Over the past several years there has been an increased awareness as to the potential neurological hazards of environmental pollutants and other toxic agents. Our present knowledge concerning the sites of action in the CNS of these toxins is somewhat limited and is largely based on histological studies. Clearly, there is a need to develop new and better methods to quantitate the specific cellular and biochemical sites that are affected in brain upon exposure to these agents. Accordingly, the objective of this grant is the development of rapid and simple biochemical techniques to assess the sites of lesions produced in brain by neurotoxins. For this study two representative classes of neurotoxins, each producing a unique type of lesion in the CNS, will be examined. The two classes are represented by the neurotoxins, methylmercury and hexachlorophene. The specific studies that will be performed are: 1. Marker enzymes which are selectively localized in either neuronal, astroglial and oligodendroglial cells or in myelin will be used to quantitatively measure changes occurring in selected areas of rat brain exposed acutely and subacutely to varying concentrations of the specific neurotoxins, hexachlorophene and methylmercury. 2. To verify the lesions and to determine the sensitivity of the changes indicated by the biochemical marker enzymes, histopathological studies will be performed in a similar group of animals exposed to hexachlorophene and methylmercury. 3. Since a major portion of the development of the neurological pathways in rat brain occurs after birth, changes in the pattern of development of the different cell types will be monitored, as described in 1 and 2 above, after exposure to hexachlorophene and methylmercury. The methods for implementing the proposed neurochemical studies are all well established. They have been employed on a limited basis in the past and because of their general application and utility, it is appropriate to apply these methods to other neurotoxic agents as well. The marker enzymes chosen will allow us for the first time to determine the selective neurotoxicity of these agents as to degeneration of specific neurotransmitter classes of neurons (catacholinergic, cholinergic or GABAergic).
| Kung, M P; Kostyniak, P J; Olson, J R et al. (1989) Cell specific enzyme markers as indicators of neurotoxicity: effects of acute exposure to methylmercury. Neurotoxicology 10:41-52 |
| Kung, M P; Nickerson, P A; Sansone, F M et al. (1989) Effect of chronic exposure to hexachlorophene on rat brain cell specific marker enzymes. Neurotoxicology 10:201-10 |
| Kung, M P; Nickerson, P A; Sansone, F M et al. (1988) Effect of short-term exposure to hexachlorophene on rat brain cell specific marker enzymes. Fundam Appl Toxicol 11:519-27 |
| Francis, A; Whittemore, R; Jeffery, D R et al. (1987) Catecholamine-metabolizing enzyme activity in the nigrostriatal system. Biochem Pharmacol 36:2229-31 |
| Kung, M P; Roth, J A (1987) Cellular localization of soluble and membrane-bound forms of arylsulfatase in rat brain. Brain Res 419:141-6 |
| Kung, M P; Kostyniak, P; Olson, J et al. (1987) Studies of the in vitro effect of methylmercury chloride on rat brain neurotransmitter enzymes. J Appl Toxicol 7:119-21 |
