Critical analysis of translational potential of rodent models of white matter pathology across a wide spectrum of human diseases.

Rodents are the most commonly used laboratory animals in medical research. However, significant evolutionary divergences between humans and rodents, particularly in the complexity of white matter connectome, which are fundamentally shaped by myelin as their major structural component, pose critical challenges in modeling the human neurological diseases. Given the divergences and central roles of myelin in pathology, a thorough reevaluation of the rodent models used in contemporary research is critical, alongside the careful selection, optimization, or de novo development of models that faithfully recapitulate human white matter disorders.

Connexin43 hemichannel blockade turns microglia neuroprotective and mitigates cognitive deficits in a mouse model of amyloidosis.

Alzheimer's disease (AD), the leading cause of senile dementia, lacks effective therapies. While microglia are central to AD pathology, key therapeutic targets remain unclear. Here we identify microglial connexin43 (Cx43) hemichannels as a regulator of microglial reactivity in AD, positioning them as a promising therapeutic target.

Oligodendroglia in Ageing and Age-Dependent Neurodegenerative Diseases.

The central nervous system is susceptible to gradual decline with age, affecting all types of glial cells in the process. Compared to other glial cells, the oligodendroglial lineage is highly vulnerable to ageing and undergoes significant characteristic changes that impact upon its structure and impair its physiological functions. Therefore, the ageing and degeneration of oligodendroglia become major risk factors for neurodegenerative diseases.

Neuroglial Pathophysiology of Leukodystrophies.

Leukodystrophies are a diverse group of inherited diseases characterised by white matter degenerative pathology. Leukodystrophies have a highly heterogeneous genetic background linked mainly to mutations in oligodendrocyte and astrocyte genes and, to lesser extent, microglia. The most prevalent leukodystrophies are caused by mutations in oligodendrocyte genes that encode the essential myelin proteins PLP1 and GalC in Pelizaeus-Merzbacher disease and Krabbe disease, respectively.

Demyelination and Remyelination: General Principles.

Myelinating oligodendrocytes and oligodendrocyte precursor cells (OPCs) make up half the cells in the central nervous system and are affected by and contribute to all neurological diseases. The pathology of myelinating oligodendrocytes is fundamentally characterized by myelin disruption and loss, termed demyelination, whereas that of OPCs is principally defined by remyelination and repair in the form of regeneration of myelinating oligodendrocytes. Demyelination is generally associated with white matter diseases, such as multiple sclerosis, although oligodendroglial pathology is a major factor in most neuropathologies, including Alzheimer's disease, ischaemic injury, and traumatic injury.

Physiology of Oligodendroglia.

Oligodendroglia are highly specialised to myelinate axons and ensure rapid electrical conduction of action potentials in the central nervous system (CNS). The oligodendroglial cell lineage comprises mature myelinating oligodendrocytes, together with oligodendrocyte precursor cells (OPCs) and immature premyelinating oligodendrocytes, their numerical density depending on developmental age. In early embryonic and postnatal development, OPCs and immature oligodendrocytes predominate, whereas in the adult CNS, mature myelinating oligodendrocytes comprise over 90% of the lineage, with OPCs making up a small but significant population (3-9%).

Evolution of Oligodendroglia and Myelin.

The evolution of the nervous system emerged in primaeval animals to coordinate their behaviour then advanced by the division of function between neurones and neuroglia; neurones became dedicated to information processing and neuroglia specialised in homeostatic support. As the nervous system became more complex and neurones extended axonal connections, so periaxonal glial cells arose to provide axonal support. In many invertebrates, periaxonal glia produce multilamellar structures similar in architecture and function to the myelin sheath of vertebrates.

Oligodendroglia and Myelin: Supporting the Connectome.

Oligodendroglia are the only cell lineage of the central nervous system (CNS) responsible for producing myelin. They originate from precursor cells known as oligodendrocyte precursor cells (OPCs), which are born around the ventricular zones of the brain and spinal cord and migrate throughout the developing CNS, and many of them ultimately differentiate into mature myelinating oligodendrocytes. Recent research has shown that OPCs and oligodendrocytes possess distinct characteristics when compared either to other types of glial cells in the CNS or to each other.

Neuroglial Advances: New Roles for Established Players.

Neuroglial cells perform numerous physiological functions and contribute to the pathogenesis of all diseases of the nervous system. Neuroglial neuroprotection defines the resilience of the nervous tissue to exo- and endogenous pathological challenges, while neuroglial defence determines the progression and outcome of neurological disorders. IN this paper, we overview previously unknown but recently discovered roles of various types of neuroglial cells in diverse physiological and pathological processes.

Oligodendroglial precursor cells modulate immune response and early demyelination in a murine model of multiple sclerosis.

Reproducing the pathophysiology of human multiple sclerosis (MS) in animal models is critical to identifying mechanisms triggering demyelination and to developing early intervention strategies. Here, we aimed to model overactivated Wnt (wingless-related integration site) signaling previously shown in postmortem brain tissues of patients with MS by inducing experimental autoimmune encephalomyelitis (EAE) in and mice. These mice have overactivated Wnt signaling in oligodendrocyte precursor cells (OPCs) because of a conditional knockout of the pathway repressor adenomatous polyposis coli (APC).

Oligodendrocyte precursor cells facilitate neuronal lysosome release.

Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes.

BOK-engaged mitophagy alleviates neuropathology in Alzheimer's disease.

Mitochondrial malfunction associated with impaired mitochondrial quality control and self-renewal machinery, known as mitophagy, is an under-appreciated mechanism precipitating synaptic loss and cognitive impairments in Alzheimer's disease. Promoting mitophagy has been shown to improve cognitive function in Alzheimer's disease animals. However, the regulatory mechanism was unclear, which formed the aim of this study.

A New Acquaintance of Oligodendrocyte Precursor Cells in the Central Nervous System.

Oligodendrocyte precursor cells (OPCs) are a heterogeneous multipotent population in the central nervous system (CNS) that appear during embryogenesis and persist as resident cells in the adult brain parenchyma. OPCs could generate oligodendrocytes to participate in myelination. Recent advances have renewed our knowledge of OPC biology by discovering novel markers of oligodendroglial cells, the myelin-independent roles of OPCs, and the regulatory mechanism of OPC development.

Fluoxetine Rescues Excessive Myelin Formation and Psychological Behaviors in a Murine PTSD Model.

Posttraumatic stress disorder (PTSD) is a complex mental disorder notable for traumatic experience memory. Although current first-line treatments are linked with clinically important symptom reduction, a large proportion of patients retained to experience considerable residual symptoms, indicating pathogenic mechanism should be illustrated further. Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation.

Remyelination-oriented clemastine treatment attenuates neuropathies of optic nerve and retina in glaucoma.

As one of the top causes of blindness worldwide, glaucoma leads to diverse optic neuropathies such as degeneration of retinal ganglion cells (RGCs). It is widely accepted that the level of intraocular pressure (IOP) is a major risk factor in human glaucoma, and reduction of IOP level is the principally most well-known method to prevent cell death of RGCs. However, clinical studies show that lowering IOP fails to prevent RGC degeneration in the progression of glaucoma.

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy.

Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO.

Design, Setting, And Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well.

RNF220-mediated K63-linked polyubiquitination stabilizes Olig proteins during oligodendroglial development and myelination.

Maldevelopment of oligodendroglia underlies neural developmental disorders such as leukodystrophy. Precise regulation of the activity of specific transcription factors (TFs) by various posttranslational modifications (PTMs) is required to ensure proper oligodendroglial development and myelination. However, the role of ubiquitination of these TFs during oligodendroglial development is yet unexplored.

Pathological potential of oligodendrocyte precursor cells: terra incognita.

Adult oligodendrocyte precursor cells (aOPCs), transformed from fetal OPCs, are idiosyncratic neuroglia of the central nervous system (CNS) that are distinct in many ways from other glial cells. OPCs have been classically studied in the context of their remyelinating capacity. Recent studies, however, revealed that aOPCs not only contribute to post-lesional remyelination but also play diverse crucial roles in multiple neurological diseases.

Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during development.

Oligodendrocyte precursor cells (OPCs) undergo an extensive and coordinated migration in the developing CNS, using the pre-formed scaffold of developed blood vessels as their physical substrate for migration. While OPC association with vasculature is critical for dispersal, equally important for permitting differentiation and proper myelination of target axons is their appropriate and timely detachment, but regulation of this process remains unclear. Here we demonstrate a correlation between the developmental formation of astrocytic endfeet on vessels and the termination of OPC perivascular migration.

Pathological oligodendrocyte precursor cells revealed in human schizophrenic brains and trigger schizophrenia-like behaviors and synaptic defects in genetic animal model.

Although the link of white matter to pathophysiology of schizophrenia is documented, loss of myelin is not detected in patients at the early stages of the disease, suggesting that pathological evolution of schizophrenia may occur before significant myelin loss. Disrupted-in-schizophrenia-1 (DISC1) protein is highly expressed in oligodendrocyte precursor cells (OPCs) and regulates their maturation. Recently, DISC1-Δ3, a major DISC1 variant that lacks exon 3, has been identified in schizophrenia patients, although its pathological significance remains unknown.

Activation of Wnt/β-catenin pathway mitigates blood-brain barrier dysfunction in Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder that causes age-dependent neurological and cognitive declines. The treatments for Alzheimer's disease pose a significant challenge, because the mechanisms of disease are not being fully understood. Malfunction of the blood-brain barrier is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease, especially at the early stages of the disease.

Evaluation of a prerequisite course of histology implementation for Chinese students of eight-year medical programme: a mixed quantitative survey.

Background: Due to insufficient basic medical knowledge and inappropriate learning strategies, students of 8-year medical programme encountered many obstacles in the initial stage of basic medicine learning. This study was to determine whether a prerequisite course can improve basic medicine learning performance and adjust learning strategies to adapt to basic medicine learning.

Methods: A prerequisite course of histology was constructed by a two-round modified Delphi study.

New insights into the immunologic role of oligodendrocyte lineage cells in demyelination diseases.

Oligodendrocyte lineage cells (OL-lineage cells) are a cell population that are crucial for mammalian central nervous system (CNS) myelination. OL-lineage cells go through developmental stages, initially differentiating into oligodendrocyte precursor cells (OPCs), before becoming immature oligodendrocytes, then mature oligodendrocytes (OLs). While the main function of cell lineage is in myelin formation, and increasing number of studies have turned to explore the immunological characteristics of these cells.

In-utero exposure to air pollution and early-life neural development and cognition.

Air pollution remains one of the major health threats around the world. Compared to adults, foetuses and infants are more vulnerable to the effects of environmental toxins. Maternal exposure to air pollution causes several adverse birth outcomes and may lead to life-long health consequences.