As an advantage of the planned collaboration between the 5 laboratories in the frame of the present project, the different methods applied would increase the effectiveness of the diagnosis of subclinical damage to the nervous system in chronic mercury intoxication.
The following questions will be investigated :
the development of sensitive methods to detect neurotoxic effects in neocortical cells,
the study of the sequential expression of toxic effects : (cyto-) genetic endpoints versus cell death (apoptosis) versus neurophysiological changes,
the analysis of chronic low level and transplacental exposure to environmentally relevant pollutants on electrophysiological functions of mammalian neocortex at cellular and network level in adult and developing nervous system,
the analysis of the effects of MMC intoxication on the initiation, maintenance and propagation of epileptiform activity of the neocortex,
the role of different kinds of excitatory aminoacid receptors (NMDA and non-NMDA, AMPA receptors) on the initiation, maintenance and propagation of epileptiform activity of the neocortex in MMC intoxicated animals,
effect of MMC exposure on metabolism, convulsant activity and neurotoxicity of kynurenic acid.
The alkylmercury compounds, especially methylmercury (MMC), are the most dangerous and common sources of mercury toxicity, because of both their widespread use as fungicides and the fact that methylmercury is made by bacteria from elemental mercury. The principal sites of mercury deposition is the central nervous system, after exposure to alkyl mercury compounds which are highly accumulative. The general health condition of the population is influenced by mercury intoxication, which is indicated by an increased probability of epilepsy. However, the exact neuro-physiological bases of links between epilepsy and mercury intoxication are not analyzed yet.
To understand the clinical picture of a toxic effect, knowledge of the basic mechanisms on the cellular level is essential. The understanding of the mechanisms by which mercury ions exert their neurotoxic effects would not only increase our basic knowledge in nervous system function, but may allow better ways to treat and prevent human disease due to exposure to these chemicals. It is aimed to compare the cytotoxic and genotoxic effects of MMC in neocortical neurons of newborn rats of mothers, who were treated chronically by MMC before and during pregnancy together with changes of their multimodal electrophysiological parameters. This comparison will allow to assess whether the neurophysiological changes are primary events or consequences of early genetic events, moreover the balance between cell survival versus cell death will be analyzed in function of neurophysiological performance. Investigation of basic electrophysiological membrane-, and synaptic parameters at cellular level, as well as the analyses of the probability of occurrence, and the manifestation of different forms of epilepsy in experimental models, could give an important contribution to understand the possible changes in the function of the neocortical neuronal networks.
Funding SchemeCSC - Cost-sharing contracts
20 950 Lublin
SA2 8PP Swansea