Chronic copper exposure directs microglia towards degenerative expression signatures in wild-type and J20 mouse model of Alzheimer's disease.
J Trace Elem Med Biol
; 62: 126578, 2020 Dec.
Article
in En
| MEDLINE
| ID: mdl-32599538
ABSTRACT
BACKGROUND:
Copper (Cu) is an essential metal mediating a variety of vital biological reactions with its redox property. Its dyshomeostasis has been associated with accelerated cognitive decline and neurodegenerative disorders, such as Alzheimer's disease (AD). However, underlying neurotoxic mechanisms elicited by dysregulated Cu remain largely elusive. We and others previously demonstrated that exposure to Cu in drinking water significantly exacerbated pathological hallmarks of AD and pro-inflammatory activation of microglia, coupled with impaired phagocytic capacity, in mouse models of AD.METHODS:
In the present study, we extended our investigation to evaluate whether chronic Cu exposure to wild-type (WT) and J20 mouse model of AD perturbs homeostatic dynamics of microglia and contributes to accelerated transformation of microglia towards degenerative phenotypes that are closely associated with neurodegeneration. We further looked for evidence of alterations in the microglial morphology and spatial memory of the Cu-exposed mice to assess the extent of the Cu toxicity.RESULTS:
We find that chronic Cu exposure to pre-pathological J20 mice upregulates the translation of degenerative genes and represses homeostatic genes within microglia even in the absence amyloid-beta plaques. We also observe similar expression signatures in Cu-exposed WT mice, suggesting that excess Cu exposure alone could lead to perturbed microglial homeostatic phenotypes and contribute to accelerated cognitive decline.CONCLUSION:
Our findings highlight the risk of chronic Cu exposure on cognitive decline and altered microglia activation towards degenerative phenotypes. These changes may represent one of the key mechanisms linking Cu exposure or its dyshomeostasis to an increased risk for AD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cognition Disorders
/
Microglia
/
Copper
/
Alzheimer Disease
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Trace Elem Med Biol
Journal subject:
METABOLISMO
/
SAUDE AMBIENTAL
Year:
2020
Document type:
Article
Affiliation country:
United States