Agent Orange Herbicidal Toxin-Initiation of Alzheimer-Type Neurodegeneration.
J Alzheimers Dis
; 97(4): 1703-1726, 2024.
Article
em En
| MEDLINE
| ID: mdl-38306038
ABSTRACT
Background:
Agent Orange (AO) is a Vietnam War-era herbicide that contains a 1ââ1 ratio of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Emerging evidence suggests that AO exposures cause toxic and degenerative pathologies that may increase the risk for Alzheimer's disease (AD).Objective:
This study investigates the effects of the two main AO constituents on key molecular and biochemical indices of AD-type neurodegeneration.Methods:
Long Evans rat frontal lobe slice cultures treated with 250µg/ml of 2,4-D, 2,4,5-T, or both (Dâ+âT) were evaluated for cytotoxicity, oxidative injury, mitochondrial function, and AD biomarker expression.Results:
Treatment with the AO constituents caused histopathological changes corresponding to neuronal, white matter, and endothelial cell degeneration, and molecular/biochemical abnormalities indicative of cytotoxic injury, lipid peroxidation, DNA damage, and increased immunoreactivity to activated Caspase 3, glial fibrillary acidic protein, ubiquitin, tau, paired-helical filament phosphorylated tau, AßPP, Aß, and choline acetyltransferase. Nearly all indices of cellular injury and degeneration were more pronounced in the Dâ+âT compared with 2,4-D or 2,4,5-T treated cultures.Conclusions:
Exposures to AO herbicidal chemicals damage frontal lobe brain tissue with molecular and biochemical abnormalities that mimic pathologies associated with early-stage AD-type neurodegeneration. Additional research is needed to evaluate the long-term effects of AO exposures in relation to aging and progressive neurodegeneration in Vietnam War Veterans.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
/
Herbicidas
Limite:
Animals
Idioma:
En
Revista:
J Alzheimers Dis
Assunto da revista:
GERIATRIA
/
NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos