Activity-induced MEMRI cannot detect functional brain anomalies in the APPxPS1-Ki mouse model of Alzheimer's disease.
Sci Rep
; 9(1): 1140, 2019 02 04.
Article
em En
| MEDLINE
| ID: mdl-30718666
ABSTRACT
Alzheimer's disease (AD) is the most common cause of dementia. Aside neuropathological lesions, abnormal neuronal activity and brain metabolism are part of the core symptoms of the disease. Activity-induced Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) has been proposed as a powerful approach to visualize evoked brain activity in rodents. Here, we evaluated the relevance of MEMRI in measuring neuronal (dys-)function in the APPxPS1 knocked-in (KI) mouse model of AD. Brain anomalies were firstly demonstrated in APPxPS1-Ki mice using cognitive testing (memory impairment) and histological mapping of immediate early gene products (decreased density of fos-positive neurons). Paradoxically, MEMRI analyses were not able to confirm the occurrence of neuronal hypoactivities in vivo. We then performed a neuropathological analysis that highlighted an abnormal increased permeability of the blood-brain barrier (BBB) in APPxPS1-Ki mice. We hypothesized that diffuse weakening of the BBB results in an uncontrolled diffusion of the MR contrast agent and a lack of correlation between manganese accumulation and neuronal activity. These results bring to light a limitation of the activity-induced MEMRI approach when applied to the APPxPS1-Ki mouse model as well as other mouse models harboring a compromised BBB.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imageamento por Ressonância Magnética
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Barreira Hematoencefálica
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Doença de Alzheimer
Tipo de estudo:
Diagnostic_studies
/
Evaluation_studies
Limite:
Animals
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
França