SOBER 2 - Sex On Brain European Research 2 Effects of Gonadotropin Releasing Hormone Receptor blockage on brain development and behaviour

This study is designed to enhance our understanding of sex specific brain development during puberty and adolescence and its implication for the aging process of the brain. Gonadotropin Releasing Hormone receptor (GnRHR) blockage pauses not only reproduct ive ability, but may also have significant influence on non-reproductive brain areas. GnRH blockage has been applied in an animal model (sheep) to study sexually dimorphic traits related to brain function and morphology during puberty. A longitudinal ob servational cohort study was established, involving 96 lambs separated into four treatment groups (males/females, treated/controls). The lambs were assessed with a battery of neuropsychological/behavioural tests. At one year of age, in March 2009, the an imals were euthanized and tissues harvested for studies of metabolic/hormonal, and morphological/molecular endpoints. The first GnRHR blocked biobank worldwide was established in Oslo summer 2009. Our direct access to high-throughput techniques at the Ga ustad Neuroscience Network,industrial funding, strategic financing in 2009 to the SOBER group and the quality of the partners will guarantee the further steps of unravelling the different neuroendocrine components involved in brain development. The projec t combines basic science with clinical science in the expanding field of GnRH signaling, and may enable translation of basic neuroendocrinological knowledge into daily clinical decision making with regard to intervention in patients. Our preliminary res ults show direct effects of prepubertal GnRH receptor blockage on sex-specific cognitive and brain development, heart rate variability and motor activity. The experiments and analyses outlined in this proposal are designed to further explore these finding s and to understand the effects on brain morphology and function on cellular and sub-cellular levels. This grant will finance R&D costs in this highly technology driven first project of this kind worldwide.