Impact of manganese on primary hippocampal neurons from rodents. Issue 5 (3rd March 2014)

• Record Type: Journal Article
• Authors: Daoust, Alexia; Saoudi, Yasmina; Brocard, Jacques; Collomb, Nora; Batandier, Cécile; Bisbal, Mariano; Salomé, Murielle; Andrieux, Annie; Bohic, Sylvain; Barbier, Emmanuel L.
• Is Part Of: Hippocampus. Volume 24:Issue 5(2014:May)
• Page Start: 598
• Page End: 610
• Publication Date: 2014-03-03
• Subjects: Hippocampus (Brain) -- Periodicals; 612.825
• DOI: 10.1002/hipo.22252
• Languages: English
• ISSNs: 1050-9631

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>Manganese‐enhanced magnetic resonance imaging (MEMRI) is a powerful tool for in vivo tract tracing or functional imaging of the central nervous system. However Mn<sup>2+</sup> may be toxic at high levels. In this study, we addressed the impact of Mn<sup>2+</sup> on mouse hippocampal neurons (HN) and neuron‐like N2a cells in culture, using several approaches. Both HN and N2a cells not exposed to exogenous MnCl<sub>2</sub> were shown by synchrotron X‐ray fluorescence to contain 5 mg/g Mn. Concentrations of Mn<sup>2+</sup> 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<sup>2+</sup> in both cell types exposed to Mn<sup>2+</sup> 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<sup>2+</sup> had a cell‐type and dose‐dependent impact on the total amount of intracellular P, Ca, Fe and Zn measured by synchrotron X‐ray fluorescence. For HN neurons, immunofluorescence studies revealed that concentrations of Mn<sup>2+</sup> below LC50 shortened neuritic length and decreased mitochondria velocity after 24 h of incubation. Similar concentrations of Mn<sup>2+</sup> also facilitated the opening of the mitochondrial permeability transition pore in isolated mitochondria from rat brains. The sensitivity of primary HN to Mn<sup>2+</sup> demonstrated here supports their use as a relevant model to study Mn<sup>2+</sup>‐induced neurotoxicity. © 2014 Wiley Periodicals, Inc.</p> </abstract>