Glial cells, consisting of astrocytes, oligodendrocyte lineage cells, and microglia, account for >50% of the total number of cells in the mammalian brain. They play key roles in the modulation of various brain activities under physiological and pathological conditions. Although the typical morphological features and characteristic functions of these cells are well described, the organization of interconnections of the different glial cell populations and their impact on the healthy and diseased brain is not completely understood. Understanding these processes remains a profound challenge. Accumulating evidence suggests that glial cells can form highly complex interconnections with each other. The astroglial network has been well described. Oligodendrocytes and microglia may also contribute to the formation of glial networks under various circumstances. In this review, we discuss the structure and function of glial networks and their pathological relevance to central nervous system diseases. We also highlight opportunities for future research on the glial connectome.
Animals ; Neuroglia/physiology* ; Neurons/physiology* ; Astrocytes ; Microglia/physiology* ; Oligodendroglia ; Mammals

Gap junction is the aggregate of some intercellular channels, which allows ions and small molecules to transport or transfer between cells. There are about 20 proposed members of the connexin family found in mammalian tissues now, and more than 10 reported are expressed in the nervous system. The astrocytes and oligodendrocytes express some specific connexins. In the present article, we review the recent literatures to illustrate the importance of gap junction for the intercellular communication between glial cells, astrocytes and neurons, and neuronal cells, which is crucial for brain functions.
Brain ; metabolism ; physiology ; Connexins ; metabolism ; Gap Junctions ; metabolism ; physiology ; Humans ; Neuroglia ; metabolism ; physiology ; Neurons ; metabolism ; physiology

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of therapies. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions, including chronic pain. Astrocytes regulate nociceptive synaptic transmission and network function via neuron-glia and glia-glia interactions to exaggerate pain signals under chronic pain conditions. It is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic pain. Therefore, this review presents our current understanding of the roles of astrocytes in chronic pain, how they regulate nociceptive responses, and their cellular and molecular mechanisms of action.
Humans ; Astrocytes/pathology* ; Chronic Pain/pathology* ; Neuroglia/physiology* ; Neurons/physiology* ; Synaptic Transmission ; Chronic Disease

Our brains are composed of two distinct cell types: neurons and glia. Emerging data from recent investigations show that glial cells, especially astrocytes and microglia, are able to regulate synaptic transmission and thus brain information processing. This suggests that, not only neuronal activity, but communication between neurons and glia also plays a key role in brain function. Thus, it is currently well known that the physiology and pathophysiology of brain function can only be completely understood by considering the interplay between neurons and glia. However, it has not yet been possible to dissect glial cell type-specific roles in higher brain functions in vivo. Meanwhile, the recent development of optogenetics techniques has allowed investigators to manipulate neural activity with unprecedented temporal and spatial precision. Recently, a series of studies suggested the possibility of applying this cutting-edge technique to manipulate glial cell activity. This review briefly discusses the feasibility of optogenetic glia manipulation, which may provide a technical innovation in elucidating the in vivo role of glial cells in complex higher brain functions.
Astrocytes ; Automatic Data Processing ; Brain ; Humans ; Microglia ; Neuroglia* ; Neurons ; Optogenetics* ; Physiology ; Research Personnel ; Synapses ; Synaptic Transmission

Diabetes patients tend to have the gastrointestinal motility disorder. Although the relationship between the motility disorder and both the neurons and Cajal cells in the enteric nervous system (ENS) is well established, little is known about the role of enteric glial cells (EGCs) in gastric motility in diabetes. This study aimed to examine the expression of the glial marker S100B and morphology of EGCs in gastric tissues and the relationship between activated EGCs and the damage of gastric emptying in diabetic models. The diabetic model of rat was induced with 1% streptozotocin (STZ). The model rats at 7-14 days and at 56-63 days were defined as early diabetic rats and advanced diabetic rats, respectively, and normal rats at the two time periods served as their corresponding controls. The gastric emptying rate of the rats was tested by using the phenol red solution. The ultrastructure of EGCs in the gastric antrum was observed by the transmission electron microscopy, and the expression of S100B in the myenteric plexus was immunohistochemically detected. The results showed that the gastric emptying rate was significantly increased in the early diabetic rats and decreased in the advanced diabetic rats when compared with their corresponding control rats (P<0.01 for both). The ultrastructure of EGCs was mostly normal in both the early diabetic and control groups. Vacuolization of mitochondria and expansion of endoplasmic reticulum occurred in both the advanced diabetic group and its control group, and even the structure of smooth muscle cells and intestinal neurons was destroyed in the advanced diabetic group. The expression level of S100B in the advanced diabetic group was significantly decreased compared with its control group (P<0.05). It was obviously increased in the early diabetic control group when compared with the advanced diabetic control group (P<0.05). However, there was no significant difference in the S100B expression between the early diabetic group and its control group (P>0.05). The findings suggested that the gastric motility dysfunction in diabetes may be associated with the changes of morphology and number of EGCs in the myenteric plexus.
Animals ; Diabetes Mellitus, Experimental ; pathology ; Gastrointestinal Motility ; physiology ; Male ; Neuroglia ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo review the relationship between the immune system and the mechanism of pain. Data sources Related researches published in the period of 1987-2005 were systematically reviewed. Study selection Articles about the immune system and pain were selected. Data extraction Data were mainly extracted from 74 articles which are listed in the reference section of this review.

RESULTSPain was classically viewed as being mediated solely by neurons. However, growing evidence has showed the possible relationships between the immune system and the central nervous system. In this article, we reviewed the role of the immune system in the development of pain, together with the importance of the glia in this process. These findings suggest a novel approach to pain control in the future.

CONCLUSIONSThe immune system plays a potential but important role in the development of pain.

Animals ; Brain ; immunology ; Humans ; Immune System ; physiology ; Interleukin-1 ; physiology ; Neuroglia ; physiology ; Pain ; etiology ; immunology ; TRPV Cation Channels ; physiology ; Tumor Necrosis Factor-alpha ; physiology ; Wounds and Injuries ; immunology

Spinal cord injuries are damages that result in complete or partial loss of sensation and/or mobility and affect the life qualities of many patients. Their pathophysiology includes primary and secondary processes, which are related with the activation of astrocytes and microgliacytes and the degeneration of oligodendrocytes. Although transplantation of embryonic stem cells or neural progenitor cells is an attractive strategy for repair of the injured central nervous system (CNS), transplantation of these cells alone for acute spinal cord injuries has not resulted in robust axon regeneration beyond the injury sites. This may be due to the progenitor cells differentiating to the cell types that support axon growth poorly and/or their inability to modify the inhibitory environment of adult CNS after injury. Recent studies indicate that transplantation of glial progenitor cells has exhibited beneficial effects on the recovery and promising future for the therapy strategy of spinal cord injury. In this review, we summarized the data from recent literature regarding glial implications in transplantation therapy of spinal cord injury.
Animals ; Astrocytes ; transplantation ; Humans ; Microglia ; transplantation ; Neuroglia ; physiology ; transplantation ; Oligodendroglia ; transplantation ; Spinal Cord Injuries ; surgery ; Stem Cell Transplantation

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
Animals ; Mice ; Dark Adaptation ; Light ; Retina ; Retinal Cone Photoreceptor Cells/metabolism* ; Adaptation, Ocular ; Neuroglia/physiology* ; Cell Communication ; Thyroid Hormones

Olfactory ensheathing cells (OECs) are a unique type of glia with common properties of astrocyte and Schwann cells. Cultured OECs have two morphological phenotypes, astrocyte-like OECs and Schwann cell-like OECs. Reversible changes have been found between these two morphological phenotypes. However, the molecular mechanism underlying the regulation of these reversible changes is still unknown. The aim of this paper is to establish a method for the morphology plasticity of cultured OECs, and investigate the underlying mechanism. Using the primary culture of OECs and immunocytochemistry, the morphology of OECs was observed under serum, serum free media or dB-cAMP drug treatment. Statistical analysis was performed to test differences among the percentages of OEC subtypes under these conditions. The results showed that under serum free media, (95.2±3.7)% of OECs showed Schwann cell-like morphology, and (4.8±3.7)% of OECs showed astrocyte-like morphology; however, under 10% serum media, (42.5±10.4)% of OECs exhibited Schwann cell-like morphology, and (57.5±10.4)% of OECs exhibited astrocyte-like morphology. When media was changed back to serum free media for 24 h, (94.8±5.0)% of OECs showed Schwann cell-like morphology, and (5.2±5.0)% of OECs showed astrocyte-like morphology. Furthermore, culture condition with or without serum did not affect the expression of OEC cell marker, p-75 and S-100. Finally, dB-cAMP, an analog of cAMP, through inhibiting the formation of F-actin stress fibers and focal adhesion, induced the morphology switch from astrocyte-like to Schwann cell-like morphology under serum condition, promoted the branches and the growth of processes. These results suggest that serum induces the morphology plasticity of cultured OECs, which is mediated by cytoplasmic cAMP level through regulating the formation of F-actin stress fibers and focal adhesion.
Animals ; Astrocytes ; cytology ; physiology ; Cells, Cultured ; Culture Media ; pharmacology ; Cyclic AMP ; physiology ; Male ; Neuroglia ; cytology ; physiology ; Olfactory Bulb ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley ; Schwann Cells ; cytology ; physiology ; Serum ; physiology