Graduate Program

Biological Sciences

Degree Name

Master of Science (MS)

Semester of Degree Completion

2009

Thesis Director

Britto Nathan

Thesis Committee Member

Gary Bulla

Thesis Committee Member

Marina Marjanovic

Abstract

The purpose of this investigation was to investigate genetic and age~related differences in the mammalian olfactory system. The molecule of interest is apolipoprotein E (apoE), a component oflipoprotein molecules which functions in the transport of cell membrane components (triglycerides, lipids, and cholesterol). Specifically in the nervous system, apoE is synthesized by glial cells that function in recycling dead nervous tissue components for delivery to growing or dividing neurons. ApoE is present in three protein isofon11s: apoE2, which has been associated with type III hyperlipoproteinemia; apoE3, rhe normal human isoforrn; and apoE4, which has been associated with Alzheimer's disease (AD). The model of study utilized in the mouse olfactory system, composed of the olfactory epithelium and olfa.ctory bulb, which functions in smell recognition via olfactory receptor neurons (ORJ\!) which associated with odorant molecules present in the nasal cavity and transmit chemical infonnation to the brain for processmg. T_he 0'1~1 actorye p1• tl1 e_11·m n contam• s severa1_ m,. stm• ct neuronal• ce 1,1 t ypes: e1i1• v1·d m· g basal cells, immature ORN, and mature ORN. In the research undertaken, mice were divided into several treatment groups: wild-type young (WT Y), wild-type old (WT 0), apoE knockout young (KOY), and apoE knockout old (KO 0). Cell counts were made for each of the different neuronal cell types in the OE and differences in cell division rates and tissue growth was examined between each of the four treatment groups. Overall, WT Y compared to WT 0 resulted in a decrease in overall olfactory epithelium thickness for the older individuals, as well as a decrease in numbers of each of the specific neuron types quantified. This result was also found in KO Y con1pared to KO 0, with older a..'limals displaying significantly lower numbers of neurons compared to young individuals. WT Y compared to KO Y did shO\v a slight decrease in neuron counts in the apoE knockout, but was not statistically significant. Finally, a comparison between WT Y and KO Oto examine the combinatory effect of aging and absence of apoE showed the most significant difference in neuron types, with the older apoE knockout individuals showing a drastically lower overall olfactory epithelium thiclrness and for each of the neuron types. These conclusions demonstrate the affect of aging on neuron tissue regeneration and recycn'. ng mec1n aru• sms, b em• g a re du ct1• 011m' neuron ti•s sue growt1i :1a nd neurona1• ee1l1, d-1" v•1 s• 1on.T l. n e absence of apoE in younger individuals did not show significant reduction in neuron tissue growth to the same degree as in the older individuals, where neuron tissue growth was significantly delayed, suggesting apoE may play a much more vital role in older individuals. Finally, the combination of aging and absence of apoE der11onstratesa severe decrease in neuron tissue growth, suggesting an additive affect and supportive of the conclusion that apoE plays a more important role in neuron growth and repair mechanisms as an individual ages.

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