P.1.08 Differential immune response to maternal separation stress in male and female prenatally-stressed juvenile rats

Molecular neuropsychopharmacology P.1.08 Differential immune response to maternal separation stress in male and female prenatally-stressed juvenile rats L. Desbonnet1 ° , D.L.A. van den Hove2 , A.M. Myint3 , B.E. Leonard4 , H.W.M. Steinbusch5 . 1 Royal College of Surgeons in Ireland, Molecular and Cellular Therapeutics, Dublin, Ireland; 2 Maastricht University, Dept. Neuroscience Faculty of Health Medicine and Life Sciences, Maastricht, The Netherlands; 3 University of Munich, Department of Psychiatry, Munich, Germany; 4 National University of Ireland Galway, Pharmacology Department, Galway, Ireland; 5 Maastricht University, Department of Psychiatry and Neuropsychology, Maastricht, The Netherlands Purpose of the study: It is well established that manipulations of the early environment, such as those induced by maternal stress during pregnancy and postnatal maternal separation can directly affect the developing nervous system, giving rise to abnormal developmental alterations in the offspring. Pro-inflammatory cytokines are the most important humoral mediators of the host defence system and are also involved in the behavioural and physiological responses to acute stress exposure. Changes in the plasma levels of pro-inflammatory cytokines have been associated with the development of psychopathological illnesses such as depression [1] and schizophrenia [2]. Sexual dimorphisms with respect to the effects of PS on behaviour and the immune system have also been reported. Despite this, the majority of research in the area of prenatal stress has focused primarily on male offspring. In the present study we investigated the effects of prenatal restraint stress on the peripheral and central pro-inflammatory cytokine responses to an acute postnatal maternal separation stress in juvenile rats. An additional aim was to determine whether male and female immune responses differ following exposure to stress in infancy. Methods: Pregnant Fischer-344 rats were restrained and exposed to a bright light for a period of 45 minutes, three times daily (9.00 a.m., 1.00 p.m., 5.00 p.m.) during the last week of gestation (embryonic days 14−21). Control dams were left undisturbed in their home-cages for this period. At postnatal day 21, 20 males (10 = prenatally stressed, 10 = control) and 20 females (10 = prenatally stressed, 10 = control) were separated from their mothers for a 30 minute period. A maximum of two male and two female rat pups from each litter of control and prenatally-stressed groups were used. Concentrations of the pro-inflammatory cytokines IL-1b and TNF-a, and the anti-inflammatory cytokine IL-10 were measured using commercially available Duoset ELISA (R&D

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Systems, Minneapolis MN) from whole blood cultures and dissected brain areas (frontal cortex, hippocampus and subventricular zone). Results: Concentrations of IL-1b, TNF-a, and IL-10 were increased in the blood of prenatally-stressed male offspring and decreased in the subventricular zone of prenatally-stressed females relative to controls (P < 0.05). IL-10 and IL-1b levels were also significantly reduced in the hippocampus of prenatally-stressed female offspring in response to maternal separation stress (P < 0.05). Conclusions: The results indicate that at this point in development prenatal stress induces a sexually-dimorphic immune response to maternal separation stress in rat offspring, which reinforces the importance of gender when considering the effects of stress on immune system development. Furthermore, the selective effects of prenatal stress on cytokine concentrations in the subventricular zone and hippocampus of female prenatally stressed offspring may have important implications for brain plasticity and susceptibility to psychopathological disorders such as depression and schizophrenia in adulthood. Reference(s) [1] Maes, M., 1995, Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry 19: 11−38. [2] Fan, X., Goff, D.C., Henderson, D.C., 2007, Inflammation and schizophrenia. Expert Rev Neurother 7: 789–796. P.1.09 Sarizotan stimulates cell proliferation in neurogenic regions in experimental Parkinsonism M. Egeland1 ° , X. Zhang1 , P. Svenningsson1 . 1 Karolinska Institute, Pharmacology and Physiology, Stockholm, Sweden Sarizotan was developed as a potential atypical antipsychotic pharmacologically exhibiting high affinities to the serotonin 5-HT1A receptor, acting as an agonist, and furthermore to the dopamine D2-like (D4, D3 and D2) receptors, acting as an antagonist. Studies in animal models of Parkinsonism revealed that sarizotan has antidyskinetic properties and could represent a new approach for the treatment of extrapyramidal motor complications in Parkinson’s disease [1]. Reductions of cell-proliferation related to neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the dentate gyrus (DG) have been found in Parkinson’s patients as well as experimental