GABA-mediated activated microglia induce neuroinflammation in the hippocampus of mice following cold exposure through the NLRP3 inflammasome and NF-κB signaling pathways

Lang, Limin; Xu, Bin; Yuan, Jianlin; Li, Shize; Lian, Shuai; Chen, Yan; Guo, Jiang; Yang, Huanmin

doi:10.1016/j.intimp.2020.106908

Cited by 26 publications

(18 citation statements)

References 54 publications

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“…Moreover, studies on mouse cortex in vivo have demonstrated that ramified microglia respond to current levels of GABAergic neurotransmission, as a surface application of the GABA receptor blocker, bicuculline, significantly increases microglial processes motility [152]. On the contrary, GABA evokes activation of microglia via the nucleotide oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and NF-κB signaling pathways, leading to a significant increase in the mRNA and protein levels of TNF-α, IL-6, and IL-1β in microglial cell line BV2 [153].…”

Section: Gabaergic Signaling In Microglial Dialogue With Neurons In Ad and Neuroinflammationmentioning

confidence: 99%

Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer’s Disease

Czapski

Strosznajder

2021

IJMS

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The physiological balance between excitation and inhibition in the brain is significantly affected in Alzheimer’s disease (AD). Several neuroactive compounds and their signaling pathways through various types of receptors are crucial in brain homeostasis, among them glutamate and γ-aminobutyric acid (GABA). Activation of microglial receptors regulates the immunological response of these cells, which in AD could be neuroprotective or neurotoxic. The novel research approaches revealed the complexity of microglial function, including the interplay with other cells during neuroinflammation and in the AD brain. The purpose of this review is to describe the role of several proteins and multiple receptors on microglia and neurons, and their involvement in a communication network between cells that could lead to different metabolic loops and cell death/survival. Our review is focused on the role of glutamatergic, GABAergic signaling in microglia–neuronal cross-talk in AD and neuroinflammation. Moreover, the significance of AD-related neurotoxic proteins in glutamate/GABA-mediated dialogue between microglia and neurons was analyzed in search of novel targets in neuroprotection, and advanced pharmacological approaches.

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Section: Gabaergic Signaling In Microglial Dialogue With Neurons In Ad and Neuroinflammationmentioning

confidence: 99%

Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer’s Disease

Czapski

Strosznajder

2021

IJMS

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“…After being stimulated by external stimuli, the p65 is phosphorylated by the protein kinases and then the phosphorylated NF-κB translocates to the nucleus and promotes the expression of downstream inflammatory factors ( 27 ). When the signaling pathway is activated, the ratio of pNF-κB/NF-κB is markedly elevated ( 28 ). To explore the effects of cinnamaldehyde on NF-κB signaling pathway in colonic tissues of newly weaned rats, western blot analysis was performed to determine the levels of the key proteins.…”

Section: Resultsmentioning

confidence: 99%

Cinnamaldehyde Promotes the Intestinal Barrier Functions and Reshapes Gut Microbiome in Early Weaned Rats

Mao

Lü³

et al. 2021

Front. Nutr.

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Cinnamaldehyde is an aromatic aldehyde isolated from the essential oil of cinnamon. It has been proved to possess various bioactivities such as anti-inflammation, anti-bacteria and antihypertensive. Nevertheless, early weaning could lead to intestinal stress, causing a range of intestinal health problems. The aim of this study is to explore the effects of cinnamaldehyde on gut barrier integrity, inflammatory responses, and intestinal microbiome of early weaned rats. In this study, treatment with cinnamaldehyde (100 or 200 mg/kg bodyweight/day) for 2 weeks significantly promoted the production of mucins in the colonic epithelial tissue of rats. Cinnamaldehyde supplementation significantly upregulated the expression of Muc2, TFF3 and the tight junction proteins (ZO-1, claudin-1, and occludin). Hematoxylin and eosin staining results showed that colonic histopathological changes were recovered by cinnamaldehyde supplementation. The mRNA expression of IL-6 and TNF-α were significantly decreased in the cinnamaldehyde groups while the TNF-α protein levels were significantly decreased in the two cinnamaldehyde groups. Cinnamaldehyde treatment obviously attenuated the activation of NF-κB signaling pathway in rat colonic tissue and suppressed the production of inflammatory cytokines. Furthermore, cinnamaldehyde supplementation remodeled the gut microbiome structure, at the genus level, Akkermansia, Bacteroides, Clostridium III, Psychrobacter, Intestinimonas were increased, whereas those of Ruminococcus, Escherichia/Shigella were obviously decreased in the cinnamaldehyde treated groups. These findings indicated that cinnamaldehyde could effectively enhance intestinal barrier integrity, ameliorate inflammatory responses and remodel gut microbiome in early weaned rats.

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“…Moreover, other authors also demonstrated that chloride intracellular channels act downstream of the potassium efflux-mitochondrial reactive oxygen species (ROS) axis to promote NLRP3 inflammasome activation [Daniels et al 2016, Tang et al 2017. These findings demonstrate that Cl − efflux and influx plays an important role for NLRP3 inflammasome activation, and could be even more important in neuroinflammation, as a consequence of GABA receptors activation, that modulate NLRP3 activation through changes in intracellular Cl − [Lang et al 2020, Omer et al 2020.…”

Section: Nlrp3 Activation Mediated By Ionic Imbalancementioning

confidence: 95%

Oxidative stress leads to severe phenotypes in sepsis through activation of NLRP3-pyroptosis

Beltrán-García

Osca-Verdegal

García‐Giménez

et al. 2022

Redox Experimental Medicine

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Oxidative stress is an important contributor in sepsis, one of the most important causes of death in intensive care units. Even though sepsis pathogenesis remains obscure due to its heterogenicity and complexity, there is increasing evidence that oxidants and antioxidants play a key role in its onset and progression. Recent evidence suggests that pyroptosis is required for defense against bacterial infection, and it is active in several cell types during sepsis. One of the most relevant mediators of pyroptosis is the NLRP3 inflammasome, been the oxidative stress/NLRP3 signaling pathway one of the main upstream signals involved in its activation. So, it is of special relevance to clarify how oxidative stress and antioxidants can modulate pyroptosis signals and therefore decrease the deleterious effects that both oxidative stress and pyroptosis-related cytokines can induce in the tissues during sepsis. Recent studies evaluating several antioxidants are promising, but further trials are needed to confirm their potential role as agents to block NLRP3 and mitigate the exacerbated inflammasome-related responses during sepsis.

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GABA-mediated activated microglia induce neuroinflammation in the hippocampus of mice following cold exposure through the NLRP3 inflammasome and NF-κB signaling pathways

Cited by 26 publications

References 54 publications

Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer’s Disease

Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer’s Disease

Cinnamaldehyde Promotes the Intestinal Barrier Functions and Reshapes Gut Microbiome in Early Weaned Rats

Oxidative stress leads to severe phenotypes in sepsis through activation of NLRP3-pyroptosis

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