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

• Main Authors: Adriana Lo Castro, Michela Murdocca, Sabina Pucci, Anna Zaratti, Chiara Greggi, Federica Sangiuolo, Virginia Tancredi, Claudio Frank, Giovanna D’Arcangelo
• Format: Article
• Language: English
• Published: MDPI AG 2017-07-01
• Series: International Journal of Molecular Sciences
• Subjects: NPCD; neurodegeneration; i-LTP; LOX-1
• Online Access: https://www.mdpi.com/1422-0067/18/7/1442

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.