Abstract
The molecular mechanisms underlying neuronal plasticity, i.e. the capacity of the brain to continuously adapt its structural organization to new situations, remain largely unknown. In this thesis, we explored functional aspects of two proteins that presumably play a role in neuronal plasticity, namely the serine protease inhibitor neuroserpin and the brain-derived neurotrophic factor BDNF. In our studies, we have used the neuroendocrine intermediate pituitary melanotrope cells of the amphibian Xenopus laevis as a model system. These cells exert plasticity at both the cellular and neuronal level; in vivo they are responsible for the process of background adaptation of Xenopus by regulating the release of the proopiomelanocortin (POMC)-cleavage product alpha-melanophore stimulating hormone, which causes pigment dispersion in skin melanophores. First, neuroserpin mRNA and protein were primarily expressed in neuronal and neuroendocrine tissues in Xenopus. In addition, the expression of neuroserpin was linked to melanotrope cell activation. To perform in vivo studies on the physiological role of neuroserpin, we generated transgenic Xenopus with melanotrope cell-specific overexpression of neuroserpin. In these animals the structure of the extracellular matrix (ECM) of the melanotropes was affected, implying a role for neuroserpin as a serine protease inhibitor in the ECM. Secondly, to investigate aspects of the role of BDNF in plasticity, we generated transgenic Xenopus with melantrope cell-specific overexpression of BDNF. In transgenic Xenopus with overexpression of mature BDNF, we observed in the pituitary of these animals the formation of a nodule consisting of glial cells and axons of which a significant part was myelinated. Thus, mature BDNF may induce glial cell proliferation and axonal outgrowth and myelination, and as such is involved in neuronal plasticity. In conclusion, the results described in this thesis enhance our understanding of the physiological roles of neuroserpin and BDNF in neuroendocrine and neuronal plasticity. A better understanding of the complex molecular mechanisms underlying plasticity will ultimately improve our knowledge of brain functioning in health and disease.
