Involving children and young people in clinical research through the forum of a European Young Persons' Advisory Group: needs and challenges.

Children and young people are seen as fundamental to the design and delivery of clinical research as active and reflective participants. In Europe, involvement of children and young people in clinical research is promoted extensively in order to engage young people in research as partners and to give them a voice to raise their own issues or opinions and for their involvement in planning and decision making in addition to learning research skills. Children and young people can be trained in clinical research through participation in young person advisory groups (YPAGs). Members of YPAGs assist other children and young people to learn about clinical research and share their experience and point of view with researchers, thereby possibly influencing all phases of research including the development and prioritization of research questions, design and methods, recruitment plans, and strategies for results dissemination. In the long term, the expansion of YPAGs in Europe will serve as a driving force for refining pediatric clinical research. It will help in a better definition of research projects according to the patients' needs. Furthermore, direct engagement of children and young people in research will be favorable to both researchers and young people.

Impaired hippocampal plasticity and altered neurogenesis in adult Ube3a maternal deficient mouse model for Angelman syndrome.

Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by mental retardation, seizures and sleep disturbances. It results from lack of the functional maternal allele of UBE3A gene. Ube3a maternal-deficient mice (Ube3a m-/p+), animal models for AS, are impaired in hippocampal-dependent learning tasks as compared with control (Ube3a m+/p+) mice. We first examined the basal expression of immediate early genes which expression is required for synaptic plasticity and memory formation. We found that basal expression of c-fos and Arc genes is reduced in the DG of Ube3a maternal deficient mice compared to their non-transgenic littermates. We then examined whether adult hippocampal neurogenesis, which likely serves as a mechanism toward brain plasticity, is altered in these transgenic mice. Neurogenesis occurs throughout life in mammalian dentate gyrus (DG) and recent findings suggest that newborn granule cells are involved in some forms of learning and memory. Whether maternal Ube3a deletion is detrimental on hippocampal neurogenesis is unclear. Herein, we show, using the mitotic marker Ki67, the birthdating marker 5-bromo-2'-dexoyuridine (BrdU) and the marker doublecortin (DCX) to respectively label cell proliferation, cell survival or young neuron production, that the Ube3a maternal deletion does not affect the proliferation nor the survival of newborn cells in the hippocampus. In contrast, using the postmitotic neuronal marker (NeuN), we show that Ube3a maternal deletion is associated with a lower fraction of BrdU+/NeuN+ newborn neurons among the population of surviving new cells in the hippocampus. Collectively, these findings suggest that some aspects of adult neurogenesis and plasticity are affected by Ube3a deletion and may contribute to the hippocampal dysfunction observed in AS mice.