scholarly journals Microglial Neuropilin-1 trans-regulates oligodendrocyte expansion during development and remyelination

2021 ◽  
Author(s):  
Amin Sherafat ◽  
Friederike Pfeiffer ◽  
Alexander Reiss ◽  
William M Wood ◽  
Akiko Nishiyama
Keyword(s):  
White Matter ◽  
Gray Matter ◽  
Integral Membrane Protein ◽  
Dependent Manner ◽  
Oligodendrocyte Precursor Cells ◽  
Neuropilin 1 ◽  
Oligodendrocyte Precursor ◽  
Activity Dependent ◽  
Specific Deletion

NG2 glia or oligodendrocyte precursor cells (OPCs) are distributed throughout the gray and white matter and generate myelinating cells. OPCs in white matter proliferate more than those in gray matter in response to platelet-derived growth factor AA (PDGF AA), despite similar levels of its alpha receptor (PDGFRalpha) on their surface. Here we show that the type 1 integral membrane protein Neuropilin-1 (Nrp1) is expressed not on OPCs but on amoeboid and activated microglia in white but not gray matter in an age- and activity-dependent manner. Microglia-specific deletion of Nrp1 compromised developmental OPC proliferation in white matter as well as OPC expansion and subsequent myelin repair after acute demyelination. Exogenous Nrp1 increased PDGF AA-induced OPC proliferation and PDGFRalpha phosphorylation on dissociated OPCs, most prominently in the presence of suboptimum concentrations of PDGF AA. These findings uncover a novel mechanism of regulating oligodendrocyte lineage cell density that involves trans-activation of PDGFRalpha on OPCs via Nrp1 expressed by adjacent microglia.

scholarly journals Microglial neuropilin-1 promotes oligodendrocyte expansion during development and remyelination by trans-activating platelet-derived growth factor receptor

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amin Sherafat ◽  
Friederike Pfeiffer ◽  
Alexander M. Reiss ◽  
William M. Wood ◽  
Akiko Nishiyama
Keyword(s):  
White Matter ◽  
Growth Factor ◽  
Gray Matter ◽  
Growth Factor Receptor ◽  
Integral Membrane Protein ◽  
Platelet Derived Growth Factor ◽  
Dependent Manner ◽  
Neuropilin 1 ◽  
Activity Dependent

AbstractNerve-glia (NG2) glia or oligodendrocyte precursor cells (OPCs) are distributed throughout the gray and white matter and generate myelinating cells. OPCs in white matter proliferate more than those in gray matter in response to platelet-derived growth factor AA (PDGF AA), despite similar levels of its alpha receptor (PDGFRα) on their surface. Here we show that the type 1 integral membrane protein neuropilin-1 (Nrp1) is expressed not on OPCs but on amoeboid and activated microglia in white but not gray matter in an age- and activity-dependent manner. Microglia-specific deletion of Nrp1 compromised developmental OPC proliferation in white matter as well as OPC expansion and subsequent myelin repair after acute demyelination. Exogenous Nrp1 increased PDGF AA-induced OPC proliferation and PDGFRα phosphorylation on dissociated OPCs, most prominently in the presence of suboptimum concentrations of PDGF AA. These findings uncover a mechanism of regulating oligodendrocyte lineage cell density that involves trans-activation of PDGFRα on OPCs via Nrp1 expressed by adjacent microglia.

Abstract TMP30: M2 Microglia Derived Exosomes Promote White Matter Repair and Long-Term Functional Recovery After Focal Cerebral Ischemia in Mice

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yongfang Li ◽  
Longlong Luo ◽  
Zhijun Zhang ◽  
Yaohui Tang ◽  
Guo-Yuan Yang
Keyword(s):  
White Matter ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor Cell ◽  
M2 Microglia ◽  
Oligodendrocyte Precursor ◽  
White Matter Repair ◽  
Exosomal Mirna

Objectives: White matter injury aggravates neurological and cognitive impairment in experimental ischemic stroke. M2 microglia promote oligodendrocyte precursor cells survival and differentiation, and further enhance white matter repair. However, the molecular mechanism is unclear. Here, we explored the effect and mechanism of M2 microglia-derived exosomes on white matter repair after focal cerebral ischemia in mice. Methods: Microglia BV2 cells were polarized to M2 phenotype by IL-4 stimulation. Exosomes were isolated from M2 microglia (M2-Exo) and unstimulated microglia as a control (M0-Exo). M2-Exo and M0-Exo (100 μg) were intravenously injected after 90-minute middle cerebral artery occlusion in mice (n=72). Brain atrophy volume and neuro behavioral outcomes were examined in 28 days following focal cerebral ischemia. Oligodendrocyte precursor cells survival, differentiation and white matter integrity were evaluated. Exosomal miRNA and target gene were further examined to explore molecular mechanism. Results: M2-Exo treatment promoted sensorimotor and memory function recovery ( p <0.05), and further reduced brain atrophy compared to the M0-Exo control group ( p <0.001). Immunostaining showed that M2-Exo increased the number of BrdU + /Pdgfr-α + and BrdU + /adenomatous polyposis coli + cells, enhanced myelin basic protein fluorescence-intensity compared to the control ( p <0.05). M2-Exo increased oligodendrocyte precursor cell survival under OGD in vi tro , ( p <0.05) and differentiation ( p <0.05). Exosomal miRNA sequencing and PCR identified that miR-23a-5p was enriched in M2-Exo. Conclusion: Our results showed that M2-Exo treatment enhanced oligodendrocyte precursor cell survival and differentiation, further promoted white matter repair and long-term functional recovery, suggesting that M2-Exo is a novel therapeutic strategy for the white matter repair after ischemic brain injury.

scholarly journals White Matter and Neuroprotection in Alzheimer’s Dementia

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 503 ◽  
Author(s):  
Luca Lorenzini ◽  
Mercedes Fernandez ◽  
Vito Antonio Baldassarro ◽  
Andrea Bighinati ◽  
Alessandro Giuliani ◽  
...  
Keyword(s):  
White Matter ◽  
Alzheimer’S Dementia ◽  
Oligodendrocyte Precursor Cells ◽  
Resonance Imaging ◽  
Alzheimer's Dementia ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
Main Component ◽  
Preclinical And Clinical Studies

Myelin is the main component of the white matter of the central nervous system (CNS), allowing the proper electrical function of the neurons by ensheathing and insulating the axons. The extensive use of magnetic resonance imaging has highlighted the white matter alterations in Alzheimer’s dementia (AD) and other neurodegenerative diseases, alterations which are early, extended, and regionally selective. Given that the white matter turnover is considerable in the adulthood, and that myelin repair is currently recognized as being the only true reparative capability of the mature CNS, oligodendrocyte precursor cells (OPCs), the cells that differentiate in oligodendrocyte, responsible for myelin formation and repair, are regarded as a potential target for neuroprotection. In this review, several aspects of the OPC biology are reviewed. The histology and functional role of OPCs in the neurovascular-neuroglial unit as described in preclinical and clinical studies on AD is discussed, such as the OPC vulnerability to hypoxia-ischemia, neuroinflammation, and amyloid deposition. Finally, the position of OPCs in drug discovery strategies for dementia is discussed.

scholarly journals Brain imaging in myotonic dystrophy type 1

Neurology ◽  
2017 ◽  
Vol 89 (9) ◽  
pp. 960-969 ◽  
Author(s):  
Kees Okkersen ◽  
Darren G. Monckton ◽  
Nhu Le ◽  
Anil M. Tuladhar ◽  
Joost Raaphorst ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Imaging ◽  
Longitudinal Studies ◽  
Myotonic Dystrophy ◽  
Gray Matter ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Pooled Prevalence ◽  
The Brain

Objective:To systematically review brain imaging studies in myotonic dystrophy type 1 (DM1).Methods:We searched Embase (index period 1974–2016) and MEDLINE (index period 1946–2016) for studies in patients with DM1 using MRI, magnetic resonance spectroscopy (MRS), functional MRI (fMRI), CT, ultrasound, PET, or SPECT. From 81 studies, we extracted clinical characteristics, primary outcomes, clinical-genetic correlations, and information on potential risk of bias. Results were summarized and pooled prevalence of imaging abnormalities was calculated, where possible.Results:In DM1, various imaging changes are widely dispersed throughout the brain, with apparently little anatomical specificity. We found general atrophy and widespread gray matter volume reductions in all 4 cortical lobes, the basal ganglia, and cerebellum. The pooled prevalence of white matter hyperintensities is 70% (95% CI 64–77), compared with 6% (95% CI 3–12) in unaffected controls. DTI shows increased mean diffusivity in all 4 lobes and reduced fractional anisotropy in virtually all major association, projection, and commissural white matter tracts. Functional studies demonstrate reduced glucose uptake and cerebral perfusion in frontal, parietal, and temporal lobes, and abnormal fMRI connectivity patterns that correlate with personality traits. There is significant between-study heterogeneity in terms of imaging methods, which together with the established clinical variability of DM1 may explain divergent results. Longitudinal studies are remarkably scarce.Conclusions:DM1 brains show widespread white and gray matter involvement throughout the brain, which is supported by abnormal resting-state network, PET/SPECT, and MRS parameters. Longitudinal studies evaluating spatiotemporal imaging changes are essential.

scholarly journals Oligodendrocyte Precursor Cells Modulate the Neuronal Network by Activity-Dependent Ectodomain Cleavage of Glial NG2

PLoS Biology ◽  
2014 ◽  
Vol 12 (11) ◽  
pp. e1001993 ◽  
Author(s):  
Dominik Sakry ◽  
Angela Neitz ◽  
Jeet Singh ◽  
Renato Frischknecht ◽  
Daniele Marongiu ◽  
...  
Keyword(s):  
Neuronal Network ◽  
Precursor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor ◽  
Activity Dependent

Oligodendrocyte precursor cell transplantation promotes angiogenesis and remyelination via Wnt/β-catenin pathway in a mouse model of middle cerebral artery occlusion

2021 ◽  
pp. 0271678X2110653
Author(s):  
Li-Ping Wang ◽  
Jiaji Pan ◽  
Yongfang Li ◽  
Jieli Geng ◽  
Chang Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Cell Transplantation ◽  
Artery Occlusion ◽  
Precursor Cells ◽  
Precursor Cell ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor Cell ◽  
Oligodendrocyte Precursor ◽  
Cerebral Artery Occlusion

White matter injury is a critical pathological characteristic during ischemic stroke. Oligodendrocyte precursor cells participate in white matter repairing and remodeling during ischemic brain injury. Since oligodendrocyte precursor cells could promote Wnt-dependent angiogenesis and migrate along vasculature for the myelination during the development in the central nervous system, we explore whether exogenous oligodendrocyte precursor cell transplantation promotes angiogenesis and remyelination after middle cerebral artery occlusion in mice. Here, oligodendrocyte precursor cell transplantation improved motor and cognitive function, and alleviated brain atrophy. Furthermore, oligodendrocyte precursor cell transplantation promoted functional angiogenesis, and increased myelin basic protein expression after ischemic stroke. The further study suggested that white matter repairing after oligodendrocyte precursor cell transplantation depended on angiogenesis induced by Wnt/β-catenin signal pathway. Our results demonstrated a novel pathway that Wnt7a from oligodendrocyte precursor cells acting on endothelial β-catenin promoted angiogenesis and improved neurobehavioral outcomes, which facilitated white matter repair and remodeling during ischemic stroke.

Regulation of L-type Ca++ currents and process morphology in white matter oligodendrocyte precursor cells by golli-myelin proteins

Glia ◽  
2010 ◽  
Vol 58 (11) ◽  
pp. 1292-1303 ◽  
Author(s):  
Daniel Fulton ◽  
Pablo M. Paez ◽  
Robin Fisher ◽  
Vance Handley ◽  
Christopher S. Colwell ◽  
...  
Keyword(s):  
White Matter ◽  
Precursor Cells ◽  
Myelin Proteins ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor ◽  
Ca Currents

scholarly journals Shaping of Regional Differences in Oligodendrocyte Dynamics by Regional Heterogeneity of the Pericellular Microenvironment

2021 ◽  
Vol 15 ◽  
Author(s):  
Amin Sherafat ◽  
Friederike Pfeiffer ◽  
Akiko Nishiyama
Keyword(s):  
White Matter ◽  
Gray Matter ◽  
Regional Differences ◽  
Phenotypic Variability ◽  
Adult Brain ◽  
Normal Brain ◽  
Regional Heterogeneity ◽  
Myelin Sheaths ◽  
Oligodendrocyte Precursor ◽  
Functional States

Oligodendrocyte precursor cells (OPCs) are glial cells that differentiate into mature oligodendrocytes (OLs) to generate new myelin sheaths. While OPCs are distributed uniformly throughout the gray and white matter in the developing and adult brain, those in white matter proliferate and differentiate into oligodendrocytes at a greater rate than those in gray matter. There is currently lack of evidence to suggest that OPCs comprise genetically and transcriptionally distinct subtypes. Rather, the emerging view is that they exist in different cell and functional states, depending on their location and age. Contrary to the normal brain, demyelinated lesions in the gray matter of multiple sclerosis brains contain more OPCs and OLs and are remyelinated more robustly than those in white matter. The differences in the dynamic behavior of OL lineage cells are likely to be influenced by their microenvironment. There are regional differences in astrocytes, microglia, the vasculature, and the composition of the extracellular matrix (ECM). We will discuss how the regional differences in these elements surrounding OPCs might shape their phenotypic variability in normal and demyelinated states.

scholarly journals An activity-dependent local transport regulation via degradation and synthesis of KIF17 underlying cognitive flexibility

2020 ◽  
Vol 6 (51) ◽  
pp. eabc8355
Author(s):  
Suguru Iwata ◽  
Momo Morikawa ◽  
Yosuke Takei ◽  
Nobutaka Hirokawa
Keyword(s):  
Cognitive Flexibility ◽  
Molecular Motor ◽  
Fear Memory ◽  
Dependent Manner ◽  
Weight Changes ◽  
Regulatory Processes ◽  
Aspartate Receptor ◽  
Local Transport ◽  
Activity Dependent ◽  
Specific Deletion

Synaptic weight changes among postsynaptic densities within a single dendrite are regulated by the balance between localized protein degradation and synthesis. However, the molecular mechanism via these opposing regulatory processes is still elusive. Here, we showed that the molecular motor KIF17 was locally degraded and synthesized in an N-methyl-d-aspartate receptor (NMDAR)–mediated activity–dependent manner. Accompanied by the degradation of KIF17, its transport was temporarily dampened in dendrites. We also observed that activity-dependent local KIF17 synthesis driven by its 3′ untranslated region (3′UTR) occurred at dendritic shafts, and the newly synthesized KIF17 moved along the dendrites. Furthermore, hippocampus-specific deletion of Kif17 3′UTR disrupted KIF17 synthesis induced by fear memory retrieval, leading to impairment in extinction of fear memory. These results indicate that the regulation of the KIF17 transport is driven by the single dendrite–restricted cycle of degradation and synthesis that underlies cognitive flexibility.

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