Glial cells in the central nervous system (CNS) are composed of oligodendrocytes, astrocytes and microglia. They contribute more than half of the total cells of the CNS, and are essential for neural development and functioning. Studies on the fate specification, differentiation, and functional diversification of glial cells mainly rely on the proper use of cell- or stage-specific molecular markers. However, as cellular markers often exhibit different specificity and sensitivity, careful consideration must be given prior to their application to avoid possible confusion. Here, we provide an updated overview of a list of well-established immunological markers for the labeling of central glia, and discuss the cell-type specificity and stage dependency of their expression.
Neuroglia/metabolism* ; Central Nervous System ; Oligodendroglia/metabolism* ; Astrocytes/metabolism* ; Microglia

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Magnolia ; White Matter ; Brain Ischemia/metabolism* ; Oligodendroglia/metabolism*

Cerebral small vessel disease (CSVD) is one of the most prevalent pathologic processes affecting 5% of people over 50 years of age and contributing to 45% of dementia cases. Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion, impaired cerebral vascular reactivity, and leakage of the blood-brain barrier in CSVD. However, the pathogenesis of CSVD remains elusive thus far, and no radical treatment has been developed. NG2 glia, also known as oligodendrocyte precursor cells, are the fourth type of glial cell in addition to astrocytes, microglia, and oligodendrocytes in the mammalian central nervous system. Many novel functions for NG2 glia in physiological and pathological states have recently been revealed. In this review, we discuss the role of NG2 glia in CSVD and the underlying mechanisms.
Animals ; Neuroglia/metabolism* ; Central Nervous System/metabolism* ; Astrocytes/metabolism* ; Oligodendroglia/metabolism* ; Cerebral Small Vessel Diseases/metabolism* ; Antigens/metabolism* ; Mammals/metabolism*

Myelin-forming oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS) are essential for structural and functional homeostasis of nervous tissue. Albeit with certain similarities, the regulation of CNS and PNS myelination is executed differently. Recent advances highlight the coordinated regulation of oligodendrocyte myelination by amino-acid sensing and growth factor signaling pathways. In this review, we discuss novel insights into the understanding of differential regulation of oligodendrocyte and Schwann cell biology in CNS and PNS myelination, with particular focus on the roles of growth factor-stimulated RHEB-mTORC1 and GATOR2-mediated amino-acid sensing/signaling pathways. We also discuss recent progress on the metabolic regulation of oligodendrocytes and Schwann cells and the impact of their dysfunction on neuronal function and disease.
Amino Acids ; Myelin Sheath/metabolism* ; Schwann Cells/metabolism* ; Oligodendroglia/metabolism* ; Signal Transduction ; Intercellular Signaling Peptides and Proteins/metabolism*

Schizophrenia is likely to be a multifactorial disorder, consequence of alterations in gene and protein expression since the neurodevelopment that together to environmental factors will trigger the establishment of the disease. In the post-genomic era, proteomics has emerged as a promising strategy for revealing disease and treatment biomarkers as well as a tool for the comprehension of the mechanisms of schizophrenia pathobiology. Here, there is a discussion of the potential pathways and structures that are compromised in schizophrenia according to proteomic findings while studying five distinct brain regions of post-mortem tissue from schizophrenia patients and controls. Proteins involved in energy metabolism, calcium homeostasis, myelinization, and cytoskeleton have been recurrently found to be differentially expressed in schizophrenia brains. These findings may encourage new studies on the understanding of schizophrenia biochemical pathways and even new potential drug targets.
Biomarkers ; Brain ; Calcium ; Comprehension ; Cytoskeleton ; Energy Metabolism ; Homeostasis ; Humans ; Myelin Sheath ; Oligodendroglia ; Proteins ; Proteomics ; Schizophrenia

In the past decade, structural, molecular, and functional changes in glial cells have become a major focus in the search for the neurobiological foundations of schizophrenia. Glial cells, consisting of oligodendrocytes, astrocytes, microglia, and nerve/glial antigen 2-positive cells, constitute a major cell population in the central nervous system. There is accumulating evidence of reduced numbers of oligodendrocytes and altered expression of myelin/oligodendrocyte-related genes that might explain the white matter abnormalities and altered inter- and intra-hemispheric connectivities that are characteristic signs of schizophrenia. Astrocytes play a key role in the synaptic metabolism of neurotransmitters ; thus, astrocyte dysfunction may contribute to certain aspects of altered neurotransmission in schizophrenia. Increased densities of microglial cells and aberrant expression of microglia-related surface markers in schizophrenia suggest that immunological/inflammatory factors are of considerable relevance to the pathophysiology of psychosis. This review describes current evidence for the multifaceted role of glial cells in schizophrenia and discusses efforts to develop glia-directed therapies for the treatment of the disease.
Astrocytes ; Central Nervous System ; Foundations ; Metabolism ; Microglia ; Neuroglia* ; Neurotransmitter Agents ; Oligodendroglia ; Psychotic Disorders ; Schizophrenia* ; Synaptic Transmission

The self-renewal and multipotent potentials in neural stem cells (NSCs) maintain the normal physiological functions of central nervous system (CNS). The abnormal differentiation of NSCs would lead to CNS disorders. However, the mechanisms of how NSCs differentiate into astrocytes, oligodendrocytes (OLs) and neurons are still unclear, which is mainly due to the complexity of differentiation processes and the limitation of the cell separation method. In this study, we modeled the dynamics of neural cell interactions in a systemic approach by mining the high-throughput genomic and proteomic data, and identified 8615 genes that are involved in various biological processes and functions with significant changes during the differentiation processes. A total of 1559 genes are specifically expressed in neural cells, in which 242 genes are NSC specific, 215 are astrocyte specific, 551 are OL specific, and 563 are neuron specific. In addition, we proposed 57 transcriptional regulators specifically expressed in NSCs may play essential roles in the development courses. These findings provide more comprehensive analysis for better understanding the endogenous mechanisms of NSC fate determination.
Animals ; Astrocytes ; cytology ; metabolism ; Cell Differentiation ; genetics ; Gene Expression Profiling ; Gene Regulatory Networks ; Mice ; Neural Stem Cells ; cytology ; metabolism ; Oligodendroglia ; cytology ; metabolism ; Protein Interaction Mapping

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.
Animals ; Cell Differentiation ; Flavanones ; Mice ; Mice, Inbred C57BL ; Myelin Sheath/metabolism* ; Oligodendroglia/metabolism* ; Rats ; Remyelination ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism*

OBJECTIVETo study the effect of adenovirus-mediated basic fibroblast growth factor(FGF-2) gene transfer in vivo on oligodendrocyte cell numbers throughout ventrolateral white matter following spinal cord injury in rats.

METHODSThirty-two adult female Sprague Dawley rats were injured with the Infinite Horizon Impactor, and then were randomly assigned to four groups: FGF-2-Adts high-titer group (1.27x10(7) pfu/rat), FGF-2-Adts intermediate-titre group (6.37x10(6) pfu/rat), FGF-2-Adts low-titer group (3.18 x 10(6) pfu/rat), and green fluorescent protein (GFP)-Adts group (5.9x10(7) pfu/rat). The transgenic expression in vivo was detected with fluorescence microscopy. The locomotor function of the hindlimbs of rats was evaluated using Rivlin plate. Slides mounted with tissue sections were processed for immunohistochemical detection and quantification of oligodendrocytes (CC1(+)) in the ventral lateral funiculi (VLF) of injured spinal cords.

RESULTSOne week after spinal cord injury, GFP showed that many cells had expressed objective gene in vivo and the angles of the occlusal plane of rats in FGF-2 groups were significantly higher than in GFP-Adts group. Also, there was a significant difference among the FGF-2-Adts treatment groups for the volume of gray matter sparing. However, there were no significant differences for total white matter sparing. Stereological quantification of total CC1(+) cell numbers in the spared VLF showed a significant reduction in numbers with GFP controls compared to all other groups 4 weeks after injury. In contrast, the FGF-2 Adts intermediate-titer group had significantly more CC1(+) cells when compared to both the FGF-2-Adts high- and low-titer groups.

CONCLUSIONAdenovirus-mediated FGF-2 gene transfer can promote the functional recovery of the injured spinal cord by enhancing the proliferation and/or differentiation of oligodendrocytes.

Adenoviridae ; genetics ; Animals ; Disease Models, Animal ; Female ; Fibroblast Growth Factor 2 ; genetics ; metabolism ; Genetic Therapy ; Oligodendroglia ; pathology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; metabolism ; physiopathology ; therapy ; Transfection

Insufficient remyelination due to impaired oligodendrocyte precursor cell (OPC) differentiation and maturation is strongly associated with irreversible white matter injury (WMI) and neurological deficits. We analyzed whole transcriptome expression to elucidate the potential role and underlying mechanism of action of lipocalin-2 (LCN2) in OPC differentiation and WMI and identified the receptor SCL22A17 and downstream transcription factor early growth response protein 1 (EGR1) as the key signals contributing to LCN2-mediated insufficient OPC remyelination. In LCN-knockdown and OPC EGR1 conditional-knockout mice, we discovered enhanced OPC differentiation in developing and injured white matter (WM); consistent with this, the specific inactivation of LCN2/SCl22A17/EGR1 signaling promoted remyelination and neurological recovery in both atypical, acute WMI due to subarachnoid hemorrhage and typical, chronic WMI due to multiple sclerosis. This potentially represents a novel strategy to enhance differentiation and remyelination in patients with white matter injury.
Mice ; Animals ; Remyelination/physiology* ; Oligodendrocyte Precursor Cells/metabolism* ; White Matter ; Subarachnoid Hemorrhage/metabolism* ; Lipocalin-2/metabolism* ; Early Growth Response Protein 1/metabolism* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Cell Differentiation/physiology* ; Brain Injuries/metabolism*