Related Experiment Video
Updated: Jun 19, 2026

A Plate-Based Assay for the Measurement of Endogenous Monoamine Release in Acute Brain Slices
Published on: August 11, 2021
Desipramine induced changes in the norepinephrine transporter, alpha- and gamma-synuclein in the hippocampus,
Alexis M Jeannotte1, John G McCarthy, Anita Sidhu
1Department of Biochemistry and Molecular and Cell Biology, Georgetown University Medical Center, Georgetown University, Washington, DC 20007, United States.
Abstract:
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.
Related Concept Videos
Drugs Affecting Neurotransmitter Release or Uptake
Drugs Affecting Neurotransmitter Synthesis
Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs
Antidepressant Drugs: MAOIs and Other Agents
Parkinson's Disease: Treatment
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of its...
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...

