Assessing the role of astrocytes in manganese developmental neurotoxicity

Manganese (Mn) is both an essential nutrient and a neurotoxic element. High Mn content in drinking water has been associated with lower intelligence quotient and Attention-Deficit Hyperactivity Disorders. Although there is growing concern about the developmental neurotoxicity of Mn, it has only recently begun to be explored. We hypothesize that astrocytes can protect neurons from Mn toxicity by protecting synapses, whereas when astrocytic protection is overwhelmed, Mn can reach synapses, presumably through competition with Ca signaling pathways. X-ray fluorescence microscopy will enable to map and quantify Mn distribution in co-cultures of neurons and astrocytes. Primary rat hippocampal neurons will be cultured alone, or with astrocytes and exposed to non-toxic or toxic Mn concentrations. We expect a reduced Mn content in neurons cultured with astrocytes. We will elucidate if Mn reaches the synaptic compartments when the astrocytic protection is overpassed at high Mn exposure levels.