Cortical serotonin and norepinephrine denervation in parkinsonism: preferential loss of the beaded serotonin innervation.

Nayyar T, Bubser M, Ferguson MC, Neely MD, Shawn Goodwin J, Montine TJ, Deutch AY, Ansah TA
Eur J Neurosci. 2009 30 (2): 207-16

PMID: 19659923 · PMCID: PMC2765981 · DOI:10.1111/j.1460-9568.2009.06806.x

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.

MeSH Terms (16)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Aged Aged, 80 and over Animals Cell Count Cerebral Cortex Denervation Dopamine Humans Male Mice Mice, Inbred C57BL Middle Aged Norepinephrine Parkinsonian Disorders Serotonin

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