Graduate Program
Biological Sciences
Degree Name
Master of Science (MS)
Semester of Degree Completion
2006
Thesis Director
Britto Nathan
Thesis Committee Member
Gary Bulla
Thesis Committee Member
Charles Costa
Abstract
Apolipoprotein E (apoE), a lipid transporting protein, is a major risk factor for developing Alzheimer's disease (AD). Previous studies have shown that apoE is expressed at high concentrations in the olfactory nerve (ON) and around the glomeruli of the olfactory bulb (OB) and that the apoE levels in these regions increase substantially following lesioning of the source of the olfactory nerves, the olfactory epithelium (OE). However, the mechanism(s) underlying the contribution of apoE to neuronal functioning and developing AD are not clearly understood. To investigate and better clarify the role of apoE in nerve regeneration, I examined the presence and concentration of apoE in the olfactory epithelium (OE), the rate of cell proliferation in the OE, the rate of regeneration of the OE, the rate of maturation of neurons in the OE and the rate of synaptogenesis of neurons of the OE all in response to induced injury to the olfactory epithelium.
I evaluated the immunoreactivity of apoE in apoE wild type (WT) mice and aроЕ deficient mice (apoE knock-out (KO)). ApoE immunoreactivity was found only in the OE of WT mice. ApoE was localized to several cell types including ON, olfactory ensheathing glial (OEG), endothelial cells and Sustentecular (Sus) cells.
I predicted that apoE levels in the OE of WT mice, in response to injury of the OОЕ would increase as it does in the OB. To test this hypothesis, I induced injury to the OE of apoE WT mice and allowed them time to heal. Data revealed that apoE levels initially declined followed by an upregulation to above control levels in the second week postlesioning. ApoE levels dropped slightly after the seventh week back towards control levels.
It has been found that the CNS is capable of neurogenesis. Thus I examined the influence of apoE on the cell proliferation rate of the OE in response to induced injury to the OE. Cell proliferation in the OE of WT and KO mice was detected by BrdU, a DNA marker that detects cells undergoing mitosis. My results indicated no significant difference in cell proliferation rates for both strains of mice as the rate increased after the third day and peaked at the seventh followed by an abrupt decline to normal during the second week.
My next study involved determining whether apoE influenced the rate of maturation of ON in the regenerating OE. Using OMP, a marker for mature ON, 1 examined the OE of apoE WT and KO mice. The data suggests that there is no observed delay in the rate of ON maturation in the apoE KO mice.
Previous studies indicated that ON maturation is partly dependant on the ability of immature ON to form synapses in the target organs. ApoE has also been implicated in the development and functioning synapses. I postulated that ON in apoE WT mice would undergo synaptogenesis more efficiently than apoE KO mice. To test this hypothesis I used synaptophysin (SYN), a synaptic marker, to determine the rate of synaptogenesis between WT and KO mice. Synaptogenesis occurred in apoE KO mice at about 2 weeks slower than it did in WT mice.
These results demonstrate that the OE is able to undergo neuronal regeneration and maturation. However, the differential pattern of this phenomenon between apoE WT and KO mice over eight weeks after peripheral lesioning of the OE illustrates the profound effect apoE has on not only neuronal regeneration but plasticity as well.
Recommended Citation
Nwosu, Ikemefuna T., "The effects of ApoE on olfactory neuron plasticity in mice" (2006). Masters Theses. 739.
https://thekeep.eiu.edu/theses/739
