Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • معلومة اضافية
    • بيانات النشر:
      MDPI AG, 2017.
    • الموضوع:
      2017
    • نبذة مختصرة :
      Niemann-Pick type C disease (NPCD) is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endo-lysosomal compartment of cells. In the central nervous system, hypoxic insults could result in low-density lipoprotein (LDL) oxidation and Lectin-like oxidized LDL receptor-1 (LOX-1) induction, leading to a pathological hippocampal response, namely, ischemic long-term potentiation (i-LTP). These events may correlate with the progressive neural loss observed in NPCD. To test these hypotheses, hippocampal slices from Wild Type (WT) and NPC1−/− mice were prepared, and field potential in the CA1 region was analyzed during transient oxygen/glucose deprivation (OGD). Moreover, LOX-1 expression was evaluated by RT-qPCR, immunocytochemical, and Western blot analyses before and after an anoxic episode. Our results demonstrate the development of a precocious i-LTP in NPC1−/− mice during OGD application. We also observed a higher expression of LOX-1 transcript and protein in NPC1−/− mice with respect to WT mice; after anoxic damage to LOX-1 expression, a further increase in both NPC1−/− and WT mice was observed, although the protein expression seems to be delayed, suggesting a different kinetic of induction. These data clearly suggest an elevated susceptibility to neurodegeneration in NPC1−/− mice due to oxidative stress. The observed up-regulation of LOX-1 in the hippocampus of NPC1−/− mice may also open a new scenario in which new biomarkers can be identified.
    • ISSN:
      1422-0067
    • Rights:
      OPEN
    • الرقم المعرف:
      edsair.doi.dedup.....1c32858eba892c8328ac85d8495839bd