Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model
AbstractNiemann-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. View Full-Text
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Lo Castro, A.; Murdocca, M.; Pucci, S.; Zaratti, A.; Greggi, C.; Sangiuolo, F.; Tancredi, V.; Frank, C.; D’Arcangelo, G. Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model. Int. J. Mol. Sci. 2017, 18, 1442.
Lo Castro A, Murdocca M, Pucci S, Zaratti A, Greggi C, Sangiuolo F, Tancredi V, Frank C, D’Arcangelo G. Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model. International Journal of Molecular Sciences. 2017; 18(7):1442.Chicago/Turabian Style
Lo Castro, Adriana; Murdocca, Michela; Pucci, Sabina; Zaratti, Anna; Greggi, Chiara; Sangiuolo, Federica; Tancredi, Virginia; Frank, Claudio; D’Arcangelo, Giovanna. 2017. "Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model." Int. J. Mol. Sci. 18, no. 7: 1442.
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