Caspase-dependent apoptosis induces reactivation and gliogenesis of astrocytes in adult mice

Kim, Seung-Chan; Park, Jae Yong; Hwang, Eun Mi

doi:10.3389/fncel.2022.1054956

Cited by 2 publications

(1 citation statement)

References 38 publications

(50 reference statements)

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“…Interestingly, our results showed that the intensity of GFAP fluorescent decreased in the young unvaccinated infected groups, possibly due to the infection of astrocytes by neurotropic influenza viruses, which has been previously reported to lead to apoptosis ( Pei et al, 2014 ; Ng et al, 2018 ; Hosseini and Korte, 2023 ). In this context, it has also been shown that apoptosis of astrocytes in the hippocampus with activated caspase-3 leads to a sharp decrease in astrocyte number ( Kim et al, 2022 ). Moreover, this evidence is consistent with previous findings that GFAP was downregulated during acute corneal HSV-1 infection and upregulated in the late stage, suggesting that GFAP may play some role during corneal HSV-1 infection ( Zhao et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Influenza vaccine is able to prevent neuroinflammation triggered by H7N7 IAV infection

et al. 2023

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Influenza A virus (IAV) subtypes are a major cause of illness and mortality worldwide and pose a threat to human health. Although IAV infection is considered a self-limiting respiratory syndrome, an expanded spectrum of cerebral manifestations has been reported following IAV infection. Neurotropic IAVs, such as the H7N7 subtype, are capable of invading the central nervous system (CNS) and replicating in brain cells, resulting in microglia-induced neuroinflammation. Microglial cells, the brain’s resident immune cells, are instrumental in the inflammatory response to viral infection. While activation of microglia is important to initially contain the virus, excessive activation of these cells leads to neuronal damage. Previous studies have shown that acute and even long-term IAV-induced neuroinflammation leads to CNS damage. Therefore, the search for possible preventive or therapeutic strategies is of great importance. In this study, we investigated the potential effect of vaccination against acute neuroinflammation induced by H7N7 infection and subsequent neuronal damage in the hippocampus, a particularly vulnerable brain region, comparing young and aged mice. Immunosenescence is one of the striking pathophysiological changes during mammalian aging that leads to “inflammaging” and critically limits the protection by vaccines in the elderly. The results suggest that formalin-inactivated H7N7 vaccine has a preventive effect against the inflammatory responses in the periphery and also in the CNS after H7N7 infection. Cytokine and chemokine levels, increased microglial density, and cell volume after H7N7 infection were all attenuated by vaccination. Further structural analysis of microglial cells also revealed a change in branching complexity after H7N7 infection, most likely reflecting the neuroprotective effect of the vaccination. In addition, synapse loss was prevented in vaccinated mice. Remarkably, engulfment of post-synaptic compartments by microglia can be proposed as the underlying mechanism for spine loss triggered by H7N7 infection, which was partially modulated by vaccination. Although young mice showed better protection against neuroinflammation and the resulting deleterious neuronal effects upon vaccination, a beneficial role of the vaccine was also observed in the brains of older mice. Therefore, vaccination can be proposed as an important strategy to prevent neurological sequelae of H7N7 infection.

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Section: Discussionmentioning

confidence: 99%

Influenza vaccine is able to prevent neuroinflammation triggered by H7N7 IAV infection

et al. 2023

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Astrocytic autophagy plasticity modulates Aβ clearance and cognitive function in Alzheimer’s disease

Kim,

Chun,

Kim

et al. 2024

Mol Neurodegeneration

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Background Astrocytes, one of the most resilient cells in the brain, transform into reactive astrocytes in response to toxic proteins such as amyloid beta (Aβ) in Alzheimer’s disease (AD). However, reactive astrocyte-mediated non-cell autonomous neuropathological mechanism is not fully understood yet. We aimed our study to find out whether Aβ-induced proteotoxic stress affects the expression of autophagy genes and the modulation of autophagic flux in astrocytes, and if yes, how Aβ-induced autophagy-associated genes are involved Aβ clearance in astrocytes of animal model of AD. Methods Whole RNA sequencing (RNA-seq) was performed to detect gene expression patterns in Aβ-treated human astrocytes in a time-dependent manner. To verify the role of astrocytic autophagy in an AD mouse model, we developed AAVs expressing shRNAs for MAP1LC3B/LC3B (LC3B) and Sequestosome1 (SQSTM1) based on AAV-R-CREon vector, which is a Cre recombinase-dependent gene-silencing system. Also, the effect of astrocyte-specific overexpression of LC3B on the neuropathology in AD (APP/PS1) mice was determined. Neuropathological alterations of AD mice with astrocytic autophagy dysfunction were observed by confocal microscopy and transmission electron microscope (TEM). Behavioral changes of mice were examined through novel object recognition test (NOR) and novel object place recognition test (NOPR). Results Here, we show that astrocytes, unlike neurons, undergo plastic changes in autophagic processes to remove Aβ. Aβ transiently induces expression of LC3B gene and turns on a prolonged transcription of SQSTM1 gene. The Aβ-induced astrocytic autophagy accelerates urea cycle and putrescine degradation pathway. Pharmacological inhibition of autophagy exacerbates mitochondrial dysfunction and oxidative stress in astrocytes. Astrocyte-specific knockdown of LC3B and SQSTM1 significantly increases Aβ plaque formation and GFAP-positive astrocytes in APP/PS1 mice, along with a significant reduction of neuronal marker and cognitive function. In contrast, astrocyte-specific overexpression of LC3B reduced Aβ aggregates in the brain of APP/PS1 mice. An increase of LC3B and SQSTM1 protein is found in astrocytes of the hippocampus in AD patients. Conclusions Taken together, our data indicates that Aβ-induced astrocytic autophagic plasticity is an important cellular event to modulate Aβ clearance and maintain cognitive function in AD mice.

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Caspase-dependent apoptosis induces reactivation and gliogenesis of astrocytes in adult mice

Cited by 2 publications

References 38 publications

Influenza vaccine is able to prevent neuroinflammation triggered by H7N7 IAV infection

Influenza vaccine is able to prevent neuroinflammation triggered by H7N7 IAV infection

Astrocytic autophagy plasticity modulates Aβ clearance and cognitive function in Alzheimer’s disease

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