title: Sex differences in effects of low level domoic acid exposure.
abstract: Consumption of seafood containing the phytoplankton-derived toxin domoic acid (DOM) causes neurotoxicity in humans and in animals. It has been reported that DOM-induced symptoms may be more severe in men than women, but to date the effect of sex on DOM-induced effects in adults is not known. We investigated sex differences in DOM-induced effects in adult rats. Since low level exposure is of greatest relevance to human health (due to DOM regulatory limit), we examined the effects of low level exposure. Adult male and female Sprague Dawley rats were administered a single intraperitoneal injection of DOM (0, 1.0, 1.8 mg/kg). Behaviour was monitored for 3h and immunohistochemistry in the dorsal hippocampus and olfactory bulb was also examined. DOM increased locomotor and grooming activity, compared to vehicle group. DOM exposure also significantly increased stereotypic behaviours and decreased phosphorylated cAMP response element-binding protein immunoreactivity (pCREB-IR). There was no effect of sex on the magnitude of the behavioural responses, but the onset of DOM-induced locomotor activity and ear scratches was quicker in females than in males. Mixed effect modelling revealed the predicted peak in locomotor activity in response to DOM was also quicker in females than in males. Severe toxicity was evident in 2/7 male rats and 0/8 female rats dosed with 1.8 mg/kg DOM. These data suggest that males exposed to low level DOM may be more susceptible to severe neurotoxicity, whereas females are affected more quickly. Understanding sex differences in DOM-induced neurotoxicity may contribute to future protective strategies and treatments.
authors.affiliation: Medical Toxicology Centre, Newcastle University, Newcastle upon Tyne NE2 4AA, UK. andrew.baron@ncl.ac.uk
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Baron
authors.forename: Steven P
authors.initials: SP
authors.lastname: Rushton
authors.forename: Natalie
authors.initials: N
authors.lastname: Rens
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Morris
authors.forename: Peter G
authors.initials: PG
authors.lastname: Blain
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Judge
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006120:Grooming / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D008387:Marine Toxins / Q000008:administration & dosage / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D057096:Shellfish Poisoning / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
chemical_list: C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D005904:Glial Fibrillary Acidic Protein; D008387:Marine Toxins; C012301:domoic acid; D007608:Kainic Acid