Jeannotte AM, McCarthy JG, Sidhu A
Desipramine Induced Changes In The Norepineprhine Transporter, alpha- And beta- Synuclein In The Hippocampus, Amygdala And Striatum. [JOURNAL ARTICLE]
Neurosci Lett 2009 Oct 7.
The high incidence of depression in Parkinson's Disease (PD) has been well-documented in the clinic; however, the underlying molecular mechanisms of these overlapping pathologies remain elusive. Using a rodent model of depression, the Wistar-Kyoto (WKY) rat, we previously demonstrated that in the frontal cortex the altered expression and protein interactions of alpha- and gamma-synculein (alpha-Syn, gamma-Syn) were associated with dysregulated trafficking of the norepinephrine transporter (NET). Chronic treatment with Desipramine (DMI), a NET-selective antidepressant, caused a disappearance of depressive-like behavior that was accompanied by a change in alpha-Syn and gamma-Syn expression and their trafficking of NET. Using this same model, we examined the expression of NET, alpha-Syn and gamma-Syn in the hippocampus, amygdale, brainstem, and striatum, all regions implicated in the development or maintenance of depression or PD pathology. Following chronic treatment with DMI, we observed a significant decrease in NET in the hippocampus, amygdala, and brainstem; decrease in gamma-Syn in the hippocampus and amygdala; and, increase in alpha-Syn in the hippocampus and amygdala. Unexpectedly, we observed a significant decrease in alpha-Syn expression in the striatum of the WKY following chronic DMI treatment. The altered expression of NET, alpha-Syn and gamma-Syn in different brain suggest that DMI's ability to improve depressive-like behavior in a rodent is associated with region-specific changes in the regulation of NET by alpha- and gamma-Syn.
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