42. The mood stabilizer valproic acid down regulates neuronal cyclooxygenase-2 expression: Central role of nuclear factor- kappa B after long-term, but not short-term treatment Vikramjeet Singh a , Francisco J. Caballero b , Marco A. Calzado b , Eduardo Candelario-Jalil a,c , Friederike von Müller a , Caroline Ottomeyer a , Michael Hüll a , Eduardo Munoz b , Klaus Lieb a,d , Bernd L. Fiebich a a Department of Psychiatry, University Medical Center Freiburg, Hauptstr. 5, D-79104 Freiburg, Germany b Departamento de Biologı ´a Celular, Fisiologı ´a e Inmunologı ´a, Univers- idad de Córdoba, Avda Menendez Pidal s/n. 14004, Córdoba, Spain c Department of Neurology, University of New Mexico, Albuquerque, NM 87131, USA d Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, D-55131 Mainz, Germany The mechanisms of action of mood stabilizing substances have not been elucidated sufficiently so far. Recent data suggested that mood stabilizers such as valproic acid (VPA) and lithium interfere with the synthesis of prostaglandins (PG) which depend on phos- pholipase A2 and cyclooxygenase (COX) activity. Here we investi- gated whether VPA is able to inhibit COX-2 synthesis and prostaglandin E2 (PGE2) release in neuronal cell lines and which molecular mechanisms are underlying these effects. During the studies, we found that VPA dose-dependently inhibited IL-1b- induced PGE2 release after treatment of cell cultures for 30 min, 3 and 7 days. This inhibition was paralleled by a dose-dependent reduction of COX-2 mRNA and protein synthesis after 3 and 7 days, but not after 30 min, indicating a distinct molecular mecha- nism during short- and long-term treatment. Further more we worked to anticipate this time dependent regulation of PGE2 and COX-2 and found that Short-term effects of VPA were medi- ated by a dose-dependent inhibition of isoprostane synthesis pointing to interference in the arachidonic acid cascade upstream of COX-2, whereas long-term effects involved transcriptional regu- lation of COX-2 expression. Long-term treatment with VPA and sodium butyrate inhibited IL-1b-induced COX-2 gene transcription, nuclear factor kappaB (NF-jB)-DNA binding activity and IkappaB alpha (IjBa) phosphorylation. Moreover, inhibition of IkappaB kinase (IKK2) by SC514 completely mimicked VPA effects indicat- ing a central role of NF-jB in the long-term effects of VPA on COX-2 expression and PGE2 synthesis. Our present results can help to develop COX-2 inhibitors in the treatment of bipolar disorders and possibly can demonstrate the implication of COX and PGs in the etiopathology and treatment of these disorders. doi:10.1016/j.bbi.2009.05.045 43. Effects of mindfulness-based coping with university life (mbcul): A pilot study Ms. Siobhan Lynch, Marie-Louise Gander, Niko Kohls, Brigitte Kudielka, Harald Walach School of Social Sciences and Samueli-Institute, European Office, Univer- sity of Northampton, Boughton Green Road, Northampton NN2 7AL, UK University life is accompanied by an array of potential stressors, such as chan-ging relationships, new living environments and aca- demic pressure. Additionally, the mental health of students appears to be on the decline. An 8-week course of mindfulness-based coping with university life (MBCUL) has been developed to help students cope with the stressors of university life, based on Kabat-Zinn’s mindfulness-based stress reduction program. The primary objectives were to test the feasibility of this study and whether MBCUL improves mindfulness. Secondary we investigated its impact on mental health and on the stress system via the hypothalamus–pitu- itary–adrenal (HPA) and the sympathic-adrenal-system (SNS). The study is a pre/post-intervention design. Psychological and physio- logical measurements were taken: mindfulness (FMI), mood (HADS), stress (PSS), s-cortisol for HPA and s-alpha-amylase for SNS. We were interested in the change of the cortisol awakening response (CAR) as well as the change of the diurnal profile of the s-cortisol and s-alpha-amylase. Data was collected from 11 MBCUL and from 8 wait-list-control participants. The saliva from 8 MBCUL and 6 con- trol-group participants was used our analysis. There was a sig. change of FMI (z = À2.437, p < 0.015), HADS (z = À2.243, p < 0.025) and PSS (z = À2.374, p < 0.018). We observed a sig. negative correla- tion between the change of FMI and the change in PSS (rho = À0.744, n = 10, p < 0.014) and HADS (rho = À0.861, n = 9, ph0.003). A trend could be seen in a change from a slightly flatter to a steeper CAR- curve and an overall lower diurnal profile of cortisol and alpha-amy- lase. Due to the small number of participants we did not observe any sig. effects. MBCUL increased mindfulness and improved the stress- levels and mental health of students in this pilot study. At present we are replicating the study with a larger sample size. doi:10.1016/j.bbi.2009.05.046 44. Chronic social stress influences virus specific T-cell response to LCMV infection Annette Sommershof a , Harald Engler b , Marcus Groettrup a a Department of Biology/Immunology, University of Konstanz, Konstanz, Germany b Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, Essen, Germany Chronic stress has been known for many years to influence com- ponents of the innate and adaptive immune system, thereby altering the ability to defend the host against viral infections. This study investigated the effects of chronic social stress on virus-specific cyto- toxic T lymphocytes (CTL) response in socially stressed and non- stressed control mice after LCMV infection. To induce social stress in mice we used a well-established model of social stress termed social disruption stress (SDR). This stress procedure is based on the repeated social defeat experience of group-housed male mice induced by daily confrontation with an aggressive intruder mouse. We found that after six consecutive days of social stress the genera- tion of LCMV specific CTLs was significantly reduced in stressed mice compared to controls. More specifically, the response to the two immunodominant LCMV epitopes GP33 and NP396 were decreased whereas other epitopes were not affected. Additionally, we noted an approx. About 50% reduction in the serum levels of IFNg. Interest- ingly, these effects were only observed when SDR was applied prior to LCMV-infection, while there were only modest changes on LCMV- specific T-cell responses when SDR was applied concurrently with infection. We further found profoundly reduced numbers of acti- vated CD8+ T cells in case of a prolonged stress procedure, due to a diminished in vivo proliferation capacity as shown by BrdU incor- poration. These alterations were accompanied by significantly reduced expression of the early T cell activation marker CD69 in socially stressed mice. Taken together, our data imply that social stress is associated with a fundamental suppression of the functional capacities of T cells, which may represent a key factor in the increased susceptibility of socially stressed individuals to viral infections. doi:10.1016/j.bbi.2009.05.047 Abstracts / Brain, Behavior, and Immunity 23 (2009) S8–S23 S21