Cortical serotonin and norepinephrine denervation in parkinsonism: preferential loss of the beaded serotonin innervation.
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.
Nayyar
Tultul
T
Department of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37208, USA.
Bubser
Michael
M
Ferguson
Marcus C
MC
Neely
M Diana
MD
Shawn Goodwin
J
J
Montine
Thomas J
TJ
Deutch
Ariel Y
AY
Ansah
Twum A
TA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003714:Denervation / Q000379:methods; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology; D012701:Serotonin / Q000378:metabolism*
C040846:4-phenyl-1,2,3,6-tetrahydropyridine; D012701:Serotonin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D009638:Norepinephrine