title: Dietary choline supplementation to dams during pregnancy and lactation mitigates the effects of in utero stress exposure on adult anxiety-related behaviors.
abstract: Brain cholinergic dysfunction is associated with neuropsychiatric illnesses such as depression, anxiety, and schizophrenia. Maternal stress exposure is associated with these same illnesses in adult offspring, yet the relationship between prenatal stress and brain cholinergic function is largely unexplored. Thus, using a rodent model, the current study implemented an intervention aimed at buffering the potential effects of prenatal stress on the developing brain cholinergic system. Specifically, control and stressed dams were fed choline-supplemented or control chow during pregnancy and lactation, and the anxiety-related behaviors of adult offspring were assessed in the open field, elevated zero maze and social interaction tests. In the open field test, choline supplementation significantly increased center investigation in both stressed and nonstressed female offspring, suggesting that choline-supplementation decreases female anxiety-related behavior irrespective of prenatal stress exposure. In the elevated zero maze, prenatal stress increased anxiety-related behaviors of female offspring fed a control diet (normal choline levels). However, prenatal stress failed to increase anxiety-related behaviors in female offspring receiving supplemental choline during gestation and lactation, suggesting that dietary choline supplementation ameliorated the effects of prenatal stress on anxiety-related behaviors. For male rats, neither prenatal stress nor diet impacted anxiety-related behaviors in the open field or elevated zero maze. In contrast, perinatal choline supplementation mitigated prenatal stress-induced social behavioral deficits in males, whereas neither prenatal stress nor choline supplementation influenced female social behaviors. Taken together, these data suggest that perinatal choline supplementation ameliorates the sex-specific effects of prenatal stress.
authors.affiliation: Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Building 500, 1300 East 17th Place, Aurora, CO 80045, USA. Electronic address: Kalynn.Schulz@UCDenver.edu.
authors.forename: Kalynn M
authors.initials: KM
authors.lastname: Schulz
authors.affiliation: Neuroscience Program, University of Colorado Anschutz Medical Campus, RC-1, MS 8351, Rm 7107 12800 E. 19th Ave, Aurora, CO 80045, USA.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Pearson
authors.affiliation: Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Building 500, 1300 East 17th Place, Aurora, CO 80045, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Gasparrini
authors.affiliation: Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Building 500, 1300 East 17th Place, Aurora, CO 80045, USA.
authors.forename: Kayla F
authors.initials: KF
authors.lastname: Brooks
authors.affiliation: Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Building 500, 1300 East 17th Place, Aurora, CO 80045, USA.
authors.forename: Chakeer
authors.initials: C
authors.lastname: Drake-Frazier
authors.affiliation: Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Building 500, 1300 East 17th Place, Aurora, CO 80045, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Zajkowski
authors.affiliation: Neuroscience Department, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260, USA.
authors.forename: Alison D
authors.initials: AD
authors.lastname: Kreisler
authors.affiliation: Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Building 500, 1300 East 17th Place, Aurora, CO 80045, USA.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Adams
authors.affiliation: Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Building 500, 1300 East 17th Place, Aurora, CO 80045, USA; Neuroscience Program, University of Colorado Anschutz Medical Campus, RC-1, MS 8351, Rm 7107 12800 E. 19th Ave, Aurora, CO 80045, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Leonard
authors.affiliation: Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Building 500, 1300 East 17th Place, Aurora, CO 80045, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Stevens
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000503:physiopathology / Q000517:prevention & control*; D001835:Body Weight; D002794:Choline / Q000008:administration & dosage*; D019587:Dietary Supplements; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009483:Neuropsychological Tests; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D012919:Social Behavior; D013315:Stress, Psychological / Q000175:diagnosis* / Q000503:physiopathology
chemical_list: D002794:Choline
keywords: Anxiety; Choline; Diet; Hippocampus; Maternal stress; Nicotinic acetylcholine receptor; Prenatal stress; Psychopathology; Supplementation