Brain heparanase expression is up-regulated during postnatal development and hypoxia-induced neovascularization in adult rats

• Published in: Journal of neurochemistry 2008-04, Vol.105 (1), p.34-45
• Main Authors: Navarro, Fabrice P, Fares, Raafat P, Sanchez, Pascal E, Nadam, Jérémie, Georges, Béatrice, Moulin, Colette, Morales, Anne, Pequignot, Jean-Marc, Bezin, Laurent
• Format: Article
• Language: English
• Subjects: Age Factors; Analysis of Variance; angiogenesis; Animals; Animals, Newborn; Antigens, CD34 - metabolism; Biochemistry; Biological and medical sciences; Brain; Brain - enzymology; Brain - growth & development; Bromodeoxyuridine - metabolism; Cell Differentiation - drug effects; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; Disease Models, Animal; Environment; environmental enrichment; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - physiology; Glucuronidase - genetics; Glucuronidase - metabolism; hippocampus; Hypoxia; Hypoxia - complications; Ischemic Preconditioning - methods; Life Sciences; Male; Medical sciences; neocortex; Neovascularization, Pathologic - etiology; Neovascularization, Pathologic - pathology; Nerve Growth Factor - pharmacology; Neurology; neuronal differentiation; Other; PC12 Cells; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Rodents; Tumors; vascular endothelial growth factor; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2007.05116.x

Heparanase is an endo-β- d-glucuronidase which specifically cleaves extracellular and cell surface heparan sulphates at intra-chain sites. Its enzymatic activity is strongly implicated in cell dissemination associated with tumor metastasis and inflammation. Indeed, heparanase gene is expressed in various tumors and its over-expression is correlated with increased tumor vascularity and metastatic potential of tumor cells. However, heparanase expression in non-invasive and non-immune tissue, including brain, has received less attention. Using RT-qPCR, western blot and histological analysis, we demonstrate in the adult rat that heparanase transcript is differentially expressed according to brain area, and that heparanase protein is mainly detected in neurons. Furthermore, we provide evidence that heparanase transcript and protein reach their greatest levels at early postnatal stages, in particular within the neocortex characterized by intensive structural plasticity. Using the in vitro model of PC12-induced neuronal differentiation, we suggest that developmental regulation of heparanase may coincide with axonal and dendritic pathfinding. At adulthood, we demonstrate that the increased heparanase transcript level correlates in the hippocampus with enhanced angiogenesis following repeated hypoxia exposures. Taken together, our results emphasize the potential importance of heparanase in brain homeostasis, both during development and adaptative responses to severe environmental challenges.