Type-Dependent Oxidative Damage Frontotemporal Lobar Degeneration: Cortical Astrocytes Are Targets of Oxidative Damage
Issue date
2008Author
Martínez, Anna
Carmona, Margarita
Ferrer, Isidre
Suggested citation
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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Show full item recordAbstract
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.