Screening pesticides for neuropathogenicity.

Pesticides are routinely screened in studies that follow specific guidelines for possible neuropathogenicity in laboratory animals. These tests will detect chemicals that are by themselves strong inducers of neuropathogenesis if the tested strain is susceptible relative to the time of administration and methodology of assessment. Organophosphate induced delayed neuropathy (OPIDN) is the only known human neurodegenerative disease associated with pesticides and the existing study guidelines with hens are a standard for predicting the potential for organophosphates to cause OPIDN. Although recent data have led to the suggestion that pesticides may be risk factors for Parkinsonism syndrome, there are no specific protocols to evaluate this syndrome in the existing study guidelines. Ideally additional animal models for human neurodegenerative diseases need to be developed and incorporated into the guidelines to further assure the public that limited exposure to pesticides is not a risk factor for neurodegenerative diseases.

Preferential effect of lead exposure during lactation on non-essential fatty acids in maternal organs.

This study determined the effects of lead exposure during the lactational period on maternal organ FA compositions in rat dams that were fed either an n-3 adequate (n-3 Adq) or deficient (n-3 Def) diet prior to conception. On giving birth, dams were subdivided into four groups in a 2 x 2 design with n-3 FA supply and Pb exposure as the dependent variables. Pb acetate (0.2 wt%) was administered in the drinking water from the time they gave birth to weaning 3 wk later. Following weaning, the dams were decapitated, and the liver, plasma, kidney, brain, and retina analyzed for FA composition. The n-3 deficient diets markedly decreased the percentages of total n-3 FA, including docosahexaenoic acid (DHA), and increased total n-6 FA including both arachidonic (AA) and n-6 docosapentaenoic acids in all tissues (P < 0.05). The principal effects of Pb occurred in the liver and plasma, where 20-32% losses in total FA concentration concurrent with increased relative percentages of AA (P < 0.05) were observed. In kidney, the percentages of AA and DHA also increased after Pb exposure (P < 0.05) with lesser effects in the nervous system. There was a diet x Pb interaction for liver, plasma, and retinal 20-C n-6 PUFA (P < 0.05). Generally, shorter-chain saturated and monounsaturated FA concentrations were decreased after Pb exposure. An analysis of the changes in the tissue concentrations induced by Pb indicated that the increases in the percentages of PUFA likely reflected a preferential loss of non-EFA. The mechanisms by which Pb affects saturated and monounsaturated FA concentration are unknown.

Lead exposure and (n-3) fatty acid deficiency during rat neonatal development affect subsequent spatial task performance and olfactory discrimination.

Docosahexaenoic acid [22:6(n-3), DHA] is important for optimal infant central nervous system development, and lead (Pb) exposure during development can produce neurological deficits. Long-Evans strain rats were fed either an (n-3) deficient [(n-3) Def] diet to produce brain DHA deficiency, or an adequate [(n-3) Adq] diet through 2 generations. At the birth of the 2nd generation, the dams were subdivided into 4 groups and supplied drinking water containing either 5.27 mmol/L (Pb) or sodium (Na) acetate until weaning. Rats were killed at 3 wk (weaning) and 11 wk (maturity) for brain Pb and fatty acid analysis. Spatial task and olfactory-cued behavioral assessments were initiated at 9 wk. Rats in the (n-3) Def group had a 79% lower concentration of brain DHA compared with the (n-3) Adq group with no effect of Pb exposure. At weaning, Pb concentrations were 7.17 +/- 0.47 nmol Pb/g of brain (wet weight) in the (n-3) Adq-Pb group and 6.49 +/- 0.63 nmol Pb/g of brain (wet weight) in the (n-3) Def-Pb group. At maturity, the brains contained 1.30 +/- 0.22 and 1.07 +/- 0.12 nmol Pb/g (wet weight), respectively. In behavioral testing, significant effects of both Pb and DHA deficiency were observed in the Morris water maze probe trial and in 2-odor olfactory discrimination acquisition and olfactory-based reversal learning tasks. Both lactational Pb exposure and (n-3) fatty acid deficiency led to behavioral deficits with additive effects observed only in the acquisition of 2-odor discriminations.

Lead exposure and (n-3) fatty acid deficiency during rat neonatal development alter liver, plasma, and brain polyunsaturated fatty acid composition.

Lead (Pb) exposure has been reported to increase arachidonic (AA) and docosahexaenoic (DHA) acids. To determine whether Pb effects on fatty acid composition are influenced by dietary (n-3) fatty acid restriction, weanling female rats were fed either an (n-3)-adequate or -deficient diet to maturity and mated. At parturition, dams in each group were subdivided to receive either 0.2% Pb or Na-acetate in their drinking water during lactation only. Pups were analyzed for fatty acid content in liver, plasma, and brain at either 3 or 11 wk. The (n-3)-deficient diets markedly decreased total (n-3) fatty acids, and increased total (n-6) fatty acids including both AA and docosapentaenoic (n-6) in each compartment (P < 0.05). The main effects of Pb were in the livers of weanling rats where there was a 56% loss in total fatty acid concentration concurrent with increased relative percentages of AA and DHA. Thus, because there was a greater percentage of liver nonessential fatty acid lost relative to the essential fatty acids (EFA), there was no net change in AA concentration. There was a diet x Pb interaction for a decrease in liver DHA concentration evident only in the (n-3)-adequate group. There were also diet x Pb interactions in plasma at 11 wk and in brain at 3 wk. These data are consistent with the hypothesis of a Pb-induced increase in fatty acid catabolism, perhaps as a source of energy.