Desipramine induced changes in the norepinephrine transporter, alpha- and gamma-synuclein in the hippocampus, amygdala and striatum.
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-synuclein (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.
Jeannotte
Alexis M
AM
Department of Biochemistry and Molecular and Cell Biology, Georgetown University Medical Center, Georgetown University, Washington, DC 20007, United States.
McCarthy
John G
JG
Sidhu
Anita
A
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000096:biosynthesis*; D009928:Organ Specificity; D051381:Rats; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D051844:alpha-Synuclein / Q000096:biosynthesis*; D051846:beta-Synuclein / Q000096:biosynthesis*
D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D050484:Norepinephrine Plasma Membrane Transport Proteins; D051844:alpha-Synuclein; D051846:beta-Synuclein; D003891:Desipramine