title: Methyl donor supplementation alters cognitive performance and motivation in female offspring from high-fat diet-fed dams.
abstract: During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)-fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior. Given that extensive brain development occurs during early postnatal life-particularly within the prefrontal cortex (PFC), a brain region critical for executive function-we examined whether early life methyl donor supplementation (e.g.,during adolescence) could ameliorate executive function deficits observed in offspring that were exposed to maternal HFD. By using operant testing, progressive ratio, and the PFC-dependent 5-choice serial reaction timed task (5-CSRTT), we determined that F1 female offspring (B6D2F1/J) from HFD-fed dams have decreased motivation (decreased progressive ratio breakpoint) and require a longer stimulus length to complete the 5-CSRTT task successfully, whereas early life methyl donor supplementation increased motivation and shortened the minimum stimulus length required for a correct response in the 5-CSRTT. Of interest, we found that expression of 2 chemokines, CCL2 and CXCL10, correlated with the median stimulus length in the 5-CSRTT. Furthermore, we found that acute adult supplementation of methyl donors increased motivation in HFD-fed offspring and those who previously received supplementation with methyl donors. These data point to early life as a sensitive time during which dietary methyl donor supplementation can alter PFC-dependent cognitive behaviors.-McKee, S. E., Grissom, N. M., Herdt, C. T., Reyes, T. M. Methyl donor supplementation alters cognitive performance and motivation in female offspring from high-fat diet-fed dams.
authors.affiliation: Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: McKee
authors.affiliation: Department of Psychology, College of Liberal Arts, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Grissom
authors.affiliation: Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Herdt
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA reyesta@ucmail.uc.edu.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Reyes
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects*; D059305:Diet, High-Fat / Q000009:adverse effects*; D019587:Dietary Supplements; D004334:Drug Administration Schedule; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D009042:Motivation / Q000187:drug effects*; D011247:Pregnancy
keywords: choline; folate; one carbon metabolism; operant; vitamin B12