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Establishment of Novel Murine Model showing Vascular Inflammation-derived Cognitive Dysfunction
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- Inflammation is a critical feature of aging and its related diseases, including cardiovascular diseases. Recent epidemiological studies demonstrated that abdominal aortic aneurysm (AAA), an aging-related vascular pathological condition, is associated with cognitive decline. However, the underlying mechanism, especially the role of vascular inflammation, is largely unknown because of lack of an available animal model. In this study, we examined whether vascular inflammation affects synaptic and cognitive dysfunction, using an AAA mouse model. In young (3 months) and middle-aged (12 months) C57BL/6J mice, AAA was induced by angiotensin II infusion with calcium chloride application. After 4 weeks of induction, aortic diameter was significantly increased and excessive Mac3-positive inflammatory cells infiltrated the destroyed aorta in middle-aged mice. AAA-induced middle-aged mice further exhibited cognitive impairment. Neuronal loss was observed in the CA3 region of the hippocampus. IBA1/MHCII-double-positive microglia activation was also seen in the hippocampus, suggesting that vascular inflammation drives neuroinflammation and subsequent cognitive dysfunction. Furthermore, we found that senescence-accelerated mice prone 8 exhibited robust AAA formation and a marked decrease of cognitive and synaptic function in the hippocampus mediated by inflammation. In conclusion, this novel murine model convincingly suggested the occurrence of vascular inflammation-derived cognitive dysfunction.
- Subjects :
- 0301 basic medicine
Male
Pathology
medicine.medical_specialty
Aging
Genes, MHC Class II
Hippocampus
lcsh:Medicine
Inflammation
Article
03 medical and health sciences
Aortic aneurysm
Calcium Chloride
Mice
0302 clinical medicine
medicine.artery
Medicine
Animals
Cognitive Dysfunction
Aorta, Abdominal
Cognitive decline
lcsh:Science
Neuroinflammation
Aorta
Multidisciplinary
Microglia
business.industry
Angiotensin II
Calcium-Binding Proteins
Microfilament Proteins
lcsh:R
Macrophage Activation
medicine.disease
Antigens, Differentiation
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
lcsh:Q
medicine.symptom
business
030217 neurology & neurosurgery
Aortic Aneurysm, Abdominal
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....282dd5a167b3d0ff1d252ebaf56f6758