title: Prenatal stress-induced increases in hippocampal von Willebrand factor expression are prevented by concurrent prenatal escitalopram.
abstract: Prenatal stress has been linked to deficits in neurological function including deficient social behavior, alterations in learning and memory, impaired stress regulation, and susceptibility to adult disease. In addition, prenatal environment is known to alter cardiovascular health; however, limited information is available regarding the cerebrovascular consequences of prenatal stress exposure. Vascular disturbances late in life may lead to cerebral hypoperfusion which is linked to a variety of neurodegenerative and psychiatric diseases. The known impact of cerebrovascular compromise on neuronal function and behavior highlights the importance of characterizing the impact of stress on not just neurons and glia, but also cerebrovasculature. Von Willebrand factor has previously been shown to be impacted by prenatal stress and is predictive of cerebrovascular health. Here we assess the impact of prenatal stress on von Willebrand factor and related angiogenic factors. Furthermore, we assess the potential protective effects of concurrent anti-depressant treatment during in utero stress exposure on the assessed cerebrovascular endpoints. Prenatal stress augmented expression of von Willebrand factor which was prevented by concurrent in utero escitalopram treatment. The functional implications of this increase in von Willebrand factor remain elusive, but the presented data demonstrate that although prenatal stress did not independently impact total vascularization, exposure to chronic stress in adulthood decreased blood vessel length. In addition, the current study demonstrates that production of reactive oxygen species in the hippocampus is decreased by prenatal exposure to escitalopram. Collectively, these findings demonstrate that the prenatal experience can cause complex changes in adult cerebral vascular structure and function.
authors.affiliation: Department of Psychiatry and Behavioral Sci., Emory University, Atlanta, GA, USA; Department of Physiology, Emory University, Atlanta, GA, USA. Electronic address: gretchen.mccandless@vcuhealth.org.
authors.forename: Gretchen N
authors.initials: GN
authors.lastname: Neigh
authors.affiliation: Department of Physiology, Emory University, Atlanta, GA, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Nemeth
authors.affiliation: Department of Psychiatry and Behavioral Sci., Emory University, Atlanta, GA, USA.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Kelly
authors.affiliation: Department of Psychiatry and Behavioral Sci., Emory University, Atlanta, GA, USA.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Hardy
authors.affiliation: Department of Psychiatry and Behavioral Sci., Emory University, Atlanta, GA, USA.
authors.forename: Chase
authors.initials: C
authors.lastname: Bourke
authors.affiliation: Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Zachary N
authors.initials: ZN
authors.lastname: Stowe
authors.affiliation: Department of Psychiatry and Behavioral Sci., Emory University, Atlanta, GA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owens
mesh_terms: D000367:Age Factors; D000679:Amygdala / Q000098:blood supply; D042501:Angiogenic Proteins / Q000096:biosynthesis; D000818:Animals; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017397:Prefrontal Cortex / Q000098:blood supply; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000517:prevention & control*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D014841:von Willebrand Factor / Q000096:biosynthesis*
chemical_list: D042501:Angiogenic Proteins; D017382:Reactive Oxygen Species; D014841:von Willebrand Factor; D015283:Citalopram
keywords: Escitalopram; Prenatal stress; Reactive oxygen species; Stress; Vascular length; Von Willebrand factor