Abstract
The extracellular matrix (ECM) of the central nervous system (CNS) is found dispersed in the neuropil or forming aggregates around the neurons called perineuronal nets (PNNs). The ECM mainly contains chondroitin sulphate proteoglycans (CSPG), hyaluronic acid (HA) and tenascin-R. Heparan sulphate proteoglycans (HSPG) can also be secreted in the ECM or be part of the cell membrane. Aquaporins (AQP) are a family of transmembrane proteins that act as water selective channels. AQP1 and AQP4 are widely expressed in the CNS where they play several roles. Nevertheless the importance of these elements, their distribution in the CNS of mice is only partially known.The histochemical distribution of PNNs, aggrecan, HA, HSPGs and AQP4 were semiquantitatively evaluated in the whole CNS of mice. The results showed that aggrecan, HA and HSPGs have a perineuronal distribution, and AQP4 has an heterogeneous distribution throughout the neuropil of the CNS. An inverse correlation between AQP4 and ECM components was observed, suggesting a complementary role in the maintenance of water homeostasis. A common location for AQP4 and HSPGs was also observed in CNS neuropil.
ECM and AQPs were studied in bovine spongiform encephalopathy (BSE) and Scrapie. Both diseases belong to the group of animal transmissible spongiform encephalopathies (TSE) or prion diseases. They are characterized by the accumulation of resistant prion protein (PrPres) in the CNS, neuronal loss, spongiform degeneration and glial cell proliferation.
The ECM was studied by immunohistochemistry in the transgenic mice boTg110, overexpresing bovine PrPc, intracranially infected with cattle BSE; and in C57BL/6 mice intraperitoneally infected with RML scrapie strain. Both of them showed dramatical ECM disturbances at latest stage of both diseases.
AQP1 and AQP4 were studied in boTg110 mice by immunohistochemistry, and in BSE field cases by immunohistochemistry and western blot. Both AQPs were overexpressed in the membrane of astrocytes at terminal stage of the disease in mice with evident clinical signs, and in pre-clinical cattle.
The ECM changes and AQPs overexpression were correlated with PrPres accumulation, and activated glial cells. Therefore we conclude that alterations in the ECM, AQP1 and AQP4 are a consequence of glial cell activation induced by PrPres, and both changes could lead to ion and water imbalance in the CNS which could contribute to trigger the typical histopathological features of TSEs.
| Date of Award | 29 Oct 2007 |
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| Original language | English |
| Supervisor | Anna Maria Bassols Teixido (Director) & Martí Pumarola Batlle (Director) |