Co-expression patterns of microglia markers Iba1, TMEM119 and P2RY12 in Alzheimer's disease

Kenkhuis, Boyd; Somarakis, Antonios; Kleindouwel, Lynn R.T.; Roon‐Mom, Willeke M. C. van; Höllt, Thomas; Weerd, Louise van der

doi:10.1016/j.nbd.2022.105684

Cited by 78 publications

(40 citation statements)

References 32 publications

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“…This suggests that TMEM119 protein is likely still involved in the activation of microglia, although the process of its downregulation in reactive microglia remains unclear. The present data in TBI ( Mercurio et al, 2022 ) are in agreement with the findings in the brain of patients with Alzheimer’s disease, in which the TMEM119 immunoreactivity is greatly reduced in the amyloid plaque-surrounding microglia and is often associated with a significant increase in Iba1 reactivity ( Swanson et al, 2020 ; Kenkhuis et al, 2022 ; Vankriekelsvenne et al, 2022 ). Moreover, the downregulation of TMEM119 protein in the contused area is in line with the findings at the sites of neurodegeneration where TMEM119 immunoreactivity is reduced in the disease-associated microglia ( Krasemann et al, 2017 ; Deczkowska et al, 2018 ; Satoh et al, 2019 ).…”

supporting

confidence: 91%

“…This finding is consistent with all the current findings so far regarding the protein expression of TMEM119 in the reactive microglia ( Satoh et al, 2019 ; Van Wageningen et al, 2019 ; Cao et al, 2021 ; Marzan et al, 2021 ; Young et al, 2021 ). However, it is rare to see a complete loss of TMEM119 immunoreactivity in Iba1-positive myeloid cells ( Li et al, 2019 ; Young et al, 2021 ), and only a proportion not all of the reactive microglia showed lower expression of TMEM119 ( Kenkhuis et al, 2022 ). This suggests that TMEM119 protein is likely still involved in the activation of microglia, although the process of its downregulation in reactive microglia remains unclear.…”

mentioning

confidence: 99%

“…Moreover, the downregulation of TMEM119 protein in the contused area is in line with the findings at the sites of neurodegeneration where TMEM119 immunoreactivity is reduced in the disease-associated microglia ( Krasemann et al, 2017 ; Deczkowska et al, 2018 ; Satoh et al, 2019 ). In these microglia, the expression of TMEM119 is not only reduced but is also redistributed to the phagosomes and/or the processes ( Young et al, 2021 ; Kenkhuis et al, 2022 ), suggesting that plasma membrane TMEM119 may be involved in the phagocytic function of microglia, such as apoptotic cells, cell debris or abnormal protein aggregates (i.e., amyloid plaques in Alzheimer’s). It is known that, during phagocytosis, the plasma membrane is embedded to form phagosomes that are transported to fuse with acidic lysosomes for non-specific degradation ( Underhill and Goodridge, 2012 ).…”

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confidence: 99%

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A New Understanding of TMEM119 as a Marker of Microglia

Ruan

Elyaman

2022

Front. Cell. Neurosci.

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confidence: 91%

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confidence: 99%

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confidence: 99%

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A New Understanding of TMEM119 as a Marker of Microglia

Ruan

Elyaman

2022

Front. Cell. Neurosci.

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“…Chymase, a serine protease in mast cells, were also increased in the HDM group compared to the intranasal PBS control group. To further explore the role of other immune cells that are potentially activated during allergic lung inflammation and can play a role in brain inflammation, we measured expression of Iba-1 protein, a microglial marker whose expression is generally higher in activated microglia [ 53 ]. Microglia are a type of macrophage in the brain whose increase in number is associated with brain inflammation.…”

Section: Discussionmentioning

confidence: 99%

Chronic allergic lung inflammation negatively influences neurobehavioral outcomes in mice

Kanaya

Yang

Emala

et al. 2022

J Neuroinflammation

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Background Asthma is a major public health problem worldwide. Emerging data from epidemiological studies show that allergies and allergic diseases may be linked to anxiety, depression and cognitive decline. However, little is known about the effect of asthma, an allergic lung inflammation, on cognitive decline/behavioral changes. Therefore, we investigated the hypothesis that allergic lung inflammation causes inflammation in the brain and leads to neurobehavioral changes in mice. Methods Wild-type C57BL/6J female mice were sensitized with nasal house dust mite (HDM) antigen or control PBS for 6 weeks to induce chronic allergic lung inflammation. A series of neurocognitive tests for anxiety and/or depression were performed before and after the intranasal HDM administration. After the behavior tests, tissues were harvested to measure inflammation in the lungs and the brains. Results HDM-treated mice exhibited significantly increased immobility times during tail suspension tests and significantly decreased sucrose preference compared with PBS controls, suggesting a more depressed and anhedonia phenotype. Spatial memory impairment was also observed in HDM-treated mice when assessed by the Y-maze novel arm tests. Development of lung inflammation after 6 weeks of HDM administration was confirmed by histology, bronchoalveolar lavage (BAL) cell count and lung cytokine measurements. Serum pro-inflammatory cytokines and Th2-related cytokines levels were elevated in HDM-sensitized mice. In the brain, the chemokine fractalkine was increased in the HDM group. The c-Fos protein, a marker for neuronal activity, Glial Fibrillary Acidic Protein (GFAP) and chymase, a serine protease from mast cells, were increased in the brains from mice in HDM group. Chymase expression in the brain was negatively correlated with the results of sucrose preference rate in individual mice. Conclusions 6 weeks of intranasal HDM administration in mice to mimic the chronic status of lung inflammation in asthma, caused significant inflammatory histological changes in the lungs, and several behavioral changes consistent with depression and altered spatial memory. Chymase and c-Fos proteins were increased in the brain from HDM-treated mice, suggesting links between lung inflammation and brain mast cell activation, which could be responsible for depression-like behavior.

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“…Iba-1, a marker of activation microglia, was widely used to identify immunopositivity microglia in a number of central nervous system disorders, such as Alzheimer's disease [ 51 ], schizophrenia and bipolar disorder [ 52 , 53 ], and spinal cord injury [ 54 , 55 ]. Not only did we confirm that Iba-1 was significantly expressed in SAMP8 mice but we also discovered that the expression of Iba-1 in the hippocampus and frontal lobe was proven to be positively connected to the blood levels of IL-6 and IL-1 β .…”

Section: Discussionmentioning

confidence: 99%

Effects of Electroacupuncture on the Correlation between Serum and Central Immunity in AD Model Animals

Jiang

Wang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. The goal was to investigate the connection between neuroinflammation in the brain and serum inflammatory markers as Alzheimer’s disease progressed. We also sought to determine whether electroacupuncture had an effect on inflammatory markers found in blood and other brain regions. Methods. As an animal model for AD, we used senescence-accelerated mouse prone 8 (SAMP8) mice. To examine the effects and probable mechanism of electroacupuncture, we used HE staining, immunofluorescence staining, western blotting, and enzyme-linked immunosorbent assay. Results. Electroacupuncture therapy protected neurons, significantly downregulated the Iba-1 level in the hippocampus ( p value was 0.003), frontal lobe cortex ( p value was 0.042), and temporal lobe cortex ( p value was 0.013) of the AD animal model, all of which had significantly lower levels of IL-6 ( p value was 0.001), IL-1β ( p value was 0.001), and TNF-α ( p value was 0.001) in their serum. Conclusion. The amounts of IL-6, IL-1β, and TNF-α detected in the serum were strongly linked to the levels discovered in the hippocampus and the frontal lobes of the brain, respectively. A better understanding of the electroacupuncture process as well as the course of Alzheimer’s disease and the therapeutic benefits of electroacupuncture may be gained by using biomarkers such as serum inflammatory marker biomarkers.

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Co-expression patterns of microglia markers Iba1, TMEM119 and P2RY12 in Alzheimer's disease

Cited by 78 publications

References 32 publications

A New Understanding of TMEM119 as a Marker of Microglia

A New Understanding of TMEM119 as a Marker of Microglia

Chronic allergic lung inflammation negatively influences neurobehavioral outcomes in mice

Effects of Electroacupuncture on the Correlation between Serum and Central Immunity in AD Model Animals

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