Adrenalectomy and corticosterone replacement differentially alter CA3 dendritic morphology and new cell survival in the adult rat hippocampus M. Martı´nez-Claros a , H.W.M. Steinbusch a , A. van Selm a , D.L.A. van den Hove a,c , J. Prickaerts a , J.L. Pawluski a,b, * a School for Mental Health and Neuroscience, Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands b GIGA-Neurosciences, University of Lie`ge, Belgium c Molecular Psychiatry, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany 1. Introduction Currently, it is well accepted that neural plasticity in the central nervous system (CNS) is one of the fundamental mechanisms that underlies memory formation. The most important brain structure in the encoding, consolidation and retrieval of memories is the hippocampus (Nadel, 1987; Scoville and Milner, 2000). Various forms of memory, such as spatial memory, rely on the functioning of the hippocampus and can be influenced by various factors like stress and elevated levels of corticosterone (Shors, 2001; Spanswick et al., 2007). The hippocampus is sensitive to changes in corticosterone levels in response to stress. This stress effect is evidenced by changes in neurogenesis (Gould et al., 1991; Mirescu and Gould, 2006), dendritic morphology, learning and memory (Magarinos and McEwen, 1995a,b; McEwen, 1999). In fact, several weeks of chronic stress, or repeated injections of high levels of corticosterone, causes atrophy in the apical dendrites of the pyramidal neurons in the CA3 region of the Ammon’s horn in male rats (Galea et al., 1997; Gould et al., 1990a; Luine et al., 1993; Magarinos and McEwen, 1995b; Watanabe et al., 1992b; Woolley et al., 1990b); and severe stress can also cause an overall reduction in the size of the hippocampus (Bodnoff et al., 1995; Coburn-Litvak et al., 2004; Magarinos et al., 1997; Sapolsky et al., 1985; Watanabe et al., 1992a,b; Woolley et al., 1990a). However, to date, very little is known about the effects of moderately elevated levels of glucocorticoids on dendritic mor- phology in the CA3 region of the hippocampus. In addition, it has been well documented that corticosterone plays an important role in hippocampal neurogenesis (Brummelte and Galea, 2010; Gould et al., 1992; McEwen and Gould, 1990; Mirescu and Gould, 2006; Mirescu et al., 2006). For example, acute or chronic stress consistently results in decreased hippocampal neurogenesis in adult males. Interestingly, preventing the eleva- tion of corticosterone levels during aging increases hippocampal neurogenesis in aged rats (Montaron et al., 2006). Previous work has also shown that adrenalectomy, and thus very low levels of corticosterone, has a beneficial effect on hippocampal neurogen- esis (Cameron and Gould, 1994; Montaron et al., 1999; Spanswick et al., 2011; Wong and Herbert, 2005). Others have also shown that corticosterone replacement to adrenalectomized animals, that Journal of Chemical Neuroanatomy 48–49 (2013) 23–28 A R T I C L E I N F O Article history: Received 12 September 2012 Received in revised form 8 January 2013 Accepted 8 January 2013 Available online 16 January 2013 Keywords: Dentate gyrus Plasticity Stress Neurogenesis HPA A B S T R A C T Plastic changes in the adult mammal hippocampus can be altered by many factors and perhaps the most well-documented is stress. Stress and elevated corticosterone levels have been shown to decrease hippocampal neurogenesis and decrease the complexity of CA3 pyramidal neurons. However, the extent of these changes in relation to low and moderately elevated levels of corticosterone has yet to be fully investigated. Therefore, the aim of the present study was to determine how low to moderately elevated circulating corticosterone levels affect dendritic morphology of CA3 pyramidal cells and hippocampal neurogenesis in adult male rats. To do this, three groups of adult male Wistar rats were used: (1) Sham- operated, (2) Adrenalectomized (ADX), and (3) ADX + corticosterone replacement. Primary results show that adrenalectomy, but not moderately elevated levels of corticosterone replacement, resulted in significant atrophy of CA3 pyramidal neurons. Interestingly, moderate corticosterone replacement resulted in significantly more surviving new cells in the dentate gyrus when compared to sham controls. This work shows that circulating levels of corticosterone differentially affect plasticity in the CA3 region and the dentate gyrus. ß 2013 Elsevier B.V. All rights reserved. * Corresponding author at: Department of Neuroscience, Maastricht University, Universiteitssingel 40, 6200 ER Maastricht, The Netherlands. Tel.: +31 043 388 1843; fax: +31 043 3884086. E-mail addresses: j.pawluski@maastrichtuniversity.nl, pawluski@gmail.com (J.L. Pawluski). Contents lists available at SciVerse ScienceDirect Journal of Chemical Neuroanatomy jo ur n al ho mep ag e: www .elsevier .c om /lo cate/jc h emn eu 0891-0618/$ – see front matter ß 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jchemneu.2013.01.001