Spatial and visual discrimination reversals in adult and geriatric rats exposed during gestation to methylmercury and n-3 polyunsaturated fatty acids.

Fish contain essential long chain polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), an omega-3 (or n-3) PUFA, but are also the main source of exposure to methylmercury (MeHg), a potent developmental neurotoxicant. Since n-3 PUFAs support neural development and function, benefits deriving from a diet rich in n-3s have been hypothesized to protect against deleterious effects of gestational MeHg exposure. To determine whether protection occurs at the behavioral level, female Long-Evans rats were exposed, in utero, to 0, 0.5, or 5ppm of Hg as MeHg via drinking water, approximating exposures of 0, 40, and 400 microgHg/kg/day and producing 0, 0.29, and 5.50ppm of total Hg in the brains of siblings at birth. They also received pre- and postnatal exposure to one of two diets, both based on the AIN-93 semipurified formulation. A "fish-oil" diet was high in, and a "coconut-oil" diet was devoid of, DHA. Diets were approximately equal in alpha-linolenic acid and n-6 PUFAs. As adults, the rats were first assessed with a spatial discrimination reversal (SDR) procedure and later with a visual (nonspatial) discrimination reversal (VDR) procedure. MeHg increased the number of errors to criterion for both SDR and VDR during the first reversal, but effects were smaller or non-existent on the original discrimination and on later reversals. No such MeHg-related deficits were seen when the rats were retested on SDR after 2 years of age. These results are consistent with previous reports and hypotheses that gestational MeHg exposure produces perseverative responding. No interactions between diet and MeHg were found, suggesting that n-3 PUFAs do not guard against these behavioral effects. Brain Hg concentrations did not differ between the diets, either. In geriatric rats, failures to respond were less common and response latencies were shorter for rats fed the fish-oil diet, suggesting that exposure to a diet rich in n-3s may lessen the impact of age-related declines in response initiation.

World-wide consumption of trans fatty acids.

Dietary trans fatty acids (TFA) originate from commercially hydrogenated oils and from dairy and meat fats. Estimates of dietary TFA consumption vary with dietary habits and food supply as well as methods used to estimate consumption. Methods include: (1) market share data, (2) laboratory analysis of duplicate portions or composite diets, (3) analysis of consumption data of a representative population, and (4) biomarkers, such as human milk. In North America, daily intakes have been estimated by food frequency questionnaire to be 3-4 g/person and by extrapolation of human milk data to be greater than 10 g/person. Diets in northern Europe traditionally have contained more TFA than in Mediterranean countries where olive oil is used. Intakes in Europe range from minimal values in Italy, Portugal, Greece and Spain (1.4-2.1 g/day) to greater values for Germany, Finland, Denmark, Sweden, France, United Kingdom, Belgium, Norway, The Netherlands, and Iceland (2.1-5.4 g/day) Recent decreases in dietary TFA have been observed due to modifications of commercial fats and changes in consumer choices. The impact of legislation restricting use of hydrogenated fats and requiring TFA content on food labels awaits future studies.

Gestational exposure to methylmercury and n-3 fatty acids: effects on high- and low-rate operant behavior in adulthood.

Fish in the diet is the major source of methylmercury (MeHg) exposure, but eating fish also provides important nutrients. Many fish species contain essential long chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), an omega-3 (or n-3) fatty acid, that is important for neural development and function. To examine interactions between MeHg and n-3 fatty acids, female Long-Evans rats were exposed, in utero, to 0, 0.5, or 5 ppm MeHg via drinking water, approximating exposures of 0, 40, and 400 mug/kg/day. They also received pre- and postnatal exposure to a diet containing either fish oil or coconut oil, creating a 2 (Diet)x3 (MeHg) full factorial design, with 6-8 rats per cell. The diets were high or marginal, respectively, in n-3 fatty acids but approximately equal in n-6 fatty acids. No exposure-related effects on developmental milestones or growth were noted. Behavior was evaluated using a series of rapidly increasing fixed ratio (FR) schedules of sucrose reinforcement; 1, 5, 25 and 75 lever presses were required for sucrose delivery, with three sessions provided at each requirement. This phase was followed by four sessions of a differential-reinforcement-of-low-rate-behavior (DRL) schedule, in which presses preceded by 10 s (or more) without a press were reinforced. Subsequently, several progressive ratio (PR) schedules that increased response requirements throughout a single session by a rate of 5%, 10%, or 20% were imposed. Rats exposed during gestation to MeHg had significantly higher response rates than controls under the large FR schedules, during the first session of DRL, and the PR 5% schedule, but neither fish oil nor coconut oil modified MeHg's effects. This finding is consistent with hypotheses that developmental MeHg exposure produced perseverative responding or altered the sensitivity of behavior to its reinforcing consequences and that certain reinforcement contingencies can unmask MeHg's effects.

Urolithiasis in rats consuming a dl bitartrate form of choline in a purified diet.

Urolithiasis appeared in rats maintained to study the effects of nutrients and methylmercury on development and aging. After a year, the mortality rate was approximately 10%, and by 2 years, it had increased to nearly 30%. Clinical signs and urinary tract pathology were examined as a function of diet, duration on diet, gender, methylmercury exposure, genetics, and other potential risk factors by using survival analyses and qualitative comparisons. Urolithiasis in female rats appeared 15 weeks after beginning a purified diet and after 5 weeks for male rats. After 97 weeks, the mortality rate of female rats was 22% and for male rats was 64%. Lifetime urolithiasis-associated mortality was about 2% in a group of rats that consumed the contaminated diet for < 30 weeks. No urolithiasis occurred in siblings or cohorts of the rats described here that were maintained on a standard rodent chow containing choline chloride. Urolithiasis was traced to racemic, rather than levo-, bitartaric acid in some purified diets shipped in 2001 and 2002. It is unknown when the impurity first appeared in the diet, so estimates of exposure duration are upper limits. Chronic methylmercury exposure increased vulnerability. Some families (dam + offspring) had multiple cases of urolithiasis, but probability models constructed to evaluate familial clustering revealed no evidence for a genetic predisposition to urolithiasis apart from gender. Removing racemic tartaric acid did not decrease mortality once rats had been on the diet for 20 to 30 weeks, but it helped when exposure duration was shorter.