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• W2944671146 abstract "P75 neurotrophin receptor (NTR) plays a pivotal role in various tissues including the central nervous system (CNS). Through binding its ligands, it exerts versatile functions, implicated in both neurodegeneration and regenerative events. Besides various categories of stem cells, it is considered as a prototype marker of Schwann cell-like brain glia, a unique type of macroglia, which has been referred to as aldynoglia. In fact, in the peripheral nervous system (PNS) all Schwann cell lineages express p75NTR with the exception of mature myelinating Schwann cells. Failure of remyelination is the major drawback in many neurodegenerative pathologies of the CNS, although various animal models suggest substantial endogenous glial reponses implied in neuroregeneration and remyelination, respectively. Interestingly, recent reports suggest that centrally derived Schwann cells may significantly contribute to regenerative events following CNS injury, especially under conditions of astrocytic loss. Though extensively characterized in the CNS of different species, knowledge on the role of p75NTR in the CNS with special emphasis to Schwann cell like brain glia is sparse. The aim of this thesis was to i) summarize the current knowledge on aldynoglial p75NTR expression with special regard to a canine model for demyelinating disease, and ii) to elucidate the role of p75NTR in glial cells of the murine CNS in vitro. The present thesis additionally details iii) p75NTR immunoreactivity in age-related granular hippocampal deposits of SJL/J mice. Organotypic cerebrum and brain stem slices of adult mice were cultivated for up to 18 days in vitro and investigated by means of immunohistochemistry and in situ hybridization, respectively. Cultivation of slices was associated with a progressively increasing spontaneous occurrence of bi- to multipolar p75NTR-positive, but periaxin-negative glia, indicative of aldynoglial Schwann cell-like cells, which strikingly correlated to neuronal loss of p75NTR expression and a remarkable response of CD107b positive microglia/macrophages. A certain population of bi- to multipolar cells expressed GAP-43, a marker for neuroaxonal regeneration and immature Schwann cells, respectively. A comparatively more intense response of macrophages/microglia and a higher number of bi- to multipolar p75NTR-positive glia were found in brain stem slices compared to cerebrum slices. This thesis additionally reports Periodic acid-Schiff (PAS) positive granular deposits in the hippocampus of SJL mice, a strain not reported to be prone to this phenomenon before. Such age-related granular deposits, commonly organized in clusters, have been reported in other mouse strains and share characteristics of polyglucosan bodies. In the present study, PAS positive granular deposits developed with aging in cornu ammonis (CA)1 and CA2 regions of the hippocampus. Interestingly, the granules stained intensely positive with a polyclonal antibody against p75NTR. These clusters of granular deposits significantly diminished in number in brains of mice from an unrelated experiment, which were previously treated with cuprizone, a copper chelator used as a demyelinating agent. Taken together, the in vitro investigations highlight the role of microglia/macrophages, which seem to be an important triggering factor, facilitating the occurrence of p75NTR positive macroglia and substantiate organotypic slice cultures as an appropriate model to address the role of this unique type of potentially regeneration-promoting macroglia. The in vivo part of the present thesis is the first report that demonstrates that i) age-related PAS positive hippocampal granules occur in SJL mice, ii) their diminished occurrence following cuprizone treatment, and iii) their immunoreactivity for p75NTR. The decline of PAS positive clusters following cuprizone treatment supports the idea that the formation of PAS-positive granules in the senescent mouse brain might be the result of the imbalance of redox-active metals such as copper and iron, and/or a dysregulation of complementary mechanisms that regulate their homeostasis in astrocyte-neuron coupling, respectively. It remains to be determined whether the unsuspected immunoreactivity for p75NTR represents a false positive reaction or if p75NTR is in fact involved in the pathogenesis of age-related hippocampal granular deposits in mice." @default.
• W2944671146 created "2019-05-16" @default.
• W2944671146 creator A5016571088 @default.
• W2944671146 date "2014-01-01" @default.
• W2944671146 modified "2023-09-26" @default.
• W2944671146 title "In vivo and in vitro characterization of p75 neurotrophin receptor expressing cells and their origin in the murine central nervous system" @default.
• W2944671146 hasPublicationYear "2014" @default.
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