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Sökning: WFRF:(Benraiss Abdellatif)

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1.
  • Munk, Anne Sofie, et al. (författare)
  • PDGF-B Is Required for Development of the Glymphatic System
  • 2019
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; , s. 3-2969
  • Tidskriftsartikel (refereegranskat)abstract
    • The glymphatic system is a highly polarized cerebrospinal fluid (CSF) transport system that facilitates the clearance of neurotoxic molecules through a brain-wide network of perivascular pathways. Herein we have mapped the development of the glymphatic system in mice. Perivascular CSF transport first emerges in hippocampus in newborn mice, and a mature glymphatic system is established in the cortex at 2 weeks of age. Formation of astrocytic endfeet and polarized expression of aquaporin 4 (AQP4) consistently coincided with the appearance of perivascular CSF transport. Deficiency of platelet-derived growth factor B (PDGF-B) function in the PDGF retention motif knockout mouse line Pdgfb ret/ret suppressed the development of the glymphatic system, whose functions remained suppressed in adulthood compared with wild-type mice. These experiments map the natural development of the glymphatic system in mice and define a critical role of PDGF-B in the development of perivascular CSF transport.
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2.
  • Villanueva, Carlos Benitez, et al. (författare)
  • Astrocytic engagement of the corticostriatal synaptic cleft is disrupted in a mouse model of Huntington s disease
  • 2023
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 120:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Astroglial dysfunction contributes to the pathogenesis of Huntington s disease (HD), and glial replacement can ameliorate the disease course. To establish the topographic relationship of diseased astrocytes to medium spiny neuron (MSN) synapses in HD, we used 2-photon imaging to map the relationship of turboRFP-Tagged striatal astrocytes and rabies-Traced, EGFP-Tagged coupled neuronal pairs in R6/2 HD and wild-Type (WT) mice. The tagged, prospectively identified corticostriatal synapses were then studied by correlated light electron microscopy followed by serial block-face scanning EM, allowing nanometer-scale assessment of synaptic structure in 3D. By this means, we compared the astrocytic engagement of single striatal synapses in HD and WT brains. R6/2 HD astrocytes exhibited constricted domains, with significantly less coverage of mature dendritic spines than WT astrocytes, despite enhanced engagement of immature, thin spines. These data suggest that disease-dependent changes in the astroglial engagement and sequestration of MSN synapses enable the high synaptic and extrasynaptic levels of glutamate and K+ that underlie striatal hyperexcitability in HD. As such, these data suggest that astrocytic structural pathology may causally contribute to the synaptic dysfunction and disease phenotype of those neurodegenerative disorders characterized by network overexcitation.
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