Divergent Crosstalk Between Microglia and T Cells in Brain Cancers: Implications for Novel Therapeutic Strategies.

: Brain cancers represent a formidable oncological challenge characterized by their aggressive nature and resistance to conventional therapeutic interventions. The tumor microenvironment has emerged as a critical determinant of tumor progression and treatment efficacy. Within this complex ecosystem, microglia and macrophages play fundamental roles, forming intricate networks with peripheral immune cell populations, particularly T cells.

Microglia enhance post-anesthesia neuronal activity by shielding inhibitory synapses.

Microglia are resident immune cells of the central nervous system and play key roles in brain homeostasis. During anesthesia, microglia increase their dynamic process surveillance and interact more closely with neurons. However, the functional significance of microglial process dynamics and neuronal interaction under anesthesia is largely unknown.

Peptide-mediated targeted delivery of SOX9 nanoparticles into astrocytes ameliorates ischemic brain injury.

Astrocytes are highly activated following brain injuries, and their activation influences neuronal survival. Additionally, SOX9 expression is known to increase in reactive astrocytes. However, the role of SOX9 in activated astrocytes following ischemic brain damage has not been clearly elucidated yet.

Chemogenetic approaches reveal dual functions of microglia in seizures.

Microglia are key players in maintaining brain homeostasis and exhibit phenotypic alterations in response to epileptic stimuli. However, it is still relatively unknown if these alterations are pro- or anti-epileptic. To unravel this dilemma, we employed chemogenetic manipulation of microglia using the artificial Gi-Dreadd receptor within a kainic acid (KA) induced murine seizure model.

Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity.

Microglia are highly dynamic immune cells of the central nervous system (CNS). Microglial processes interact with neuronal elements constantly on the order of minutes. The functional significance of this acute microglia-neuron interaction and its potential role in the context of pain is still largely unknown.

Chemogenetic and Optogenetic Manipulations of Microglia in Chronic Pain.

Chronic pain relief remains an unmet medical need. Current research points to a substantial contribution of glia-neuron interaction in its pathogenesis. Particularly, microglia play a crucial role in the development of chronic pain.

The voltage-gated proton channel Hv1 promotes microglia-astrocyte communication and neuropathic pain after peripheral nerve injury.

Activation of spinal cord microglia contributes to the development of peripheral nerve injury-induced neuropathic pain. However, the molecular mechanisms underlying microglial function in neuropathic pain are not fully understood. We identified that the voltage-gated proton channel Hv1, which is functionally expressed in spinal microglia, was significantly increased after spinal nerve transection (SNT).

Optogenetic activation of spinal microglia triggers chronic pain in mice.

Spinal microglia are highly responsive to peripheral nerve injury and are known to be a key player in pain. However, there has not been direct evidence showing that selective microglial activation in vivo is sufficient to induce chronic pain. Here, we used optogenetic approaches in microglia to address this question employing CX3CR1creER/+: R26LSL-ReaChR/+ transgenic mice, in which red-activated channelrhodopsin (ReaChR) is inducibly and specifically expressed in microglia.

Chemogenetic manipulation of microglia inhibits neuroinflammation and neuropathic pain in mice.

Microglia play an important role in the central sensitization and chronic pain. However, a direct connection between microglial function and pain development in vivo remains incompletely understood. To address this issue, we applied chemogenetic approach by using CXCR1:R26 transgenic mice to enable expression of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (Gi DREADD) in microglia.

Extracorporeal shockwave therapy enhances peripheral nerve remyelination and gait function in a crush model.

Background: Conservative treatment, such as electrical stimulation and steroid injection, have been employed in an attempt to improve symptoms after peripheral nerve injury, without significant success. Although non-invasive and safe extracorporeal shockwave therapy (ESWT) can be a practical alternative, the therapeutic effects of ESWT on peripheral nerve remyelination has not been established.

Objectives: To investigate the effects of ESWT on peripheral nerve remyelination and gait function for 5 weeks in a sciatic nerve crush model.

Author Correction: CD200R/Foxp3-mediated signalling regulates microglial activation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PINK1 mediates spinal cord mitophagy in neuropathic pain.

Mitophagy is the selective engulfment of mitochondria by autophagosomes and the subsequent mitochondrial catabolism by lysosomes. Evidence has suggested an important role for mitochondrial dynamics and mitophagic flux in the development of many different neurodegenerative diseases. The potential role of the mechanism underlying mitochondrial dynamics and mitophagic flux as it may relate to neuropathic pain is not well understood.

Impaired Autophagy of GABAergic Interneurons in Neuropathic Pain.

Neuropathic pain (NP) is caused by lesions of the peripheral fibers and central neurons in the somatosensory nervous system and affects 7-10% of the general population. Although the distinct cause of neuropathic pain has been investigated in primary afferent neurons over the years, pain modulation by central sensitization remains controversial. NP is believed to be driven by cell type-specific spinal synaptic plasticity in the dorsal horn.

Uncoupled Endothelial Nitric Oxide Synthase Enhances p-Tau in Chronic Traumatic Encephalopathy Mouse Model.

Aims: Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease thought to be caused by repetitive traumatic brain injury (TBI) and subconcussive injuries. While hyperphosphorylation of tau (p-Tau), which is attributed to astrocytic tangles (ATs) and neurofibrillary tangles, is known to be involved in CTE, there are limited neuropathological or molecular data. By utilizing repetitive mild TBI (rmTBI) mouse models, our aim was to examine the pathological changes of CTE-associated structures, specifically the ATs.

P2Y12R-Dependent Translocation Mechanisms Gate the Changing Microglial Landscape.

Microglia are an exquisitely tiled and self-contained population in the CNS that do not receive contributions from circulating monocytes in the periphery. While microglia are long-lived cells, the extent to which their cell bodies are fixed and the molecular mechanisms by which the microglial landscape is regulated have not been determined. Using chronic in vivo two-photon imaging to follow the microglial population in young adult mice, we document a daily rearrangement of the microglial landscape.

Primary cilia modulate TLR4-mediated inflammatory responses in hippocampal neurons.

Background: The primary cilium is an organelle that can act as a master regulator of cellular signaling. Despite the presence of primary cilia in hippocampal neurons, their function is not fully understood. Recent studies have demonstrated that the primary cilium influences interleukin (IL)-1β-induced NF-κB signaling, ultimately mediating the inflammatory response.

Expression of granulocyte colony-stimulating factor 3 receptor in the spinal dorsal horn following spinal nerve ligation-induced neuropathic pain.

In previous studies that have profiled gene expression in patients with complex regional pain syndrome (CRPS), the expression of granulocyte colony-stimulating factor 3 receptor (G‑CSFR) was elevated, as were a number of pain‑associated genes. The present study determined the expression of G‑CSFR and the mechanisms by which it may affect hypersensitivity, focusing on the signal transducer and activator of transcription 3 (STAT3)/transient receptor potential cation channel subfamily V 1 (TRPV1) signaling pathway in particular, which is an important mediator of pain. Following L5 spinal nerve ligation (SNL) surgery, the protein and mRNA levels of G‑CSFR increased in the ipsilateral spinal dorsal horn when compared with the sham and/or contralateral control.

Expression of PGC1α in glioblastoma multiforme patients.

Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) is a key modulator of mitochondrial biogenesis. It is a coactivator of multiple transcription factors and regulates metabolic processes. However, little is known about the expression and function of PGC1α in glioblastoma multiforme (GBM), the most prevalent and invasive type of brain tumor.

Astrocytic Expression of CTMP Following an Excitotoxic Lesion in the Mouse Hippocampus.

Akt (also known as protein kinase B, PKB) has been seen to play a role in astrocyte activation of neuroprotection; however, the underlying mechanism on deregulation of Akt signaling in brain injuries is not fully understood. We investigated the role of carboxy-terminal modulator protein (CTMP), an endogenous Akt inhibitor, in brain injury following kainic acid (KA)-induced neurodegeneration of mouse hippocampus. In control mice, there was a weak signal for CTMP in the hippocampus, but CTMP was markedly increased in the astrocytes 3 days after KA treatment.

Effect of Botulinum Toxin Type A on TGF-β/Smad Pathway Signaling: Implications for Silicone-Induced Capsule Formation.

Background: One of the most serious complications of breast surgery using implants is capsular contracture. Several preventive treatments have been introduced; however, the mechanism of capsule formation has not been resolved completely. The authors previously identified negative effects of botulinum toxin type A on capsule formation, expression of transforming growth factor (TGF)-β1, and differentiation of fibroblasts into myofibroblasts.

CD200R/Foxp3-mediated signalling regulates microglial activation.

The heterogeneity of microglial functions have either beneficial or detrimental roles in specific physiological or pathological environments. However, the details of what transcriptional mechanisms induce microglia to take beneficial phenotypes remain unknown. Here, we report that Foxp3 is essential for beneficial outcome of the microglial response and depends upon signalling by the immunoglobulin CD200 through its receptor (CD200R).

Altered expression of KCC2 in GABAergic interneuron contributes prenatal stress-induced epileptic spasms in infant rat.

Long-term stress during pregnancy causes neurologic deficits to offspring with altered gamma-aminobutyric acid (GABA) system in the brain. However, it is not clear how prenatal stress affects the maturing GABAergic interneurons and the resulting abnormalities in infantile seizures. Here, we showed that prenatal stress alters the maturation of GABA inhibitory system using a seizure model induced by prenatal stress.