Apoptosis in oligodendrocytes is associated with axonal degeneration in P301L tau mice.
Transgenic mice overexpressing human tau with the P301L mutation develop neurofibrillary tangles, extensive gliosis, adult-onset motor abnormalities, and neuronal loss in affected brain regions. We investigated the mechanism of neuronal cell death in this model of tauopathy. There was no evidence of neuronal apoptosis at any age; however, a population of oligodendorocytes was immunopositive for TUNEL and activated caspase-3. EM confirmed that these oligodendrocytes were undergoing apoptosis. These data suggest that classical apoptosis is not a major mechanism of neuronal cell death associated with the tau dysfunction in this mouse model; however, prominent white matter pathology in the spinal cord suggests that axonal degeneration in dying neurons causes oligodendrocytes to undergo apoptosis. It is unknown if loss of oligodendrocytes either through apoptosis or through the formation of intracellular tau lesions further contributes to the neurodegeneration seen in these mice.
Zehr
Cindy
C
Neurogenetics Laboratory, Mayo Clinic, Jacksonville, FL 32224, USA.
Lewis
Jada
J
McGowan
Eileen
E
Crook
Julia
J
Lin
Wen-Lang
WL
Godwin
Kate
K
Knight
Joshua
J
Dickson
Dennis W
DW
Hutton
Mike
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009154:Mutation; D009410:Nerve Degeneration / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000473:pathology* / Q000648:ultrastructure; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000235:genetics*
C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; D016875:tau Proteins; C051774:neurofilament protein H; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases