Can Enhancing Neuronal Activity Improve Myelin Repair in Multiple Sclerosis?

Maas, Dorien A.; Angulo, Marı́a Cecilia

doi:10.3389/fncel.2021.645240

Cited by 18 publications

(17 citation statements)

References 76 publications

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“…It has been shown by work from several labs that neuronal activity can increase myelination; this is reviewed elsewhere ( Maas and Angulo, 2021 ). Briefly, increasing neuronal activity using chemogenetics leads to increase in OPC proliferation and differentiation of OPCs, as well as increasing the probability of an axon being myelinated, and resulting in thicker myelin on stimulated axons ( Gibson et al, 2014 ; Mitew et al, 2018 ).…”

Section: Direct Synaptic Transmissionmentioning

confidence: 99%

Neuron to Oligodendrocyte Precursor Cell Synapses: Protagonists in Oligodendrocyte Development and Myelination, and Targets for Therapeutics

2022

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The development of neuronal circuitry required for cognition, complex motor behaviors, and sensory integration requires myelination. The role of glial cells such as astrocytes and microglia in shaping synapses and circuits have been covered in other reviews in this journal and elsewhere. This review summarizes the role of another glial cell type, oligodendrocytes, in shaping synapse formation, neuronal circuit development, and myelination in both normal development and in demyelinating disease. Oligodendrocytes ensheath and insulate neuronal axons with myelin, and this facilitates fast conduction of electrical nerve impulses via saltatory conduction. Oligodendrocytes also proliferate during postnatal development, and defects in their maturation have been linked to abnormal myelination. Myelination also regulates the timing of activity in neural circuits and is important for maintaining the health of axons and providing nutritional support. Recent studies have shown that dysfunction in oligodendrocyte development and in myelination can contribute to defects in neuronal synapse formation and circuit development. We discuss glutamatergic and GABAergic receptors and voltage gated ion channel expression and function in oligodendrocyte development and myelination. We explain the role of excitatory and inhibitory neurotransmission on oligodendrocyte proliferation, migration, differentiation, and myelination. We then focus on how our understanding of the synaptic connectivity between neurons and OPCs can inform future therapeutics in demyelinating disease, and discuss gaps in the literature that would inform new therapies for remyelination.

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Section: Direct Synaptic Transmissionmentioning

confidence: 99%

Neuron to Oligodendrocyte Precursor Cell Synapses: Protagonists in Oligodendrocyte Development and Myelination, and Targets for Therapeutics

2022

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“…It has recently been suggested that OPCs are able to communicate with surrounding neurons through non-synaptic junctions during OPC maturation to myelinating OLs [ 164 ]. It is known that growth factors are involved in this axon-OL crosstalk; in addition, OPCs receive excitatory and inhibitory synaptic inputs mediated, respectively, by glutamate and GABA [ 27 , 28 , 165 ], thus suggesting that these neurotransmitters may also control OL development and myelination [ 166 , 167 , 168 ]. Co-transmitters and neuromodulators like ATP and adenosine are also important mediators for oligodendrogliogenesis [ 169 , 170 ].…”

Section: Neurotransmitters In Oligodendroglial Cells and Myelinationmentioning

confidence: 99%

Ion Channels as New Attractive Targets to Improve Re-Myelination Processes in the Brain

Cherchi

Bulli

Venturini

et al. 2021

IJMS

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Multiple sclerosis (MS) is the most demyelinating disease of the central nervous system (CNS) characterized by neuroinflammation. Oligodendrocyte progenitor cells (OPCs) are cycling cells in the developing and adult CNS that, under demyelinating conditions, migrate to the site of lesions and differentiate into mature oligodendrocytes to remyelinate damaged axons. However, this process fails during disease chronicization due to impaired OPC differentiation. Moreover, OPCs are crucial players in neuro-glial communication as they receive synaptic inputs from neurons and express ion channels and neurotransmitter/neuromodulator receptors that control their maturation. Ion channels are recognized as attractive therapeutic targets, and indeed ligand-gated and voltage-gated channels can both be found among the top five pharmaceutical target groups of FDA-approved agents. Their modulation ameliorates some of the symptoms of MS and improves the outcome of related animal models. However, the exact mechanism of action of ion-channel targeting compounds is often still unclear due to the wide expression of these channels on neurons, glia, and infiltrating immune cells. The present review summarizes recent findings in the field to get further insights into physio-pathophysiological processes and possible therapeutic mechanisms of drug actions.

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“…Neuronal activity-dependent myelination is the well-known process by which electrical activity of axons instructs ODCs to myelinate these active axons, thereby increasing their conduction velocity [ 27 ]. The mechanism underlying this phenomenon is not clearly understood; however, leakage of axonal components, such as potassium and glutamate, from unmyelinated sites of electrically active axons is considered to locally trigger a series of cellular responses towards myelination [ 27 , 28 ]. Even if a patient is completely paralyzed due to severe demyelination, action potentials generated by the one’s will to move his/her body might reach the unmyelinated sites and provoke the myelin repairing processes.…”

Section: Discussionmentioning

confidence: 99%

A 44-Year-Old Alcohol-Dependent Man Who Recovered from Central Pontine Myelinolysis with Supportive Physical Therapy

Tobiume¹,

Iha²,

Miyahira³

et al. 2022

Am J Case Rep

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Patient: Male, 44-year-old Final Diagnosis: Central pontine myelinolysis Symptoms: Bulbar paralysis • locked-in syndrome • tetraplegia Medication: — Clinical Procedure: Brain MRI Specialty: Neurology • Rehabilitation Objective: Unusual clinical course Background: Central pontine myelinolysis (CPM) includes symmetric demyelination of the central pons. CPM is a rare neurological disorder that generally develops after rapid correction of hyponatremia in individuals having underlying conditions, such as malnutrition, alcoholism, and severe burns. It can cause severe long-term disabilities. However, there is currently no pharmacotherapy capable of promoting remyelination, a process crucial for recovery from CPM. We present the case of a patient with alcoholism and malnutrition-related CPM, which developed following rapid correction of hyponatremia but then improved remarkably with supportive physical therapy. Case Report: A 44-year-old alcoholic and malnourished man was admitted to an emergency hospital for disorientation due to overdrinking, but later developed bulbar palsy after hyponatremia was unexpectedly, but rapidly, corrected. Axial scans of the diffusion-weighted brain MRI revealed a characteristic lesion known as a piglet sign in the central pons. Based on his underlying conditions, present episode of sodium correction, and MRI finding, the patient was diagnosed as having CPM, which progressively worsened, resulting in locked-in syndrome after 12 days. The patient was then transferred to a long-term care unit and received simple motion exercise daily, but no specific medication. His symptoms gradually improved, achieving discontinuation of tube feeding on day 21, independent walking on day 110, and discharge after 6 months. Conclusions: This report highlights the importance of physical therapy, the potential of which is often underestimated despite its broad benefits for human health, as a readily applicable intervention for patients with CPM. Further understanding of mechanisms underlying exercise-induced myelination should contribute to establishing novel therapies for a wide spectrum of brain disorders.

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Can Enhancing Neuronal Activity Improve Myelin Repair in Multiple Sclerosis?

Cited by 18 publications

References 76 publications

Neuron to Oligodendrocyte Precursor Cell Synapses: Protagonists in Oligodendrocyte Development and Myelination, and Targets for Therapeutics

Neuron to Oligodendrocyte Precursor Cell Synapses: Protagonists in Oligodendrocyte Development and Myelination, and Targets for Therapeutics

Ion Channels as New Attractive Targets to Improve Re-Myelination Processes in the Brain

A 44-Year-Old Alcohol-Dependent Man Who Recovered from Central Pontine Myelinolysis with Supportive Physical Therapy

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