Early hippocampal i-LTP and LOX-1 overexpression induced by anoxia: A potential role in neurodegeneration in NPC mouse model

Adriana Lo Castro, Michela Murdocca, Sabina Pucci, Anna Zaratti, Chiara Greggi, Federica Sangiuolo, Virginia Tancredi, Claudio Frank, Giovanna D’Arcangelo

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number1442
JournalInternational Journal of Molecular Sciences
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 5 2017

Fingerprint

Oxidized LDL Receptors
anoxia
Lipoproteins
Long-Term Potentiation
LDL Lipoproteins
mice
Glucose
Proteins
Oxygen
Oxidative stress
Cholesterol
Neurology
Biomarkers
Type C Niemann-Pick Disease
Class E Scavenger Receptors
deprivation
lipoproteins
Oxidation
Kinetics
glucose

Keywords

  • I-LTP
  • LOX-1
  • Neurodegeneration
  • NPCD

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Early hippocampal i-LTP and LOX-1 overexpression induced by anoxia : A potential role in neurodegeneration in NPC mouse model. / Castro, Adriana Lo; Murdocca, Michela; Pucci, Sabina; Zaratti, Anna; Greggi, Chiara; Sangiuolo, Federica; Tancredi, Virginia; Frank, Claudio; D’Arcangelo, Giovanna.

In: International Journal of Molecular Sciences, Vol. 18, No. 7, 1442, 05.07.2017.

Research output: Contribution to journalArticle

Castro, Adriana Lo ; Murdocca, Michela ; Pucci, Sabina ; Zaratti, Anna ; Greggi, Chiara ; Sangiuolo, Federica ; Tancredi, Virginia ; Frank, Claudio ; D’Arcangelo, Giovanna. / Early hippocampal i-LTP and LOX-1 overexpression induced by anoxia : A potential role in neurodegeneration in NPC mouse model. In: International Journal of Molecular Sciences. 2017 ; Vol. 18, No. 7.
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AU - Zaratti, Anna

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