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The Effects of Opioid Receptor Disruption and Genetic Background on Cytogenesis in the Dentate Gyrus and Spinal Cord

by
Tara P. Cominski
M.S. in Biology
Seton Hall University - 2002



Thesis Advisor: John Pintar, Ph.D.
Graduate Program in Neuroscience

CABM, Room 010
Piscataway, NJ

Friday, September 10, 2010
10:00 a.m.


Abstract

The mechanisms underlying adult neurogenesis in the granule cell layer (GCL) of the dentate gyrus (DG) remain largely unknown. This endogenous stem cell population serves as a potential target for treatment of neurodegenerative diseases like Alzheimerís and Parkinsonís, therefore, it is important to understand how it is regulated and to identify factors that can influence it. Although studies suggest that the opioid system can affect cell proliferation and growth in the CNS, the role of the opioid system on adult neurogenesis in the DG has not been carefully examined. In the current study, cell proliferation, cell survival, and cell fate were measured in the DG of mu opioid receptor (MOR-1) knockout mice on two different genetic backgrounds. The data indicate that the total number of proliferating cells is significantly increased in MOR-1 KO mice compared to wild-type (WT) mice on both the C57BL/6 and the 129S6 strains. The survival rate of newly born cells is strain and genotype dependent, while cell fate remains unaffected. Survival rate is enhanced in C57BL/6 MOR-1 KOs compared to C57BL/6 WT mice and decreased in 129S6 MOR-1 KO mice compared to 129S6 WT mice. These data suggest that the opioid system is an important factor in the maintenance of adult neurogenesis in the DG.
The spinal cord is another region of the CNS that houses a proliferative cell population. In contrast to the DG, it is comprised of mostly glial precursors, thus, we wanted to determine if the spinal cord responds to opioid receptor disruption similarly to the DG. Therefore, cell proliferation, cell survival, and cell fate were examined in the spinal cord of opioid receptor knockout mice. The data indicate that baseline levels of cell proliferation are decreased in C57BL/6 opioid receptor knockout mice compared to C57BL/6 WT, but not in 129S6 opioid receptor knockout mice. Cell survival and cell fate in the spinal cord are not affected by opioid receptor disruption. Following a contusion spinal cord injury, opioid receptor knockout mice appear to have increased levels of cell proliferation for as many as 30 days following SCI as well as a lower amount of locomotor recovery, as measured by the BMS scale, when compared to 129S6 wild-type mice. This data suggests that the opioid system is important in the repair processes that occur following spinal cord injury.


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