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Traumatic stress in early life is a strong risk factor for psychiatric disorders that can affect individuals across several generations. Although the underlying mechanisms have been proposed to implicate serotonergic transmission in the brain, the neural circuits involved remain poorly delineated. Using pharmacological functional magnetic resonance imaging in mice, we demonstrate that traumatic stress in postnatal life alters 5-HT receptor-evoked local and global functions in both, the exposed animals and their progeny when adult. Disrupted functional connectivity is consistent across generations and match limbic circuits implicated in mood disorders, but also networks not previously linked to traumatic stress. These findings underscore the neurobiology and functional mapping of transgenerational effects of early life experiences.

Aims/hypothesisNon-invasive diagnostic tools specific for pancreatic beta cells will have a profound impact on our understanding of the pathophysiology of metabolic diseases such as diabetes. The objective of this study was to use molecular imaging probes specifically targeting beta cells on human samples and animal models using state-of-the-art imaging modalities (fluorescence and PET) with preclinical and clinical perspective.MethodsWe generated a monoclonal antibody, 8/9-mAb, targeting transmembrane protein 27 (TMEM27; a surface N-glycoprotein that is highly expressed on beta cells), compared its expression in human and mouse pancreas, and demonstrated beta cell-specific binding in both. In vivo imaging was performed in mice with subcutaneous insulinomas overexpressing the human TMEM27 gene, or transgenic mice with beta cell-specific hTMEM27 expression under the control of rat insulin promoter (RIP-hTMEM27-tg), using fluorescence and radioactively labelled antibody, followed by tissue ex vivo analysis and fluorescence microscopy.ResultsFluorescently labelled 8/9-mAb showed beta cell-specific staining on human and mouse pancreatic sections. Real-time PCR on islet cDNA indicated about tenfold higher expression of hTMEM27 in RIP-hTMEM27-tg mice than in humans. In vivo fluorescence and PET imaging in nude mice with insulinoma xenografts expressing hTMEM27 showed high 8/9-mAb uptake in tumours after 72 h. Antibody homing was also observed in beta cells of RIP-hTMEM27-tg mice by in vivo fluorescence imaging. Ex vivo analysis of intact pancreas and fluorescence microscopy in beta cells confirmed these findings.Conclusions/interpretationhTMEM27 constitutes an attractive target for in vivo visualisation of pancreatic beta cells. Studies in mouse insulinoma models and mice expressing hTMEM27 demonstrate the feasibility of beta cell-targeted in vivo imaging, which is attractive for preclinical investigations and holds potential in clinical diagnostics.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-012-2605-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users.