Proinflammatory activation of microglia in the cerebellum hyperexcites Purkinje cells to trigger ataxia

Xie, Shutao; Fan, Wen-Chu; Zhao, Xian-Sen; Ma, Xiaoyang; Li, Zelin; Zhao, Yan-Ran; Fa, Yang; Shi, Ying; Hui, Rutai; Cui, Zhi-San; Chen, Junyi; Li, Hongzhao; Yan, Chao; Zhang, Qipeng; Wang, Jianjun; Zhang, Xiaoyang; Gu, Xiaoping; Ma, Zhengliang; Zhu, Jing-Ning

doi:10.1016/j.phrs.2023.106773

Cited by 6 publications

(2 citation statements)

References 70 publications

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“…However, microglia function varies with time after TBI and across TBI models, with most activated microglia displaying a mix of pro‐ and anti‐inflammatory roles. Therefore, early therapeutic interventions for TBI should aim not only to suppress microglial activation but also to modulate the microglial response to promote inflammation resolution post‐injury 9,28‐30 …”

Section: Discussionmentioning

confidence: 99%

“…For example, microglia may express CD16/32, CD86, and nod‐like receptor (NLR) family member NLRP3, producing inflammatory cytokines like iNOS and IL‐1β that aggravate injury. Conversely, microglia can also express CD206 Arg‐1, and Ym1, releasing anti‐inflammatory cytokines like IL‐10 and TGF‐β1, which help clear hematomas and cellular debris and mitigate neuroinflammation 8,9 . Therefore, understanding microglia heterogeneity offers valuable insight into the pathogenesis of secondary CNS injuries.…”

Section: Introductionmentioning

confidence: 99%

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CD300LF⁺ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

Lu,

Liu,

Wang

et al. 2024

CNS Neurosci Ther

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IntroductionThe diversity in microglial phenotypes and functions following traumatic brain injury (TBI) is poorly characterized. The aim of this study was to explore precise targets for improving the prognosis of TBI patients from a microglial perspective.ObjectivesTo assess whether the prognosis of TBI can be improved by modulating microglia function.ResultsIn CD300LF‐deficient mice, we observed an increase in glial cell proliferation, more extensive neuronal loss, and worsened neurological function post‐TBI. Transcriptomic comparisons between CD300LF‐positive and CD300LF‐negative microglia illuminated that the neuroprotective role of CD300LF is principally mediated by the inhibition of the STING signaling pathway. In addition, this protective effect can be augmented using the STING pathway inhibitor C‐176.ConclusionsOur research indicates that CD300LF reduces neuroinflammation and promotes neurological recovery after TBI, and that microglia are integral to the protective effects of CD300LF in this context. In summary, our findings highlight CD300LF as a critical molecular regulator modulating the adverse actions of microglia following acute brain injury and propose a novel therapeutic approach to enhance outcomes for patients with TBI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD300LF⁺ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

Lu,

Liu,

Wang

et al. 2024

CNS Neurosci Ther

View full text Add to dashboard Cite

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Histaminergic Innervation of the Ventral Anterior Thalamic Nucleus Alleviates Motor Deficits in a 6-OHDA-Induced Rat Model of Parkinson’s Disease

Xu,

Xi,

Zhou

et al. 2024

Neurosci. Bull.

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The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson’s disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K+ channels, or Ca2+-activated K+ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.

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The Neuroimmune System and the Cerebellum

Gruol

2023

Cerebellum

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The recognition that there is an innate immune system of the brain, referred to as the neuroimmune system, that preforms many functions comparable to that of the peripheral immune system is a relatively new concept and much is yet to be learned. The main cellular components of the neuroimmune system are the glial cells of the brain, primarily microglia and astrocytes. These cell types preform many functions through secretion of signaling factors initially known as immune factors but referred to as neuroimmune factors when produced by cells of the brain. The immune functions of glial cells play critical roles in the healthy brain to maintain homeostasis that is essential for normal brain function, to establish cytoarchitecture of the brain during development, and, in pathological conditions, to minimize the detrimental effects of disease and injury and promote repair of brain structure and function. However, dysregulation of this system can occur resulting in actions that exacerbate or perpetuate the detrimental effects of disease or injury. The neuroimmune system extends throughout all brain regions, but attention to the cerebellar system has lagged that of other brain regions and information is limited on this topic. This article is meant to provide a brief introduction to the cellular and molecular components of the brain immune system, its functions, and what is known about its role in the cerebellum. The majority of this information comes from studies of animal models and pathological conditions, where upregulation of the system facilitates investigation of its actions.

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Proinflammatory activation of microglia in the cerebellum hyperexcites Purkinje cells to trigger ataxia

Cited by 6 publications

References 70 publications

CD300LF⁺ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

CD300LF⁺ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

Histaminergic Innervation of the Ventral Anterior Thalamic Nucleus Alleviates Motor Deficits in a 6-OHDA-Induced Rat Model of Parkinson’s Disease

The Neuroimmune System and the Cerebellum

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Proinflammatory activation of microglia in the cerebellum hyperexcites Purkinje cells to trigger ataxia

Cited by 6 publications

References 70 publications

CD300LF+ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

CD300LF+ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

Histaminergic Innervation of the Ventral Anterior Thalamic Nucleus Alleviates Motor Deficits in a 6-OHDA-Induced Rat Model of Parkinson’s Disease

The Neuroimmune System and the Cerebellum

Contact Info

Product

Resources

About

CD300LF⁺ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

CD300LF⁺ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway