Knockdown of astrocytic TREM2 in the hippocampus relieves cognitive decline in elderly male mice

Wei, Mei-Dan; Lan, Yan-Xian; Lu, Kun Ping; Wang, Yan; Chen, Wenying

doi:10.1016/j.bbr.2020.112939

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…It is noteworthy that ameliorated cognitive decline has been reported in aging mice with astrocyte-selective downregulation of TREM2, which seemingly contradicts the beneficial effects of TREM2 stimulation in astrocytes reported earlier [29]. Even though further studies are needed to fully characterize the effects of TREM2 activation on astrocyte immune functions, this receptor could be considered for development of neuroprotective treatments.…”

Section: Triggering Receptor Expressed On Myeloid Cells 2 (Trem2)mentioning

confidence: 84%

Targeting neuroprotective functions of astrocytes in neuroimmune diseases

Klegeris

2021

Expert Opinion on Therapeutic Targets

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Section: Triggering Receptor Expressed On Myeloid Cells 2 (Trem2)mentioning

confidence: 84%

Targeting neuroprotective functions of astrocytes in neuroimmune diseases

Klegeris

2021

Expert Opinion on Therapeutic Targets

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“…Conversely, the hippocampal overexpression of TREM2 attenuated microglial activation and cognitive impairment in mice fed with HFD for 50 weeks [ 37 ]. In contrast to the microglial effect, decreased astrocytic TREM2 levels have demonstrated beneficial effects on learning and memory in aged mice [ 38 ]. The overexpression of TREM2 using an adeno-associated viral vector markedly reduced the activation of the NF-κB pathway and the associated neuroinflammatory response, affecting the levels of interleukin-1β, TNF-α, TLR4, and inducible nitric oxide synthase in the hippocampus of HFD-fed mice [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the microglial effect, decreased astrocytic TREM2 levels have demonstrated beneficial effects on learning and memory in aged mice [ 38 ]. The overexpression of TREM2 using an adeno-associated viral vector markedly reduced the activation of the NF-κB pathway and the associated neuroinflammatory response, affecting the levels of interleukin-1β, TNF-α, TLR4, and inducible nitric oxide synthase in the hippocampus of HFD-fed mice [ 38 ]. Thus, our study elucidated the idea that macrophage-derived TREM2 may be involved in the inflammatory response in the diabetic brain.…”

Section: Discussionmentioning

confidence: 99%

Lipocalin-2 Deficiency Reduces Hepatic and Hippocampal Triggering Receptor Expressed on Myeloid Cells-2 Expressions in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

Shin

Jin

et al. 2022

Brain Sciences

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Background: Lipocalin-2 (LCN2) is an acute-phase protein that has been linked to insulin resistance, diabetes, and neuroinflammatory diseases. Triggering receptor expressed on myeloid cells-2 (TREM2) has been also implicated in microglia-mediated neuroinflammation. However, the potential role of LCN2 on TREM2 in diabetic mouse models is not fully understood. Methods: We investigated hepatic and hippocampal TREM2 expressions in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic LCN2 knockout (KO) mice. Results: In addition to increased serum LCN2 level, diabetic wild-type (WT) mice had insulin resistance and hepatic steatosis. However, LCN2 deletion attenuated these metabolic parameters in diabetic mice. We also found that LCN2 deletion reduced hepatic inflammation and microglial activation in diabetic mice. In particular, diabetic LCN2 KO mice had a reduction in hepatic and hippocampal TREM2 expressions compared with diabetic WT mice. Furthermore, we found that many TREM2-positive Kupffer cells and microglia in diabetic WT mice were reduced through LCN2 deletion. Conclusions: These findings indicate that LCN2 may promote hepatic inflammation and microglial activation via upregulation of TREM2 in diabetic mice.

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TREM2 and CD163 Ameliorate Microglia-Mediated Inflammatory Environment in the Aging Brain

Han

Liu

et al. 2022

J Mol Neurosci

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Aging declines cognitive functions, especially learning and memory. Microglia-mediated neuroin ammation occurs in age-related neurodegenerative diseases. Our study obtained the expression pro le of GSE11882 from the Gene Expression Omnibus database and used microarray data to explore the expression of age-related genes in the hippocampus. A total of 120 differentially expressed genes (DEGs) were screened out and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed. In Cytoscape software, 18 key genes were identi ed by the plugin cytoHubba. Two genes with positive impact on cognition during aging were teased out, including triggering receptor expressed on myeloid cells 2 (TREM2) and scavenger receptor (CD163). Finally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) veri ed that the mRNA expression of two genes was signi cantly up-regulated in the Aged group. Moreover, the in ammatory factor IL-1β and IL-6 signi cantly increased. The up-regulation of TREM2 and CD163 may exert a compensatory effect on neurodegeneration by mitigating the in ammatory environment in the aging brain.

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Knockdown of astrocytic TREM2 in the hippocampus relieves cognitive decline in elderly male mice

Cited by 3 publications

References 41 publications

Targeting neuroprotective functions of astrocytes in neuroimmune diseases

Targeting neuroprotective functions of astrocytes in neuroimmune diseases

Lipocalin-2 Deficiency Reduces Hepatic and Hippocampal Triggering Receptor Expressed on Myeloid Cells-2 Expressions in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

TREM2 and CD163 Ameliorate Microglia-Mediated Inflammatory Environment in the Aging Brain

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