Cortical serotonin and norepinephrine denervation in parkinsonism: preferential loss of the beaded serotonin innervation |
| |
Authors: | Tultul Nayyar Michael Bubser Marcus C. Ferguson M. Diana Neely J. Shawn Goodwin Thomas J. Montine Ariel Y. Deutch Twum A. Ansah |
| |
Affiliation: | Department of Neurobiology and Neurotoxicology, Meharry Medical College, 1005 D B Todd Blvd, Nashville, TN 37208, USA; Departments of Psychiatry and Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA |
| |
Abstract: | Parkinson's Disease (PD) is marked by prominent motor symptoms that reflect striatal dopamine insufficiency. However, non-motor symptoms, including depression, are common in PD. It has been suggested that these changes reflect pathological involvement of non-dopaminergic systems. We examined regional changes in serotonin (5-HT) and norepinephrine (NE) systems in mice treated with two different 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment paradigms, at survival times of 3 or 16 weeks after the last MPTP injection. MPTP caused a decrease in striatal dopamine concentration, the magnitude of which depended on the treatment regimen and survival interval after MPTP treatment. There was significant involvement of other subcortical areas receiving a dopamine innervation, but no consistent changes in 5-HT or NE levels in subcortical sites. In contrast, we observed an enduring decrease in 5-HT and NE concentrations in both the somatosensory cortex and medial prefrontal cortex (PFC). Immunohistochemical studies also revealed a decrease in the density of PFC NE and 5-HT axons. The decrease in the cortical serotonergic innervation preferentially involved the thick beaded but not smooth fine 5-HT axons. Similar changes in the 5-HT innervation of post-mortem samples of the PFC from idiopathic PD cases were seen. Our findings point to a major loss of the 5-HT and NE innervations of the cortex in MPTP-induced parkinsonism, and suggest that loss of the beaded cortical 5-HT innervation is associated with a predisposition to the development of depression in PD. |
| |
Keywords: | depression dopamine norepinephrine transporter prefrontal cortex serotonin transporter |
|
|