Related Experiment Video
Updated: May 23, 2026
09:41
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Gap junction pathology in multiple sclerosis lesions and normal-appearing white matter
Kyriaki Markoullis1, Irene Sargiannidou, Natasa Schiza
1Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus.
Acta Neuropathologica
|April 10, 2012
Summary
Oligodendrocyte gap junctions (GJs) are disrupted in multiple sclerosis (MS) lesions and normal-appearing white matter. This disruption affects myelin and hinders remyelination by oligodendrocyte precursor cells (OPCs).
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Oligodendrocyte gap junctions (GJs) are crucial for central nervous system myelination.
- The role of these GJs in multiple sclerosis (MS) pathology is not well understood.
Purpose of the Study:
- To investigate alterations in oligodendrocyte and astrocyte GJs within MS lesions and normal-appearing white matter (NAWM).
Main Methods:
- Analysis of post-mortem brain samples from MS patients and controls.
- Neuropathological characterization of lesions using Luxol Fast Blue, MOG, and Iba1 immunostaining.
- Quantitative analysis of connexin (Cx) expression (Cx32, Cx47, Cx43) via immunoblot and real-time PCR.
- Quantification of GJ plaque formation using immunohistochemistry.
Main Results:
- Reduced Cx32 and Cx47 GJ plaques and protein levels in MS lesions compared to controls.
- Increased Cx43 expression in MS lesions, associated with astrogliosis.
- Significant reduction of Cx32 in NAWM myelinated fibers and increased Cx47 in oligodendrocyte precursor cells (OPCs).
- Limited astrocyte-oligodendrocyte GJ connectivity in OPCs within NAWM.
Conclusions:
- Oligodendrocyte GJs are compromised in both MS lesions and NAWM, potentially impairing myelin integrity and function.
- Defective GJ connectivity in recruited OPCs may impede remyelination efforts in the context of chronic inflammation and astrogliosis.
Related Concept Videos
01:19Multiple Sclerosis l: Introduction
Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
01:25Nervous Tissue: Myelin
The myelin sheath is a multilayered lipid and protein covering that insulates the axon of a neuron, enhancing the speed of nerve impulse conduction. Axons without this sheath are referred to as unmyelinated. Two types of neuroglia, Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS) are responsible for producing myelin sheaths.
Schwann cells begin to form myelin sheaths around axons during fetal development. They wrap around a small...
Schwann cells begin to form myelin sheaths around axons during fetal development. They wrap around a small...
01:37Gap Junctions
Multicellular organisms employ a variety of ways for cells to communicate with each other. Gap junctions are specialized proteins that form pores between neighboring cells in animals, connecting the cytoplasm between the two, and allowing for the exchange of molecules and ions. They are found in a wide range of invertebrate and vertebrate species, mediate numerous functions including cell differentiation and development, and are associated with numerous human diseases, including cardiac and...
01:27Gap Junctions
The cytoplasm of adjacent animal cells can exchange small molecules, ions, and secondary messengers via the communication channels which form the gap junctions. These junctions comprise a few hundred to thousands of molecular channels, each made of two halves, called the connexon hemichannel. A connexon is a hexamer of six transmembrane connexin proteins, which assemble radially, thus forming a pore or channel in the center. One connexon hemichannel docks with a corresponding connexon on the...
01:23Alzheimer Disease ll: Pathophysiology
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
01:22Myasthenia Gravis ll: Pathophysiology
The disease process of myasthenia gravis begins at the neuromuscular junction, where antibodies attack key proteins needed for muscle activation. This immune reaction weakens signal transmission, leading to the characteristic muscle fatigue and weakness that define the condition.Immune-Mediated DamageIn most individuals, antibodies target acetylcholine receptors (AChRs) on the postsynaptic membrane of muscle cells. By blocking acetylcholine binding, these antibodies prevent the nerve signal...