NEUROSCI

SN - 1044-7431

IS - 2

M1 - 2

ER -