Expression of heparanase 1 and heparanase 2 at the hippocampus

Abstract

Learning and memory processes are controlled by selective modification (weakening or strengthening) of synaptic connections between neurons within the hippocampal circuit, we found neuronal expression of heparanase-1 (hpa1) by both immunohistochemistry and in-situ hybridization. Western blot analysis of neuronal secretions however revealed the pro-form, i.e. proheparanase could trigger AMPA receptor internalization and thus impact on synaptic strength and long-term potentiation of synaptic efficacy. We further found not only heparanase-1 but also heparanase-2 (hpa2) expression in hippocampal neurons. We hypothesize therefore a partnership of hpa2 with hpa1 in regulating AMPA receptor internalization at glutamatergic synapses Immunohistochemical staining of hippocampal sections from adult rats found hpa2 expression in neurons of both the hippocampal DG, CA3 and CA1 regions. Like hpa1, hpa2 immunopositivity was found mainly in perinuclear regions of neurons. In addition to proheparanase, hpa2 was also found to be secreted by hippocampal neurons in culture. Secreted proheparanase and hpa2 remained associated with cell surface heparan sulfate. With results that support our hypothesis, we expect to pursue the partnership between proheparanase 1 and hpa2 with the respective recombinant protein.