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Cerebral Cortex Advance Access published online on December 10, 2008
Cerebral Cortex, doi:10.1093/cercor/bhn225
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© 2008 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats

Yanhua Lin1,2, Gert J Ter Horst1, Romy Wichmann1, Petra Bakker1, Aihua Liu3, Xuejun Li2 and Christel Westenbroek1

1 Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9700 RB Groningen, the Netherlands, 2 Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural and Biomimetic Drugs, 3 The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China

Address Correspondence to Prof Gert J Ter Horst, Department of Neuroscience, University Medical Center Groningen and University of Groningen, Graduate School of Behavioral and Cognitive Neurosciences, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, the Netherlands. Email: g.j.ter.horst{at}med.umcg.nl.

Studies show that sex plays a role in stress-related depression, with women experiencing a higher vulnerability to its effect. Two major targets of antidepressants are brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element–binding protein (CREB). The aim of this study was to investigate the levels of CREB, phosphorylation of CREB (pCREB), and BDNF in stress-related brain regions of male and female rats after stress and recovery. CREB and pCREB levels were examined in CA1, CA2, CA3, paraventricular nucleus of the thalamus (PVT), amygdala, anterior cingulate area, dorsal part (ACAd), and infralimbic area of prefrontal cortex (PFC), whereas dentate gyrus (DG) and prelimbic area (PL) of PFC were examined for BDNF levels. Our results demonstrate that levels of CREB and pCREB in male CA1, CA2 and CA3, PVT, amygdala, and ACAd were reduced by stress, whereas the same brain regions of female rats exhibited no change. BDNF levels were decreased by chronic stress in female PL but were increased by acute stress in female DG. BDNF levels in male DG and PL were found not to undergo change in response to stress. Abnormalities in morphology occurred after chronic stress in males but not in females. In all cases, the levels of CREB, pCREB, and BDNF in recovery animals were comparable to the levels of these proteins in control animals. These findings demonstrate a sexual dimorphism in the molecular response to stress and suggest that these differences may have important implications for potential therapeutic treatment of depression.

Key Words: depression • neuroplasticity • recovery • sex differences • stress response


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