Neurotoxic effects of mercury on auditory cortex networks growing on microelectrode arrays: a preliminary analysis.
Mercury is known to cause sensorineural hearing loss and impaired speech perception. However, there is still a lack of a quantitative description of mercury toxicity on central auditory structures. This is a preliminary study using the novel technique of microelectrode array (MEA) recordings to evaluate acute and chronic neurotoxic effects of mercury on auditory cortex networks (ACNs) in vitro. Morphological and electrophysiological effects of mercuric chloride (HgCl(2)) were studied. Neurons dissociated from auditory cortices of 14-day-old mouse embryos were grown on photoetched MEAs containing 64 transparent indium-tin oxide (ITO) electrodes. For acute electrophysiological experiments, the spontaneous spiking and bursting activity from ACNs were compared before and after application of HgCl(2). For chronic electrophysiological experiments, auditory cortex cultures were treated with various concentrations of HgCl(2) from the day of seeding, and were tested 4 weeks later for the presence of spontaneous activity. Morphological analysis was conducted on 8-day-old ACNs treated with HgCl(2) for 3 days. Results of acute experiments indicated that <75 mM of HgCl(2) had an excitatory effect of variable magnitude on the spontaneous activity of ACNs; however, concentrations above 100 microM completely and irreversibly inhibited spike and burst activity. Chronic exposure of ACNs to 10 microM HgCl(2) completely blocked the spontaneous activity. Morphological analysis indicated that 10 microM HgCl(2) caused neuronal cell death in 3 days. It is concluded that HgCl(2) has a more toxic effect on auditory networks when exposed chronically, and the levels of mercury showing toxic effects on ACNs are within the dose range shown to cause neurologic symptoms in humans.
Gopal
Kamakshi V
KV
Department of Speech and Hearing Sciences and Center for Network Neuroscience, University of North Texas, PO Box 305010, Denton, TX 76203, USA. gopal@unt.edu
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001303:Auditory Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D006313:Hearing Loss, Central / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008627:Mercuric Chloride / Q000633:toxicity; D008628:Mercury / Q000633:toxicity*; D020262:Mercury Poisoning, Nervous System / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008839:Microelectrodes / Q000592:standards; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009415:Nerve Net / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy
D008627:Mercuric Chloride; D008628:Mercury