title: Decreased reelin expression and organophosphate pesticide exposure alters mouse behaviour and brain morphology.
abstract: Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders, including ASDs (autism spectrum disorders). In this study, we examined the combinatorial effect of two factors thought to be involved in autism--reduction in the expression of the extracellular matrix protein reelin and prenatal exposure to an organophosphate pesticide, CPO (chlorpyrifos oxon). Mice with reduced reelin expression or prenatal exposure to CPO exhibited subtle changes in ultrasound vocalization, open field behaviour, social interaction and repetitive behaviour. Paradoxically, mice exposed to both variables often exhibited a mitigation of abnormal behaviours, rather than increased behavioural abnormalities as expected. We identified specific differences in males and females in response to both of these variables. In addition to behavioural abnormalities, we identified anatomical alterations in the olfactory bulb, piriform cortex, hippocampus and cerebellum. As with our behavioural studies, anatomical alterations appeared to be ameliorated in the presence of both variables. While these observations support an interaction between loss of reelin expression and CPO exposure, our results suggest a complexity to this interaction beyond an additive effect of individual phenotypes.
authors.affiliation: Department of Psychiatry and Biobehavioral Science, UCLA School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Mullen
authors.forename: Elvira
authors.initials: E
authors.lastname: Khialeeva
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Hoffman
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Ghiani
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Carpenter
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001526:Behavioral Symptoms / Q000139:chemically induced*; D001921:Brain / Q000187:drug effects*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D003124:Colorimetry; D016503:Drug Delivery Systems; D004622:Embryo, Mammalian; D005106:Exploratory Behavior / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000235:genetics; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010755:Organophosphates / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D014828:Vocalization, Animal / Q000187:drug effects; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D010755:Organophosphates; D012333:RNA, Messenger; D000091042:Reelin Protein; D000110:Acetylcholinesterase; D001616:beta-Galactosidase; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases