Dataset Information

TREM2 Overexpression Attenuates Cognitive Deficits in Experimental Models of Vascular Dementia.

ABSTRACT: Neuroinflammation plays a prominent role in the pathogenesis of vascular dementia (VD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor mainly expressed on microglia and has been known for its anti-inflammatory properties during immune response. However, data evaluating the effects of TREM2 in VD are lacking. Therefore, the present study is aimed at investigating the role of TREM2 in VD. In this study, the mouse model of VD was induced by transient bilateral common carotid artery occlusion (BCCAO). We compared the hippocampal gene and protein expressions of TREM2 between the VD mice and sham-operated mice at different time points. The TREM2 mRNA and protein expression levels in the VD mice were higher than those in the sham-operated mice. The cognitive deficits of VD mice were observed in the Morris water maze test. Interestingly, overexpression of TREM2 by intracerebroventricular injection of a lentiviral vector that encoded TREM2 (LV-TREM2) significantly improved the spatial learning and memory and attenuated the hippocampal neural loss in VD mice. Further mechanistic study revealed that overexpression of TREM2 significantly inhibited microglia M1 polarization by decreasing inducible nitric oxide synthase (iNOS) and proinflammatory cytokines expression levels and conversely enhanced microglia M2 polarization by increasing Arginase-1 (Arg-1) and anti-inflammatory cytokine expression levels. These results strongly suggest that TREM2 provides a protective effect in VD via modulating the phenotype of activated microglia and may serve as a novel potential therapeutic target for VD.

SUBMITTER: Wang Q

PROVIDER: S-EPMC7306072 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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TREM2 Overexpression Attenuates Cognitive Deficits in Experimental Models of Vascular Dementia.

Wang Qian Q Yang Weixia W Zhang Jingmei J Zhao Yueran Y Xu Yuzhen Y

Neural plasticity 20200612

Neuroinflammation plays a prominent role in the pathogenesis of vascular dementia (VD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor mainly expressed on microglia and has been known for its anti-inflammatory properties during immune response. However, data evaluating the effects of TREM2 in VD are lacking. Therefore, the present study is aimed at investigating the role of TREM2 in VD. In this study, the mouse model of VD was induced by transient bilateral ...[more]

PMID: 32617097

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Project description:Subcortical vascular mild cognitive impairment (svMCI) is the predementia stage of subcortical vascular dementia (SVaD). The aim of this research is to explore and compare cerebral gray matter (GM) volume reduction in svMCI patients and SVaD patients, and to investigate the relationship between cerebral GM volume reduction and cognitive deficits.Thirty one svMCI patients, 29 SVaD patients, and 31 healthy controls were recruited in our research. They conducted neuropsychological tests and brain structural magnetic resonance imaging (MRI) examination. To detect cerebral GM volume reduction in svMCI patients and SVaD patients, we used statistical parametric mapping 8-voxel-based morphometry 8 (SPM8-VBM8) method to analyze MRI data. To detect the relationship between cerebral GM volume reduction and cognitive deficits, multiple linear regression analysis was used.Compared with healthy controls, svMCI patients showed cerebral GM volume reduction in hippocampus and parahippocampal gyrus, insula and superior temporal gyrus. Compared with healthy controls, SVaD patients exhibited more atrophy which encompasses all of these areas plus anterior and middle cingulate, inferior temporal gyrus, orbitofrontal cortex, and superior frontal gyrus. In svMCI patients, cerebral GM volume reduction correlated with memory loss, attention dysfunction, and language dysfunction; in SVaD patients, besides those cognitive deficits, cerebral GM volume reduction correlated with more cognitive impairments, including executive dysfunction, neuropsychiatric symptom, and depression.Our findings prove that both svMCI patients and SVaD patients exhibit cerebral GM volume reduction and there may exist a hierarchy between svMCI and SVaD, and cerebral GM volume reduction in both svMCI patients and SVaD patients correlates with cognitive deficits, which can help us understand the mechanism of cognitive impairments in svMCI patients and SVaD patients, and diagnose SVaD at its early stage.

Dataset Information

TREM2 Overexpression Attenuates Cognitive Deficits in Experimental Models of Vascular Dementia.

Publications

TREM2 Overexpression Attenuates Cognitive Deficits in Experimental Models of Vascular Dementia.

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