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.

Castro, A.L., Murdocca, M., Pucci, S., Zaratti, A., Greggi, C., Sangiuolo, F., et al. (2017). 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, 18(7) [10.3390/ijms18071442].

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

Murdocca M.;Pucci S.;ZARATTI, ANNA;Sangiuolo F.;Tancredi V.;FRANK, CLAUDIO;D'arcangelo G.
2017

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/09
Settore BIO/11
English
LOX-1; NPCD; i-LTP; neurodegeneration
Castro, A.L., Murdocca, M., Pucci, S., Zaratti, A., Greggi, C., Sangiuolo, F., et al. (2017). 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, 18(7) [10.3390/ijms18071442].
Castro, Al; Murdocca, M; Pucci, S; Zaratti, A; Greggi, C; Sangiuolo, F; Tancredi, V; Frank, C; D'Arcangelo, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/190144
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