| dc.contributor.author | Ward, Nicole Leanne. | en_US |
| dc.date.accessioned | 2014-10-21T12:35:49Z | |
| dc.date.available | 1999 | |
| dc.date.issued | 1999 | en_US |
| dc.identifier.other | AAINQ49297 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55680 | |
| dc.description | Nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4) are neurotrophins and bind to the p75 NGF receptor (p75NGFR). Previously our laboratory suggested that p75NGFR induced apoptosis in a subpopulation of cholinergic forebrain neurons during postnatal development. We attempted to identify in vivo (i) the putative p75NGFR "neurocidal", or death-inducing ligand that induced apoptotic cell death of these neurons; (ii) the intracellular signaling pathways activated by p75NGFR during developmental apoptotic cell death and following injury in cholinergic forebrain neurons; and (iii) the role of p75NGFR in the potential atrophy or maintenance of cholinergic medial septum neurons during aging. | en_US |
| dc.description | We determined that BDNF and NT-4 were not "neurocidal" in the developing cholinergic medial septum by analyzing transgenic mice lacking BDNF or NT-4. BDNF-deficient (--/--) mice had fewer and smaller ChAT-positive neurons, and ∼3 times more TUNEL-labeled cells in the medial septum compared to control littermates, and had reduced cholinergic hippocampal. innervation. | en_US |
| dc.description | p75NGFR can signal in vitro through activation of the c-Jun N-terminal kinase (JNK) pathway and nuclear translocation of NFKB. Activation of JNK can lead to apoptosis in some cells. We investigated these activities in cholinergic forebrain neurons of control and p75NGFR (--/--) mice during development and following fimbria fornix transection. | en_US |
| dc.description | We also investigated whether the absence of p75NGFR would affect the cholinergic septohippocampal system during aging in mice. In young, middle aged, and aged control mice, the total number and size of ChAT-positive medial septum neurons and the cholinergic hippocampal innervation did not differ. | en_US |
| dc.description | BDNF is necessary for normal postnatal maturation of cholinergic forebrain neurons, and p75NGFR does not signal via the JNK cascade, activation of NFKB, or induce apoptotic cell death in these neurons. Lastly, p75NGFR does not appear to have a critical role in maintaining the cholinergic cell number or size during senescence. (Abstract shortened by UMI.) | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 1999. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Biology, Neuroscience. | en_US |
| dc.title | Neurotrophins and neurotrophin signal transduction in cholinergic neurons of the mouse forebrain. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
