title: Impact of manganese on primary hippocampal neurons from rodents.
abstract: 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(2+) may be toxic at high levels. In this study, we addressed the impact of Mn(2+) on mouse hippocampal 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(2+) 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(2+) in both cell types exposed to Mn(2+) 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(2+) 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(2+) below LC50 shortened neuritic length and decreased mitochondria velocity after 24 h of incubation. Similar concentrations of Mn(2+) also facilitated the opening of the mitochondrial permeability transition pore in isolated mitochondria from rat brains. The sensitivity of primary HN to Mn(2+) demonstrated here supports their use as a relevant model to study Mn(2+) -induced neurotoxicity.
authors: Inserm, U836, Grenoble, France; Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.
authors: Alexia
authors: A
authors: Daoust
authors: Yasmina
authors: Y
authors: Saoudi
authors: Jacques
authors: J
authors: Brocard
authors: Nora
authors: N
authors: Collomb
authors: Cécile
authors: C
authors: Batandier
authors: Mariano
authors: M
authors: Bisbal
authors: Murielle
authors: M
authors: Salomé
authors: Annie
authors: A
authors: Andrieux
authors: Sylvain
authors: S
authors: Bohic
authors: Emmanuel L
authors: EL
authors: Barbier
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology*; D008345:Manganese / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D010758:Phosphorus / Q000378:metabolism; D013052:Spectrometry, X-Ray Emission; D013997:Time Factors; D014131:Trace Elements / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism
chemical_list: D014131:Trace Elements; D010758:Phosphorus; D008345:Manganese; D015032:Zinc; D002118:Calcium
keywords: MEMRI; X-ray synchrotron; hippocampal neurons; manganese; mitochondria