Glial cells are a large group of cells in the nervous system that are distinct from neurons and are 10-50 times more numerous. For a long time glial cells were considered a kind of "glue" in the nervous system, only to bind neurons and fill the nervous system. As neuroscience has advanced in recent decades, neurobiologists have discovered that glial cells perform a variety of functions and are involved in higher functions such as memory, cognition, neurodevelopmental and neurodegenerative diseases, and even aging. According to PubMed, the 10-year growth rate of glial cell related papers in China is 270%, much higher than the global average growth rate of 140%, indicating that the research momentum of glial cells in China is very strong. This issue of Progress in Biochemistry and Biophysics has features more than 19 papers on glial cells. It covers the aspects of physiological and pathological functions of glial cells. The publication of this issue will promote the scientific research on glial cells in China and serve as a reference for the China Brain Project.
Cellular conversion is a process of genetic reprogramming by various methods to induce the direct transformation of one type of cell into another without going through other intermediate states. Neuronal loss is a common pathological process in a variety of neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and stroke. Neuronal loss is usually irreversible and causes motor, sensory, and psychiatric symptoms. Since the human central nervous system has limited capacity for neuronal regeneration, therapeutic strategies that use glial cells (astrocytes, microglia, and oligodendrocyte precursor cells) to transdifferentiate into functional neurons in situ of neuronal loss and integrate them into neural networks have received much attention. In recent years, successful conversion of glia-to-neuron by manipulating the gene expression of key transcription factors in neuronal fate determination in glial cells has been discovered. Nevertheless, there is still some controversy about the scientific validity of some research technologies, the rationality of judgment criteria, and the self-consistency between experimental results and conclusions. This article reviews the discovery and development of glia-to-neuron conversion and takes astrocytes, microglia, and oligodendrocyte progenitor cells as examples to summarize the important findings of glia-to-neuron conversion with discussion and perspective.
Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive leukoencephalopathy caused by any of EIF2B1-5 mutations, encoding five subunits α-ε of eukaryotic translation initiation factor 2B (eIF2B). The clinical phenotype of the disease varies greatly. The typical manifestation is progressive motor function regression, which can be accompanied by ataxia and epilepsy and susceptible to episodic aggravation of stress such as fever and trauma. Imaging showed progressive liquefaction of cerebral white matter. Autopsy neuropathology is characterized by extensive white matter sparseness and cystic degeneration, no reactive proliferation of glial cells, abnormal astrocyte morphology, overexpression of progenitor cell markers Nestin and GFAPδ, and increased number of oligodendrocyte precursor cells and decreased mature oligodendrocytes, foamed and increased apoptosis. The VWM gene EIF2B1-5 is housekeeping gene, but most patients usually only have white matter involvement. A small number of fetal and early infantile patients may have multisystem involvement, and adult female patients may have ovarian dysfunction. It is currently believed that astrocytes play a central role in the pathogenesis of VWM. Pathological astrocytes cause secondary oligodendrocyte maturation disorder and abnormal myelination, which in turn lead to white matter lesions. Other disease mechanisms, including excessive activation of the unfolded protein response (UPR) after endoplasmic reticulum stress, mitochondrial dysfunction, and autophagy inhibition, are not fully understood.
DENG Jiong, WU Ye.Reviews and Monographs: Research Progress of Leukoencephalopathy With Vanishing White Matter[J].,2022,49(11):2099-2106.Export: BibTexEndNote
Metachromatic leukodystrophy (MLD) is a rare hereditary leukoencephalopathy caused by arylsulfatase A (ARSA) gene mutation. There are individual differences in the clinical manifestations and disease progression speed of MLD, but almost all patients will eventually have complete loss of motor and cognitive functions. Clinically, patients are divided into late infantile onset, juvenile onset and adult onset according to their age of onset and severity of illness. The clinical diagnosis of MLD includes progressive neurological regression and typical magnetic resonance imaging (MRI) findings. Its clinical manifestations are similar to many diseases, and it needs to be differentiated from other leukoencephalopathies and lysosomal storage diseases. There is no effective treatment for MLD. Hematopoietic stem cell transplantation or bone marrow transplantation, enzyme replacement therapy and gene therapy are the research hotspots of MLD treatment. At present, only symptomatic support treatment can be carried out for patients. Recent studies have found that intrathecal injection of recombinant human arylsulfatase A (rhASA) could delay the progress of the disease. Effective prenatal molecular diagnosis for MLD families is the main method to prevent the occurrence of MLD.
CHEN Li, WANG Jing-Min.Reviews and Monographs: Research Progress of Metachromatic Leukodystrophy[J].,2022,49(11):2107-2114.Export: BibTexEndNote
Pelizaeus-Merzbacher disease (PMD) is the most common disease of hypomyelination disorder. Most of the patients displayed with development delay especially motor delay, nystagmus and hypotonia, and so on. PMD is caused by the pathological changes of oligodendrocyte cell, which end up with hypomyelination disorder. Previous studies have demonstrated PLP1 point mutation affects the survival of oligodendrocytes and the formation of myelin molecular structure by affecting the formation of PLP1/DM20 oligomerization: PLP1 duplication stops oligodendrocyte and myelin development. Recent studies on organelle interaction network (OIN) have further demonstrated the pathogenic mechanism of PLP1 mutations: point mutations impact oligodendrocyte myelination by affecting the trafficking of PLP1 mutants to the plasma membrane. While PLP1 duplication had closer ER-mitochondrion interfaces named mitochondria-associated membranes (MAMs). These changes in both the ER and mitochondria then led to mitochondrial dysfunction. At present, relevant studies have shown that some small molecular compounds or drugs such as cholesterol, piracetam and gene therapy can improve the clinical symptoms of PMD in animals, and their efficacy in PMD patients needs to be further confirmed.
DUAN Ruo-Yu, YAN Hui-Fang, WANG Jing-Min.Reviews and Monographs: Advances in Clinical Features and Pathogenesis of Pelizaeus-Merzbacher Disease[J].,2022,49(11):2115-2129.Export: BibTexEndNote
Enteric glial cells are distributed in the mucosa, submucosa and muscular layer of the digestive tract, and are characterized by extensive heterogeneity and plasticity. The mucosal layer is most close to the intestinal cavity and vulnerable to pathogen and inflammation, thus mucosal homeostasis has attracted much attention. Mucosal enteric glial cells (mEGCs) have complex interactions with intestinal epithelial cells, vascular endothelial cells, immune cells and other nonneuronal cells. From the perspective of structure and function, the intestinal glial cells may be in a central regulatory position. Recent studies have continuously revealed mEGCs subtypes and new functions, indicating that mEGCs has functional changes under pathological conditions. It is critical to understand how mEGCs cause mucosal dysfunction and their role in disease development. This article will summarize the role of mEGCs in maintaining mucosal homeostasis and regulating inflammation.
LI Li, LIU Li-Li.Reviews and Monographs: The Role of Enteric Glia Cells in Intestinal Mucosal Homeostasis and Inflammation[J].,2022,49(11):2130-2135.Export: BibTexEndNote
Megalencephalic leukoencephalopathy (MLC) with subcortical cysts is a degenerative disease of the central nervous system caused by mutations in MLC1 or GlialCAM, characterized with astrocyte swelling and vesicle formation of myelin. MLC/GlialCAM and ClC-2 co-localize at the end feet of astrocytes. Previous studies discovered that MLC1/GlialCAM mutation affects the conductivity of ClC-2 channels, resulting in the imbalance of water and ion homeostasis in astrocytes, while in the GlialCAM homozygous knockout mouse, the phenotype cannot be rescued by crossing with transgenic mice that selectively open ClC-2. Recent study showed that mutated MLC1 promotes the internalization of Connexin43 and reduced the formation of gap junctions at the cell membrane, affected the efficiency of intercellular communication, and interrupted normal glial syncytial function, which led to MLC with astrocyte edema and the vesicle formation of myelin. It indicated that the abnormal function of glial syncytia composed of astrocytes, oligodendrocytes and connexins needs further investigation.
SHI Zhen, WANG Jing-Min.Reviews and Monographs: Research Progress of Pathological Mechanism in Megalencephalic Leukoencephalopathy With Subcortical Cysts[J].,2022,49(11):2136-2141.Export: BibTexEndNote
Spinal cord astrocytoma is a rare malignant tumor of the central nervous system, with unique characteristics in epidemiology, clinical tumor phenotype, molecular genetic markers, and therapeutic research. With the development of surgical techniques and molecular pathology, significant progress has been made in the research and treatment of brain glioma. However, there are only limited advances in the research and treatment of spinal cord astrocytoma. The potential cautions include: (1) it is difficult to carry out research because of the small number of clinical samples; (2) the resistance of the spinal cord to temozolomide, the first-line chemotherapy drug for brain glioma. Therefore, it is urgent to clarify the research status and potential direction of spinal cord astrocytoma to provide clues for improving its clinical efficacy. Here, we comprehensively reviewed the clinical features, pathological classification, molecular characteristics, current treatments, and ongoing studies of spinal cord astrocytoma. In conclusion, the incidence of spinal astrocytoma is less than 1/10 of brain diffuse gliomas. Although spinal cord astrocytoma has younger age than brain hemisphere diffuse glioma, it mainly occurs in adults which is unlike diffuse brain stem gliomas. According to histological phenotype, spinal cord astrocytomas are divided into astrocytoma and glioblastoma. Almost all patients are IDH wild-type, and a high proportion of patients carry the H3 K27M mutation (about 40%). For WHO grade 2/3 patients, maximal surgical resection was associated with a better prognosis, but for WHO grade 4 patients, the prognosis was associated with histological grade, preoperative spinal cord function, and NLR (peripheral blood neutrophil to lymphocyte ratio). Currently, there is no effective treatment for spinal cord astrocytoma other than radiotherapy. Studies on molecular targeted therapy and immunotherapy have brought new hope for spinal cord glioma, but the lack of effective experiment models has limited their progression. Studies in large clinical cohorts, the development of cell and animal experiment models, and the usage of novel study approaches (such as single-cell technology) should be performed as soon as possible on the spinal cord astrocytoma to improve its precision diagnosis and therapy.
The default mode network (DMN) has been reported to be involved in a variety of important cognitive functions and received increasing attention in neuroscience recently. Its dysfunction is also reported to be associated with multiple psychiatric disorders. However, the causal information flow (effective connectivity) within the default mode network remains poorly understood. In this study, we explored the effective connectivity pattern between 4 key DMN brain areas based on a high resolution 7T resting state fMRI dataset using a cutting-edge spectral dynamic causal modelling technique. Results showed that there was a distinct effective connectivity pattern between the DMN nodes. We found medial prefrontal cortex(MPFC) and bilateral inferior parietal cortex(IPC) sent information to the posterior cingulate cortex(PCC), which suggested that the PCC might be a hub region that collected information from other DMN areas. Besides, a causal influence was found from bilateral IPC to MPFC, and from left IPC to right IPC. This work was the first 7T fMRI study that investigated effective connectivity pattern among DMN nodes, which may promote our understandings about the functions of DMN and benefit future research in DMN-related psychiatric disorders.
.Directed Graph of Human Brain’s Default Network: A DCM with 7T fMRI[J]..Export: BibTexEndNote
Objectives This research aimed to investigate the effect and mechanism of miR-125b on the proliferation of gastric cancer cell line MGC803, and to provide the experimental basis for elucidating the molecular mechanism of gastric cancer.Methods 1. The expression of miR-125b was detected by qRT-PCR and in situ hybridization in NGM and GAC tissues. 2. The miR-125b was transfected in gastric cancer MGC-803 cells. The effects of over-expression of miR-125b to the proliferation of gastric cancer MGC-803 cells were observed. 3.The targeting effect of miR-125b on MCL1 gene was analyzed by Targetscan 6.2 software and luciferase reporter gene assay. 4.The interference vector of MCL1 was constructed. The effects of interference expression of MCL1 to the proliferation of gastric cancer MGC-803 cells were observed.Results 1.The expression of miR-125b was low in gastric cancer tissues. The low-expression of miR-125b was positively correlated with the degree of differentiation and prognosis of patients, and negative correlation with TNM staging and lymph node metastasis of gastric cancer (P<0.01) . 2. The proliferation of MGC-803 cells were decreased, and the cell apoptosis rate, cleaved caspase-3 and cleaved PARP cells were increased when the miR-125b was over-expression (P<0.01). 3. MiR-125b binded MCL1-3 'UTR 2613-2620 nucleotide and inhibited the expression of MCL1 mRNA and protein in MGC-803 cells after its over-expression(P<0.01). 4. The proliferation of MGC-803 cells were decreased, and the cell apoptosis rate, cleaved caspase-3 and cleaved PARP cells were increased when the expression of MCL1was silenced (P<0.01).Conclusions The expression of miR-125b was low, and closely related with the differentiation degree of gastric carcinoma, TNM staging, lymph node metastasis and prognosis of patients in gastric cancer tissues. MiR-125b activated Caspase-3 signaling pathway to inhibit the proliferation of MGC803 cells through targeting the expression of MCL1 gene.
Sponsored by：Institute of Biophysics, The Chinese Academy of Sciences; Biophysical Society of ChinaEdited by: Editorial Office of Progress in Biochemistry and BiophysicsPublished by：Editorial Office of PIBBEditor-in-Chief：HE Rong-Qiao Adress：15 Datun Road, Chaoyang District,Beijing 100101,China Telephone：86-10-64888459 Email：firstname.lastname@example.org Journal inclusion：SCI, CA, Scopus, AJ