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Adult motor neurons show increased susceptibility to axotomy-induced death in mice lacking clusterin.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
2005 In: European Journal of Neuroscience, ISSN 0953-816, Vol. 21, no 7, 2025-2028 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2005. Vol. 21, no 7, 2025-2028 p.
URN: urn:nbn:se:uu:diva-95210OAI: oai:DiVA.org:uu-95210DiVA: diva2:169338
Available from: 2006-11-27 Created: 2006-11-27Bibliographically approved
In thesis
1. Clusterin and Megalin in The Spinal Cord
Open this publication in new window or tab >>Clusterin and Megalin in The Spinal Cord
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nerve injury induces up-regulation of the chaperone protein clusterin in affected neurons and adjacent astrocytes but the functional significance of this response is unclear. We find that motor neuron survival is significantly greater in clusterin(+/+) compared to (-/-) mice. These results suggest that endogenous expression of clusterin is neuroprotective after nerve injury. However, motor neuron survival in clusterin overexpressing mice was not different from that in wildtype mice. In contrast, treatment of neuronal cultures with clusterin-TAT recombinant protein is neuroprotective, including a positive effect on neuronal network complexity.

Since extracellular clusterin complexes are endocytosed after binding to various receptors, we examined the expression of known clusterin binding receptors in the spinal cord. We find that megalin is expressed in the nuclei of two cell populations in the mouse spinal cord: i) oligodendrocytes in late postnatal and adult spinal cord white matter, and ii) transiently (E11-15) in a population of immature astrocytes in the dorsal spinal cord. We find no correlation between clusterin and megalin in the intact or injured spinal cord. However, intranuclear localization of megalin, suggesting signalling properties, is supported by the co-localization with γ-secretase, the enzyme responsible for endodomain cleavage of megalin. Megalin deficient mice display a pronounced deformation of the dorsal part of spinal cord, an almost complete absence of oligodendroglial progenitor cells, and a marked reduction in the population of mature astrocytes at later prenatal developmental stages.

Taken together, our findings indicate that megalin is a novel signalling molecule for distinct populations of glial cells in the pre- and postnatal spinal cord. The functional role(s) of megalin is unknown. However, its expression patterns and cellular localization suggest that megalin regulates differentiation of oligodendrocytes and astrocytes in the prenatal spinal cord, as well as the function of myelinating oligodendrocytes in the postnatal spinal cord.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 58 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 208
Neurosciences, nerve degeneration, hypoglossal nerve, chaperone, apolipoprotein, development, transcription factor, astrocyte, glial differentiation, myelin, cell signalling, Neurovetenskap
urn:nbn:se:uu:diva-7365 (URN)91-554-6739-3 (ISBN)
Public defence
2006-12-19, B22, Biomedical Centre (BMC), Husargatan 3, Uppsala, 13:15
Available from: 2006-11-27 Created: 2006-11-27 Last updated: 2013-05-23Bibliographically approved

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