Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

Abstract

Microglia are the main immune cells in the brain and have roles in brain homeostasis and neurological diseases. Mechanisms underlying microglia–neuron communication remain elusive. Here, we identified an interaction site between neuronal cell bodies and microglial processes in mouse and human brain. Somatic microglia–neuron junctions have a specialized nanoarchitecture optimized for purinergic signaling. Activity of neuronal mitochondria was linked with microglial junction formation, which was induced rapidly in response to neuronal activation and blocked by inhibition of P2Y12 receptors. Brain injury–induced changes at somatic junctions triggered P2Y12 receptor–dependent microglial neuroprotection, regulating neuronal calcium load and functional connectivity. Thus, microglial processes at these junctions could potentially monitor and protect neuronal functions.

The Antioxidant Peptide Salamandrin-I: First Bioactive Peptide Identified from Skin Secretion of Salamandra Genus (Salamandra salamandra)

“…In vitro cytotoxicity assays were made, to make preliminary assessment of toxicity, and to enable suitable concentration ranges to be used in future in vivo testing [64]. In this study, there was no statistically significant decrease in cell viability of human microglia treated with salamandrin-I as indicated by the resazurin assay up to 100 µM, suggesting an absence of cytotoxicity for this peptide ( Figure 6A).…”

“…In this study, there was no statistically significant decrease in cell viability of human microglia treated with salamandrin-I as indicated by the resazurin assay up to 100 µM, suggesting an absence of cytotoxicity for this peptide ( Figure 6A). Microglia are a type of glial cells located throughout the brain and spinal cord and account for 10%-15% of all glial cells found within the brain and constantly monitor neuronal functions through direct somatic contacts, and external neuroprotective effects [64]. In vitro non-cytotoxicity at high concentrations suggests the possibility of neuroprotective studies to assess whether the intrinsic antioxidant activity of the molecule can lead to cellular neuroprotection through regulation of microglia activity.…”

Chemogenetic manipulation of microglia inhibits neuroinflammation and neuropathic pain in mice

“…However, multiple lines of evidence have suggested that microglia can regulate neuronal activity. For example, microglia were able to dampen neuronal hyperactivity under seizure context (Eyo et al, 2014;Kato et al, 2016) or even under physiological conditions (Peng et al, 2019;Cserep et al, 2020).…”

Myelin Plasticity and Repair: Neuro-Glial Choir Sets the Tuning

“…They can adopt different phenotypes, with environmentdependent transcriptional profiles (Gosselin et al, 2014(Gosselin et al, , 2017, and proinflammatory to pro-regenerative polarization (Miron and Franklin, 2014), though a strict dichotomy is an inadequate vision (Ransohoff, 2016). Microglial cells are further sensitive to neuronal activity Liu et al, 2019;Stowell et al, 2019;Cserép et al, 2020). Altered microglia activity at different stages of life is associated with developmental and acquired neurological pathologies and can impair the plasticity-related process and cognitive function (Morris et al, 2013).…”