Intranasal exposure to manganese disrupts neurotransmitter release from glutamatergic synapses in the central nervous system in vivo

摘要: Abstract Chronic exposure to aerosolized manganese induces a neurological disorder that includes extrapyramidal motor symptoms and cognitive impairment. Inhaled can bypass the blood–brain barrier reach central nervous system by transport down olfactory nerve brain's bulb. However, mechanism which Mn disrupts neural function remains unclear. Here we used optical imaging techniques visualize exocytosis in terminals vivo mouse Acute via intranasal instillation of 2–200 μg MnCl2 solution caused dose-dependent reduction odorant-evoked neurotransmitter release, with significant effects at as little 2 μg 90% compared vehicle controls 200 μg exposure. This was also observed response direct electrical stimulation layer bulb, demonstrating Mn's action is occurring centrally, not peripherally. first evidence intoxication disrupt consistent previous work suggesting chronic limits amphetamine-induced dopamine increases basal ganglia despite normal levels synthesis (Guilarte et al., J Neurochem 2008). The commonality between glutamatergic neurons bulb dopaminergic suggests disruption release may be general consequence wherever accumulates brain could underlie its pleiotropic effects.