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 Vanishing White Matter Disease Expression of Truncated EIF2B5 Activates Induced Stress Response

2020 ◽  
Author(s):  
Matthew D. Keefe ◽  
Haille E. Soderholm ◽  
Hung-Yu Shih ◽  
Tamara J. Stevenson ◽  
Kathryn A. Glaittli ◽  
...  
Keyword(s):  
White Matter ◽  
Motor Behavior ◽  
Somatic Growth ◽  
Initiation Factor ◽  
White Matter Disease ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
Vanishing White Matter Disease ◽  
Development And Validation ◽  
Vanishing White Matter

AbstractVanishing White Matter disease (VWM) is a severe leukodystrophy of the central nervous system caused by mutations in subunits of the eukaryotic initiation factor 2B complex (eIF2B). Current models only partially recapitulate key disease features, and pathophysiology is poorly understood. Through development and validation of zebrafish (Danio rerio) models of VWM, we demonstrate that zebrafish eif2b mutants phenocopy VWM, including impaired somatic growth, early lethality, impaired myelination, loss of oligodendrocyte precursor cells, increased apoptosis in the CNS, and impaired motor swimming behavior. Expression of human EIF2B2 in the zebrafish eif2b2 mutant rescues lethality and CNS apoptosis, demonstrating conservation of function between zebrafish and human. In the mutants, intron 12 retention leads to expression of a truncated eif2b5 transcript. Expression of the truncated eif2b5 in wild-type larva impairs motor behavior and activates the ISR, suggesting that a feed-forward mechanism in VWM is a significant component of disease pathophysiology.

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.

P3-096: Role of copper in Alzheimer's dementia: A controlled study

2015 ◽  
Vol 11 (7S_Part_14) ◽  
pp. P656-P657
Author(s):  
Siddhesh Sanjeev Shere ◽  
Srikala Bharath ◽  
Sarada Subramanian ◽  
Meera Purushottam
Keyword(s):  
Alzheimer’S Dementia ◽  
Controlled Study ◽  
Alzheimer's Dementia
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