Type-Dependent Oxidative Damage Frontotemporal Lobar Degeneration: Cortical Astrocytes Are Targets of Oxidative Damage

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2008
Author
Martínez, Anna
Carmona, Margarita
Portero Otín, Manuel
Naudí i Farré, Alba
Pamplona Gras, Reinald
Ferrer, Isidre
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Martínez, Anna; Carmona, Margarita; Portero Otín, Manuel; Naudí i Farré, Alba; Pamplona Gras, Reinald; Ferrer, Isidre; . (2008) . Type-Dependent Oxidative Damage Frontotemporal Lobar Degeneration: Cortical Astrocytes Are Targets of Oxidative Damage. Journal of Neuropathology and Experimental Neurology, 2008, vol. 67, núm. 12, p. 1122-1136. https://doi.org/10.1097/NEN.0b013e31818e06f3.
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Abstract
Oxidative injury and stress responses are common features of many neurodegenerative diseases. To assess oxidative stress responses in frontotemporal lobar degeneration (FTLD), we identified increased 4-hydroxynonenal (HNE) adducts using gel electrophoresis and Western blotting in frontal cortex samples in 6 of 6 cases of FTLD with the P301L mutation in the tau gene (FTLD-tau), in 3 of 10 cases with tau-negative ubiquitin-immunoreactive inclusions, and in 2 of 3 cases associated with motor neuron disease. Selectively increased lipoxidation-derived protein damage associated with altered membrane unsaturation and fatty acid profiles was verified by mass spectrometry in FTLD-tau and FTLD associated with motor neuron disease. All FTLD-tau and most cases with increased HNEpositive bands had marked astrocytosis as determined by glial fibrillary acidic protein (GFAP) immunohistochemistry and increased GFAP expression on Western blotting; 2 FTLD cases with tau-negative ubiquitin-immunoreactive inclusions and with increased GFAP expression did not have increased HNE adducts. Bidimensional gel electrophoresis, Western blotting, in-gel digestion, and mass spectrometry identified GFAP as a major target of lipoxidation in all positive cases; confocal microscopy revealed colocalization of HNE and GFAP in cortical astrocytes, superoxide dismutase 1 in astrocytes, and superoxide dismutase 2 in astrocytes and neurons in all FTLD types. Thus, in FTLD, there is variable disease-dependent oxidative damage that is prominent in FTLD-tau, astrocytes are targets of oxidative damage, and GFAP is a target of lipoxidation. Astrocytes are, therefore, crucial elements of oxidative stress responses in FTLD.
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http://hdl.handle.net/10459.1/57165
DOI
https://doi.org/10.1097/NEN.0b013e31818e06f3
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Journal of Neuropathology and Experimental Neurology, 2008, vol. 67, núm. 12, p. 1122-1136
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