Impact of manganese on primary hippocampal neurons from rodents

Autor: Yasmina Saoudi, Sylvain Bohic, Annie Andrieux, Mariano Bisbal, Jacques Brocard, Emmanuel L. Barbier, Alexia Daoust, Murielle Salomé, Nora Collomb, Cécile Batandier
Rok vydání: 2014
Předmět:
Zdroj: Hippocampus. 24:598-610
ISSN: 1050-9631
Popis: Manganese-enhanced magnetic resonance imaging (MEMRI) is a powerful tool for in vivo tract tracing or functional imag- ing of the central nervous system. However Mn 21 may be toxic at high levels. In this study, we addressed the impact of Mn 21 on mouse hippo- campal neurons (HN) and neuron-like N2a cells in culture, using several approaches. Both HN and N2a cells not exposed to exogenous MnCl2 were shown by synchrotron X-ray fluorescence to contain 5 mg/g Mn. Concentrations of Mn 21 leading to 50% lethality (LC50) after 24 h of incubation were much higher for N2a cells (863 mM) than for HN (90 mM). The distribution of Mn 21 in both cell types exposed to Mn 21 concentrations below LC50 was perinuclear whereas that in cells exposed to concentrations above LC50 was more diffuse, suggesting an overloading of cell storage/detoxification capacity. In addition, Mn 21 had a cell-type and dose-dependent impact on the total amount of intra- cellular P, Ca, Fe and Zn measured by synchrotron X-ray fluorescence. For HN neurons, immunofluorescence studies revealed that concentra- tions of Mn 21 below LC50 shortened neuritic length and decreased mitochondria velocity after 24 h of incubation. Similar concentrations of Mn 21 also facilitated the opening of the mitochondrial permeability transition pore in isolated mitochondria from rat brains. The sensitivity of primary HN to Mn 21 demonstrated here supports their use as a rele- vant model to study Mn 21 -induced neurotoxicity. V C 2014 Wiley
Databáze: OpenAIRE
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