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Permanent link (DOI): https://doi.org/10.7939/R3Q81502J
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The glutamate transporters' role in neuropathic pain and cognitive deficits in an animal model of multiple sclerosis Open Access
- Other title
- Type of item
- Degree grantor
University of Alberta
- Author or creator
Olechowski, Camille J
- Supervisor and department
Smith, Peter (Pharmacology)
Kerr, Bradley (Anesthesiology and Pain Medicine)
- Examining committee member and department
Pitman, Quentin (Physiology and Pharmacology)
Todd, Kathryn (Psychiatry)
Winship, Ian (Psychiatry)
Centre for Neuroscience
- Date accepted
- Graduation date
Doctor of Philosophy
- Degree level
Multiple Sclerosis (MS) is a chronic disease of the central nervous system characterized by demyelination, inflammation and axonal injury. Chronic pain and cognitive deficits affect a large percentage of MS patients. While a number of animal models are available to study the pathophysiology of MS, studies determining the profile of the above-mentioned symptoms associated with MS in these models are minimal. The purpose of this thesis was to characterize both behavioural and cellular changes in sensory and cognitive processes of the MOG35-55 EAE mouse model of MS.
In chapter 2, I characterized the changes in pain sensitivity that arises in a chronic relapsing model of EAE. I found that female C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG35-55) develop a robust allodynia to both cold and tactile stimuli
In chapter 3, work was undertaken to determine the underlying mechanisms that generate neuropathic pain in the MOG35-55 EAE model. Additionally, I was interested in how MOG35-55 EAE mice respond to a persistent noxious stimulus. Mice with EAE showed a significant decrease in elicited pain behaviours in response to subcutaneous injection of formalin. I demonstrated that these effects are mediated by decreased glutamate transporter expression associated with the disease.
My experiments in Chapter 4 addressed changes in cognitive ability across different severities of EAE to determine if altered pain sensitivity is also associated with behavioural signs indicative of cognitive impairment in this model. I also used the β-lactam antibiotic ceftriaxone, an agent know to increase glutamate transporter levels in vivo to determine if I could attenuate allodynia and NOR deficits by increasing glutamate transporter activity. Ceftriaxone prevented tactile hypersensitivity and normalized performance in the NOR assay in EAE mice
This work validates the use of the mouse MOG35-55 EAE model for studying sensory and cognitive changes in a laboratory setting. Furthermore, the results suggest that the glutamate transporter system may be in ideal target for treatment of these changes in patients suffering from similar sensory and cognitive deficits.
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- Citation for previous publication
Olechowski CJ, et al. (2013) Changes in nociceptive sensitivity and object recognition in experimental autoimmune encephalomyelitis (EAE). Exp. NeurologyOlechowski CJ, et al. (2010) A diminished response to formalin stimulation reveals a role for the glutamate transporters in the altered pain sensitivity of mice with experimental autoimmune encephalomyelitis (EAE). Pain 149(3):565-572.Olechowski CJ, Truong JJ, & Kerr BJ (2009) Neuropathic pain behaviours in a chronic-relapsing model of experimental autoimmune encephalomyelitis (EAE). Pain 141(1-2):156-164.
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