domoic-acid and Body-Weight

Changes in glutamatergic signalling during neonatal development are known to result in long-lasting changes in brain function. Previous work in our laboratory has shown that systemic administration of very low (subconvulsive) doses of the kainate receptor agonist, domoic acid, during the second postnatal week in the rat results in behavioural and histopathological changes that manifest in adulthood. Notably, however, the behavioural response, that resembles a low grade seizure, appears to not be spontaneous but occurs in response to exposure to novel environments. Our aim in the current study was to use both behavioural analysis and measures of serum corticosterone and ACTH to determine if this response represents an exaggerated physiological response to mild stress. Groups of male and female SD rats were injected (s.c.) with low dose domoate between postnatal days 8-14. No significant changes in serum corticosterone concentrations were detectable on day 14. At 75 days of age, separate cohorts of rats that had received perinatal domoate treatment were sampled and assayed for serum corticosterone and ACTH before, during and after exposure to a novel water maze. Data revealed a significant incidence of behavioural seizures in treated rats with no false positives. Both saline and domoate-treated rats also showed a consistent physiological stress response that was not different between groups. Immunocytochemistry for glucocorticoid and mineralocorticoid receptors in hippocampal and hypothalamic subfields also revealed no consistent difference between groups. We conclude that neonatal domoate results in behavioural seizures in adult rats that probably originate from something other than an enhanced physiological response to mild stress.

Topics: Adrenocorticotropic Hormone; Animals; Animals, Newborn; Behavior, Animal; Body Weight; Corticosterone; Environment; Female; Immunohistochemistry; Kainic Acid; Male; Maze Learning; Neuromuscular Depolarizing Agents; Pregnancy; Rats; Rats, Sprague-Dawley; Receptors, Glucocorticoid; Receptors, Mineralocorticoid; Seizures; Stress, Psychological; Swimming

The depuration kinetics of the domoic acid of four body fractions (digestive gland, adductor muscle, gonad+kidney and gills+mantle) of the scallop Pecten maximus was studied over 295 days. The scallops, which had acquired the toxins during a Pseudo-nitzschia australis episode that took place the week before the beginning of the experiment, were maintained in tanks with running seawater. All the body fractions, except the adductor muscle, decreased their domoic acid burden throughout the experiment. The amount of toxin in the muscle dropped sharply at the start of the experiment but increased again at the end, to levels that were higher than the initial ones. Several dynamic models of depuration kinetics, which included the depuration of each fraction (excluding the adductor muscle) and the transfers between them, were constructed, implemented and fitted to the data to obtain their parameters. The estimated depuration rates were very low, both considering and not considering the transfer of toxin between organs or the effect of weight loss. There were strong differences in the domoic acid burden of the body fractions studied but not between their depuration rates. No net transfer from the digestive gland, the tissue with highest domoic acid concentration, to the other fractions was found, as the inclusion of these processes in the models produced only a marginally better fit to the data. The depuration of domoic acid was slightly, but significantly, affected by biomass. Weight loss induced domoic acid loss, suggesting that part of the depuration may be produced by the direct loss of bivalve cells. The concentration or dilution effect, due to decreases or increases in biomass, documented for other species and toxins, has little importance in Pecten maximus.

Topics: Animals; Biomass; Body Weight; Environmental Exposure; Kainic Acid; Kinetics; Mollusca; Neuromuscular Depolarizing Agents; Tissue Distribution

The lateral septal area (LSA) has been implicated in the control of various psychoneuroendocrine processes in the rat. Interactions between the endocrine and immune systems and sex differences in immunity reflect the interdependence of the immune and neuroendocrine systems. Kainic acid (KA) lesions in the lateral septal area not only modify neuroendocrine processes, but also produce a suppression of humoral immunity in female rats. Presently, we have evaluated the effects of neurotoxic lesions in the LSA on the humoral immune response and body weight regulation of male and female rats. Bilateral lesions in the LSA of adult male and female rats were produced by stereotaxically infusing either 0.25 microliters of kainic acid (1.5 micrograms/microliters) or 0.5 microliters of domoic acid (DA; 0.3 micrograms/microliters) into the LSA. In an additional study, LSA lesions using 0.25 microliters of DA (0.6 micrograms/microliters) were produced in female rats only. Sham operations consisted of bilateral injections of 0.9% saline into the LSA. The effects of these lesions on antibody production, following immunization with 100 micrograms ovalbumin in complete Freund's adjuvant, were examined. Blood samples were collected on Days 7 and 14 following immunization. The anti-ovalbumin IgM and IgG antibody titers were measured by an enzyme amplified ELISA assay. As found previously, KA-induced LSA lesions in adult female rats produced an increase in body weight and a suppression of the humoral immune response. However, LSA lesions produced with the neurotoxin DA had a similar effect on body weight but had no effect on humoral immunity. In male rats, neither body weight regulation nor the humoral immune response was affected by KA or DA lesions in the LSA. These results indicate that the effects of neurotoxic LSA lesions on body weight regulation and the humoral immune response are sex specific and further demonstrate that two closely related kainate neurotoxins have differential effects on the humoral immune response, but have similar effects on body weight regulation. Thus, neurons in the LSA of female rats that are involved in the inhibitory control of body weight are susceptible to both KA and DA, whereas neurons in the LSA associated with immunoregulation are differentially affected by KA and DA. Of further interest, a sex difference in DA susceptibility was noted, with male rats showing greater cell loss in the LSA following DA infusions, as compared to female rats

Topics: Animals; Antibodies; Antibody Formation; Body Weight; Female; Immune System; Immunoglobulin G; Immunoglobulin M; Kainic Acid; Male; Organ Size; Rats; Rats, Inbred Strains; Septum Pellucidum; Sex Characteristics; Sexual Behavior, Animal