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  • Publication in Biological Psychiatry: Genome-wide DNA Methylation Changes in a Mouse Model of Infection-Mediated Neurodevelopmental Disorders.

    Epidemiological studies and translational work in animal models highlight that prenatal exposure to infectious or inflammatory insults can increases the risk of neurodevelopmental disorders such as schizophrenia, autism and bipolar disorder. Despite extensive findings supporting this association, the underlying molecular mechanisms still remain unknown. Using a well-established mouse model of prenatal viral-like immune activation, Juliet Richetto and collaborators demonstrate for the first time that this pathological association involves genome-wide DNA methylation differences at single nucleotide resolution in the prefrontal cortex.

    These findings, recently published in Biological Psychiatry, highlight that these long-term epigenetic modifications are a plausible mechanism underlying disease-risk in subjects with prenatal infectious histories.

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  • Publication in Cerebral Cortex: Genome-Wide Transcriptional Profiling and Structural Magnetic Resonance Imaging in the Maternal Immune Activation Model of Neurodevelopmental Disorders.

    Prenatal exposure to infectious or inflammatory insults is increasingly recognized to play an important role in the etiology neurodevelopmental disorders, such as schizophrenia, autism and bipolar disorder. The molecular processes underlying this pathological association, however, are only partially understood, and the majority of the experimental attempts to answer this question are hypothesis-driven investigations that may mask the discovery of novel disease mechanisms. Using a well-established mouse model of prenatal viral-like immune activation, Juliet Richetto and collaborators demonstrate, with a multi-system unbiased approach, that prenatal viral-like immune activation causes myelin-related transcriptional and epigenetic changes in corticostriatal areas.

    These findings, recently published in Cerebral Cortex, may provide a molecular mechanism whereby prenatal infection can impair myelin functionality and stability, ultimately concurring to the brain and behavioral alterations observed in neurodevelopmental diseases.

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  • Publication in International Journal of Molecular Sciences: DNA Damage and Repair in Schizophrenia and Autism: Implications for Cancer

    Psychiatric diseases with neurodevelopmental origins, such as schizophrenia and autism spectrum disorder (ASD), are associated with tremendous socioeconomic burden. Additionally, patients with ASD and schizophrenia often develop a variety of other disturbances, one of which is cancer. A growing body of evidence indicates that polymorphisms in DNA repair genes, which can lead to the accumulation of DNA damage in the central nervous system, are implicated in the aetiopathogenesis of these disorders. Strikingly, DNA repair gene polymorphisms are also implicated in cancer development. Enni Markkanen und Urs Meyer (in collaboration with Grigory Dianov at the University of Oxford) summarize the current evidence on cancer comorbidity in these brain disorders and discuss the putative involvement of oxidative stress, DNA damage and DNA repair in the aetiopathology of ASD and schizophrenia.

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  • Publication in Molecular Psychiatry: Transgenerational Transmission and Modification of Pathological Traits Induced by Prenatal Immune Activation

    Prenatal exposure to inflammatory insults is increasingly recognized to contribute to the etiology of neurodevelopmental pathologies like schizophrenia, autism and bipolar disorder. It remained unknown, however, if such immune-mediated brain anomalies can be transmitted to subsequent generations. By using an established mouse model of prenatal infection, Ulrike Weber-Stadlbauer and collaborators showed for the first time that prenatal immune activation can negatively affect brain and behavioral functions in multiple generations. These findings, recently published in Molecular Psychiatry, highlight a novel pathological aspect of this early-life adversity in shaping disease risk across generations.

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  • Publication in Cancer Cell: Targeting BRCA1 and BRCA2 deficiencies with G-quadruplex-interacting compounds

    G-quadruplexes are structures formed in nucleic acids by sequences that are rich in guanine. Four guanine bases can associate to form a square planar structure called a guanine tetrad, and two or more guanine tetrads can stack on top of each other to form a G-quadruplex. Enni Markkanen contributed to a recent study published in Cancer Cell showing that compounds that stabilize such G-quadruplex structures provide a promising pharmacologic tool to treat certain cancer cells. A defect in homologous recombination, for example due to mutations in the breast cancer genes BRCA1 or BRCA2, sensitizes cancer cells to G-quadruplex-interacting drugs.

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