68. Exposure to maternal prenatal depression predicts offspring inflammation at 25years

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  • are still ongoing. Potentially, this interdisciplinary project could con-tribute to an understanding of the extensive significance of thenewly discovered, intriguing world of the intestinal microbiota,including the gut-brain-axis.

    http://dx.doi.org/10.1016/j.bbi.2014.06.085

    66. Environmental conditions perceived by the brain alter CD8+ Tcells responsesM.M. Canali, J.A. Soria, M. Guyot, E. Murris, D. Daudlarian, J. Chabry,E. Mougneau, P. Blancou, N. Glaichenhaus

    660, Route des Lucioles, Institut de Pharmacologie Molculaire etCellulaire, CNRS, INSERM, Universit de Nice-Sophia Antipolis, Valbonne,PACA 06600, France

    We are interested in elucidating how the brain controls theimmune system. To this aim, we have established and validated anenvironmental enriched (EE) paradigm in which C57BL/6 mice expe-rience higher levels of sensory, motor, social, and cognitive stimuli,compared to animals housed in a standard environment (SE). Inagreement with previous studies, we found that EE increased hippo-campal neurogenesis and synaptogenesis, decreased anxiety andincreases exploratory activity. EE housing did not result in grossalterations in the frequency of neutrophils, dendritic cells (DC), mac-rophages, T cells and B lymphocytes in immunologically nave ani-mals. In contrast, upon immunization with ovalbumin (OVA), thenumber of OVA-specific CD8+ T cells in spleen was higher in EE micecompared to SE mice. Because the activation of CD8+ T cells is knownto be dependent on antigen cross-presentation by lymphoid CD8+DCs, we compared the phenotype of these DCs in SE and EE miceand found that lymphoid CD8+ DCs from EE mice expressed reducedlevels of PD-L1, a molecule that regulate the activation of CD8+ Tcells. PDL-1 down-regulation in EE mice was associated with alteredserum levels of corticosterone, therefore providing a possible linkbetween the environment, the HypothalamoPituitaryAdrenal(HPA) axis and DC function. Altogether, our results suggest that envi-ronment conditions could impact adaptive immune responses andtherefore the ability of the host to deal with pathogens.

    http://dx.doi.org/10.1016/j.bbi.2014.06.086

    67. The AMP-kinase inhibitor metformin inhibits chemotherapy-induced peripheral neuropathyQ. Mao-Ying a, A. Kavelaars a, K. Krukowski a, X. Huo a, T.J. Price b,C. Cleeland a, C.J. Heijnen a

    aUniversity of Texas MD Anderson Cancer Center, Neuroimmunology ofCancer Related Symptoms (NICRS) Laboratory, Department of SymptomResearch, 1400 Pressler Street, Unit 1450, Houston, TX 77030, USAbUniversity of Dallas, TX, USA

    Chemotherapy-induced peripheral neuropathy (CIPN) character-ized by loss of sensory sensitivity and pain in hands and feet is themajor dose-limiting toxicity of many chemotherapeutics. There areno FDA-approved treatments for CIPN. The anti-diabetic drug met-formin inhibits pathological pain following nerve injury in miceand rats. We tested the hypothesis that metformin protects againstchemotherapy-induced neuropathic pain and sensory deficits inmice. Mice were treated with cisplatin together with metformin orsaline. Co-administration of metformin almost completely preventedthe cisplatin- and paclitaxel-induced mechanical allodynia. Cisplatindecreased the time to detect an adhesive patch on the hind paw, anovel indicator of sensory deficits. Reduced sensory function was

    prevented by co-administration of metformin. Moreover, metforminprevented cisplatin-induced loss of IENFs in the hind paw. In thespinal cord, metformin treatment altered glial activation, indicatinga contribution of regulation of neuroinflammation to the protectiveeffect. In conclusion, metformin protects against pain and loss ofsensory function in a mouse model of CIPN. The mechanism involvesreduced peripheral nerve damage and changes in neuroinflamma-tion, strongly suggesting that metformin exerts a neuroprotectiveeffect. Because metformin is widely used for treatment of type II dia-betes, has a broad safety profile and is currently being tested as anadjuvant drug in cancer treatment, clinical translation of these find-ings could be rapidly achieved.

    http://dx.doi.org/10.1016/j.bbi.2014.06.087

    68. Exposure to maternal prenatal depression predicts offspringinflammation at 25 yearsD.T. Plant, S. Pawlby, C.M. Pariante

    Institute of Psychiatry, Kings College London, 2-059 James Black Centre,125 Coldharbour Lane, London SE5 9NU, UK

    Psychosocial adversity, such as childhood maltreatment, is asso-ciated with adulthood inflammation and depression. Elevated mark-ers of inflammation are routinely observed amongst depressedpatients. However, there is limited research into the effects of veryearly life adversity (i.e. exposure to depression in utero) on inflam-mation. In this study we investigate the impact of exposure tomaternal prenatal depression on offspring adulthood inflammation.The sample comprised 103 participants from the South London ChildDevelopment Study. A prospective longitudinal design wasemployed. Data on offspring exposure to maternal prenataldepression (20 and 36 weeks gestation), adulthood high sensitivityC-reactive protein levels (25 years) and adulthood depression(1825 years) was attained through one-to-one clinical assessments.Analysis revealed that exposure to maternal prenatal depression wassignificantly associated with clinically elevated levels of C-reactiveprotein (P3.0 mg/L) amongst non-depressed offspring at 25 years(OR = 5.9, 95% CI 1.327.7, p = .029). These findings demonstrate anovel association between prospectively assessed exposure tomaternal depression during gestation and elevated inflammation at25 years. Moreover, they suggest that these effects are independentto the influence of concurrent adulthood depression. Inflammationmay be a key mechanism for the biological embedding of intergen-erational stress transmission.

    http://dx.doi.org/10.1016/j.bbi.2014.06.088

    69. Endocannabinoid alterations in interferon-alpha induceddepressionZ. Zajkowska, A. Cattaneo, P.A. Zunszain, N. Hepgul, A. Russell,A. Borsini, C.M. Pariante

    Institute of Psychiatry, Kings College London, Stress, Psychiatry andImmunology (SPI) Lab, Department of Psychological Medicine, 125Coldharbour Lane, London SE5 9NU, Great Britain and Northern Ireland,UK

    Current treatment for chronic hepatitis C (HCV) viral infection,interferon-a (IFN-a), has been shown to induce depression in morethan 30% of patients. We investigated whether genes belonging tothe endocannabinoid (eCB) system are involved in mechanismsunderlying depression development. We recruited 50 HCV patientsreceiving IFN-a treatment and assessed them at treatment weeks

    e20 Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1e52

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