Dataset Information

Microglial TREM2 Mitigates Inflammatory Responses and Neuronal Apoptosis in Angiotensin II-Induced Hypertension in Middle-Aged Mice.

ABSTRACT: Growing evidence suggests that hypertension and aging are prominent risk factors for the development of late-onset Alzheimer's disease (LOAD) by inducement of neuroinflammation. Recent study showed that neuroinflammation via activated microglia induces reactive astrocytes, termed A1 astrocytes, that highly upregulate numerous classical complement cascade genes that are destructive to neurons in neurodegeneration diseases. Moreover, triggering receptor expressed on myeloid cells 2 (TREM2) is considered as one of the strongest single-allele genetic risk factors and plays important roles in neuroinflammation for LOAD. However, the mechanisms of microglia in the regulation of A1 astrocytic activation are still not clear. We introduced angiotensin II-induced hypertension in middle-aged mice and found that hypertension-upregulated TREM2 expression and A1 astrocytic activation were involved in neuroinflammation in the animal models used in this study. The in vitro results revealed that overexpression of microglial TREM2 not only mitigated microglial inflammatory response but also had salutary effects on reverse A1 astrocytic activation and neuronal toxicity.

SUBMITTER: Xu X

PROVIDER: S-EPMC8417947 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Microglial TREM2 Mitigates Inflammatory Responses and Neuronal Apoptosis in Angiotensin II-Induced Hypertension in Middle-Aged Mice.

Xu Xiaotian X Du Lin L Jiang Jianxiong J Yang Ming M Wang Zhaoxia Z Wang Yingge Y Tang Tieyu T Fu Xuetao X Hao Jiukuan J

Frontiers in aging neuroscience 20210820

Growing evidence suggests that hypertension and aging are prominent risk factors for the development of late-onset Alzheimer's disease (LOAD) by inducement of neuroinflammation. Recent study showed that neuroinflammation <i>via</i> activated microglia induces reactive astrocytes, termed A1 astrocytes, that highly upregulate numerous classical complement cascade genes that are destructive to neurons in neurodegeneration diseases. Moreover, triggering receptor expressed on myeloid cells 2 (TREM2) ...[more]

PMID: 34489683

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Project description:RationaleIncreased microglial activation and neuroinflammation within autonomic brain regions have been implicated in sustained hypertension, and their inhibition by minocycline-an anti-inflammatory antibiotic-produces beneficial effects. These observations led us to propose a dysfunctional brain-gut communication hypothesis for hypertension. However, it has been difficult to reconcile whether an anti-inflammatory or antimicrobial action is the primary beneficial effect of minocycline in hypertension. Accordingly, we utilized chemically modified tetracycline-3 (CMT-3)-a derivative of tetracycline that has potent anti-inflammatory activity-to address this question.ObjectiveTest the hypothesis that central administration of CMT-3 would inhibit microglial activation, attenuate neuroinflammation, alter selective gut microbial communities, protect the gut wall from developing hypertension-associated pathology, and attenuate hypertension.Methods and resultsRats were implanted with radiotelemetry devices for recording mean arterial pressure. Ang II (angiotensin II) was infused subcutaneously using osmotic mini-pumps to induce hypertension. Another osmotic mini-pump was surgically implanted to infuse CMT-3 intracerebroventricularly. Intracerebroventricular CMT- 3 infusion was also investigated in SHR (spontaneously hypertensive rats). Physiological, pathological, immunohistological parameters, and fecal microbiota were analyzed. Intracerebroventricular CMT-3 significantly inhibited Ang II-induced increases in number of microglia, their activation, and proinflammatory cytokines in the paraventricular nucleus of hypothalamus. Further, intracerebroventricular CMT-3 attenuated increased mean arterial pressure, normalized sympathetic activity, and left ventricular hypertrophy in Ang II rats, as well as in the SHR. Finally, CMT-3 beneficially restored certain gut microbial communities altered by Ang II and attenuated pathological alterations in gut wall.ConclusionsThese observations demonstrate that inhibition of microglial activation alone was sufficient to induce significant antihypertensive effects. This was associated with unique changes in gut microbial communities and profound attenuation of gut pathology. They suggest, for the first time, a link between microglia and certain microbial communities that may have implications for treatment of hypertension.

Dataset Information

Microglial TREM2 Mitigates Inflammatory Responses and Neuronal Apoptosis in Angiotensin II-Induced Hypertension in Middle-Aged Mice.

Publications

Microglial TREM2 Mitigates Inflammatory Responses and Neuronal Apoptosis in Angiotensin II-Induced Hypertension in Middle-Aged Mice.

Similar Datasets

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