Activation of glutamatergic neurons in the somatosensory cortex promotes remyelination in ischemic vascular dementia

Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however no effective treatments are available. Here, based on magnetic resonance imaging studies of patients with white matter damage, we found that this damage is associated with disorganized cortical structure. In a mouse model, optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell (OPC) proliferation, remyelination in the corpus callosum, and recovery of cognitive ability after cerebral hypoperfusion. The therapeutic effect of such stimulation was restricted to the upper layers of the cortex, but also spanned a wide time window after ischemia. Mechanistically, enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons. Additionally, skin stroking, an easier method to translate into clinical practice, activated the somatosensory cortex, thereby promoting OPC proliferation, remyelination and cognitive recovery following cerebral hypoperfusion. In summary, we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion. It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.

• Publication year

  2022

• Venue

  Fundamental Research

• Publication date

  2022-08-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.fmre.2022.08.007PMID 38933843PMCID 11197523
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Triptolide protects against white matter injury induced by chronic cerebral hypoperfusion in mice

  2021cited by this paper
• TAPP1 Represses the Differentiation of Oligodendrocyte and its Deficiency Accelerates Myelin Regeneration after Demyelinating Injuries

  2020cited by this paper
• Tetradecyl 2,3-dihydroxybenzoate alleviates oligodendrocyte damage following chronic cerebral hypoperfusion through IGF-1 receptor.

  2020cited by this paper
• Glutamatergic signaling between neurons and oligodendrocyte lineage cells: Is it synaptic or non‐synaptic?

  2019cited by this paper
• Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner

  2018cited by this paper
• Better Correlation of Cognitive Function to White Matter Integrity than to Blood Supply in Subjects with Leukoaraiosis

  2017cited by this paper
• Interleukin-1β impedes oligodendrocyte progenitor cell recruitment and white matter repair following chronic cerebral hypoperfusion.

  2017cited by this paper
• Dynamic Modulation of Myelination in Response to Visual Stimuli Alters Optic Nerve Conduction Velocity

  2016influential reference
• Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion

  2015cited by this paper
• White matter hyperintensities, cognitive impairment and dementia: an update

  2015cited by this paper
• Glia Disease and Repair-Remyelination.

  2015cited by this paper
• Neuronal Activity Promotes Oligodendrogenesis and Adaptive Myelination in the Mammalian Brain

  2014cited by this paper
• Adult Neural Precursor Cells from the Subventricular Zone Contribute Significantly to Oligodendrocyte Regeneration and Remyelination

  2014cited by this paper
• Identification of Bax-interacting proteins in oligodendrocyte progenitors during glutamate excitotoxicity and perinatal hypoxia–ischemia

  2013cited by this paper
• Oligodendroglia and neurotrophic factors in neurodegeneration

  2013cited by this paper
• Polydendrocytes in development and myelin repair

  2013cited by this paper
• Protective Effect of Carnosine on Subcortical Ischemic Vascular Dementia in Mice

  2012cited by this paper
• Pharmacological prevention and treatment of vascular dementia: approaches and perspectives.

  2012cited by this paper
• Development, specification, and diversity of callosal projection neurons.

  2011cited by this paper
• CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination.

  2010cited by this paper
• The adhesive removal test: a sensitive method to assess sensorimotor deficits in mice

  2009cited by this paper
• Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors.

  2008cited by this paper
• Remyelination in the CNS: from biology to therapy

  2008cited by this paper
• Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter

  2008cited by this paper
• Neuronal subtype specification in the cerebral cortex

  2007cited by this paper
• Vascular cognitive impairment

  2006cited by this paper
• Axonal damage and demyelination in the white matter after chronic cerebral hypoperfusion in the rat.

  2002cited by this paper
• TNFα promotes proliferation of oligodendrocyte progenitors and remyelination

  2001cited by this paper
• TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination.

  2001cited by this paper
• Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus

  2000cited by this paper
• Oligodendrocyte progenitor cell proliferation and lineage progression are regulated by glutamate receptor-mediated K+ channel block

  1996cited by this paper
• Induction of myelination in the central nervous system by electrical activity.

  1996cited by this paper
• MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging.

  1987cited by this paper
• Developmental Cognitive Neuroscience Neural correlates of gentle skin stroking in early infancy

  year unknowncited by this paper

• Semaglutide to remodel mitochondrial dynamics and mitophagy balance for vascular dementia therapy

  2025cites this paper
• Vascular dementia increases levels of methylenetetrahydrofolate reductase and cystathionine β-synthase in female patients and changes gene expression of acetylcholine and glutamate clathrin-sculpted transport vesicles

  2025cites this paper
• Low-intensity transcranial ultrasound stimulation improves memory in vascular dementia by enhancing neuronal activity and promoting spine formation

  2024cites this paper
• Neuronal activity and remyelination: new insights into the molecular mechanisms and therapeutic advancements

  2023influential citation