Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress Áine T. Behan a , ⁎ , 1 , Daniel L.A. van den Hove b , 1 , Lynn Mueller b , Marlon J.A. Jetten b , Harry W.M. Steinbusch b , David R. Cotter a , ⁎ , 2 , Jos Prickaerts b , 2 a Department of Psychiatry, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland b Department of Neuroscience, School for Mental Health and Neuroscience (MHeNS), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands Received 23 December 2009; received in revised form 2 June 2010; accepted 19 July 2010 KEYWORDS Prenatal stress; Mice; Hippocampus; Sexual dimorphism; Psychiatric disorders Abstract Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychi- atric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS. © 2010 Elsevier B.V. and ECNP. All rights reserved. 1. Introduction The human brain is highly vulnerable to stressors during foetal development. Recent human studies have demonstrated that exposure of a pregnant woman to prenatal stress (PS) may impair biological and behavioural responses in their offspring in later life (Weinstock, 2008). This includes an increased vulnerability to neuropsychiatric disorders in later life such as anxiety (Beydoun and Saftlas, 2008), depression (Beydoun and Saftlas, 2008; Maccari et al., 2003), autism (Kinney et al., 2008) and schizophrenia (Koenig et al., 2002). PS in rodents is accompanied by an hyper-reactive hypothalamo–pituitary–adrenal (HPA) axis (Maccari et al., 1995; Morley-Fletcher et al., 2003) that is thought to cause an increase in anxiety (Vallee et al., 1997; Van den ⁎ Corresponding authors. Tel.: +353 1 402 8512, +353 1 809 3860; fax: +353 1 402 2447, +353 1 809 3741. E-mail addresses: abehan@rcsi.ie (Á.T. Behan), drcotter@rcsi.ie (D.R. Cotter). 1 Authors contributed equally to this work. 2 Both are senior/final authors in this work. 0924-977X/$ - see front matter © 2010 Elsevier B.V. and ECNP. All rights reserved. doi:10.1016/j.euroneuro.2010.07.004 www.elsevier.com/locate/euroneuro European Neuropsychopharmacology (2011) 21, 71–79