Changes in neuroplasticity following early-life social adversities

Social adversities experienced in childhood can have a profound impact on the developing brain, leading to the emergence of psychopathologies in adulthood. Despite the burden this places on both the individual and society, the neurobiological aspects mediating this transition remain unclear. Recent advances in preclinical and clinical research have begun examining neuroplasticity-the nervous system's ability to form adaptive changes in response to new experience-in the context of early-life vulnerability to social adversities and plasticity-related alterations following such traumatic events. A key mediator of plasticity-related molecular processes is the brain-derived neurotrophic factor (BDNF), which has also been implicated in various psychiatric disorders related to childhood social adversities. Preclinical and clinical data suggest early-life social adversities (ELSA) might be associated with accelerated maturation of social network circuitry, a possible ontogenic adaptation to the adverse environment. Neural plasticity decreases by adulthood, lessening the efficacy of treatment in ELSA-related psychiatric disorders. However, literature data suggest that by increasing BDNF/TrkB signalling through antidepressant treatment a juvenile-like plasticity state can be induced, which allows for reorganization of the social circuitry when guided by psychotherapy and surrounded by a safe and positive environment

Rett syndrome – biological pathways leading from MECP2 to disorder phenotypes

Rett syndrome (RTT) is a rare disease but still one of the most abundant causes for intellectual disability in females. Typical symptoms are onset at month 6-18 after normal pre- and postnatal development, loss of acquired skills and severe intellectual disability. The type and severity of symptoms are individually highly different. A single mutation in one gene, coding for methyl-CpG-binding protein 2 (MECP2), is responsible for the disease. The most important action of MECP2 is regulating epigenetic imprinting and chromatin condensation, but MECP2 influences many different biological pathways on multiple levels although the molecular pathways from gene to phenotype are currently not fully understood. In this review the known changes in metabolite levels, gene expression and biological pathways in RTT are summarized, discussed how they are leading to some characteristic RTT phenotypes and therefore the gaps of knowledge are identified. Namely, which phenotypes have currently no mechanistic explanation leading back to MECP2 related pathways? As a result of this review the visualization of the biologic pathways showing MECP2 up- and downstream regulation was developed and published on WikiPathways which will serve as template for future omics data driven research. This pathway driven approach may serve as a use case for other rare diseases, too