Bipolar Disorder (BD) is a debilitating mental illness that presents as mood alterations between manic and depressive states. There remain large gaps in the knowledge surrounding the disease, due to three main issues in understanding the illness. First is a lack of an appropriate animal model that mimics both manic and depressive symptoms. Second is a lack of knowledge on the biological cause of the disease. Finally, a lack of knowledge on the precise mechanism of action of lithium (Li), the main treatment for BD prevents more progressive research into the disease.
Inflammation and a subsequent disruption of the blood-brain barrier (BBB) have recently been demonstrated in other psychiatric conditions, such as Alzheimer’s Disease (AD) and Schizophrenia (SZ). This mechanism remains to be fully investigated in BD. This thesis presents an inflammatory model of BBB disruption in rodents.
A study examining gene expression in discordant sibling pairs with SZ or BD discovered that the Max gene was elevated two-fold in bipolar patients as compared to their non-BD siblings. We aim to elucidate on these findings and examine the effect of common BD treatments on Max gene expression.
The first study utilized lipopolysaccharides (LPS) to induce an inflammatory response in the BBB, and sodium fluoroscein (NaF) to measure the levels of resulting disruption. It was shown that Li is unable to attenuate disruption of the BBB, and an LPS administration with Li pretreatment causes higher disruption than either substance alone in several brain regions.
The second study examined Max gene expression levels in naïve rats as a result of Li or valproate (VPA) treatment. VPA was shown to significantly downregulate the expression of Max in a rodent model.
These studies may provide insight into understanding the pathophysiology of BD, leading to better, more accurate animal models and more targeted therapies for the disorder. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22186 |
| Date | January 2017 |
| Creators | Sharma, Roohie |
| Contributors | Mishra, Ram, Neuroscience |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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