Role of "neuronal" gap junction proteins in regulating post-natal hippocampal neurodegeneration and neurogenesis in vitro and in vivo

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Title: Role of "neuronal" gap junction proteins in regulating post-natal hippocampal neurodegeneration and neurogenesis in vitro and in vivo
Authors: Sorbara, Catherine D
Date: 2009
Abstract: Adult neural stem and progenitor cells (NPCs) are located within specific neurogenic niches, such as the subgranular zone of the dentate gyrus. Cell-cell communication through gap junction channels is believed to play an important role in embryonic neurogenesis. Connexins, the protein subunits of gap junctions, are expressed in NPCs and connexin36 (Cx36) is considered the prototypical neuronal connexin although a role in neurogenesis had yet to be assessed. Here, I examined the influence of Cx36 on NPC proliferation, specification, and survival in the hippocampus in vitro and in vivo in both wild type and Cx36-/- mice. Using cultured neurospheres from P0-P3 mice pup hippocampi, I show that Cx36 protein is first expressed upon engagement to a laminin matrix. Moreover, a Cx36 null mutation enhances neurogenesis under certain microenvironment conditions apparently by accelerating differentiation. Using thymidine analogs to label actively proliferating cells in uninjured mice and following kainic acid-induced seizures, I show that Cx36 deletion does not alter cell proliferation in the SGZ. However, the loss of Cx36 is neuroprotective following hippocampal injury without affecting neuroregenerative capacity. Finally, I demonstrate that the gap junction-like protein, pannexin2 (Panx2), is also expressed within mature neurons of the central nervous system (CNS) although functional channel activity and a role in neurogenesis have not elucidated. Here, I characterized the localization and morphology of Panx2 within hippocampal derived neurospheres in vitro and discovered that Panx2 exhibits a unique rod-like morphology with Type I and Type IIa NPCs. Together, these data implicate Cx36 in regulating postnatal NPC fate in the postnatal hippocampus and suggest a distinctive, regulatory role for Panx2 in neurogenesis.
URL: http://hdl.handle.net/10393/28246
http://dx.doi.org/10.20381/ruor-12464
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010
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