title: Differential response of the central noradrenergic nervous system to the loss of locus coeruleus neurons in Parkinson's disease and Alzheimer's disease.
abstract: In Parkinson's disease (PD), there is a significant loss of noradrenergic neurons in the locus coeruleus (LC) in addition to the loss of dopaminergic neurons in the substantia nigra (SN). The goal of this study was to determine if the surviving LC noradrenergic neurons in PD demonstrate compensatory changes in response to the neuronal loss, as observed in Alzheimer's disease (AD). Tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) mRNA expression in postmortem LC tissue of control and age-matched PD subjects demonstrated a significant reduction in the number of noradrenergic neurons in the LC of PD subjects. TH mRNA expression/neuron did not differ between control and PD subjects, but DBH mRNA expression/neuron was significantly elevated in PD subjects compared to control. This increase in DBH mRNA expression in PD subjects is not a response to neuronal loss because the amount of DBH mRNA expression/neuron in AD subjects was not significantly different from control. Norepinephrine transporter (NET) binding site concentration in the LC of PD subjects was significantly reduced over the cell body region as well as the peri-LC dendritic zone. In PD subjects, the loss of dendrites from surviving noradrenergic neurons was also apparent with TH-immunoreactivity (IR). This loss of LC dendritic innervation in PD subjects as measured by TH-IR was not due to LC neuronal loss because TH-IR in AD subjects was robust, despite a similar loss of LC neurons. These data suggest that there is a differential response of the noradrenergic nervous system in PD compared to AD in response to the loss of LC neurons.
authors.affiliation: Northwest Network for Mental Illness, Veterans Administration Puget Sound Health Care System, Seattle, Washington 98108, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: McMillan
authors.forename: Sylvia S
authors.initials: SS
authors.lastname: White
authors.forename: Allyn
authors.initials: A
authors.lastname: Franklin
authors.forename: J Lynne
authors.initials: JL
authors.lastname: Greenup
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: Murray A
authors.initials: MA
authors.lastname: Raskind
authors.forename: Patricia
authors.initials: P
authors.lastname: Szot
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002452:Cell Count / Q000379:methods; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D008125:Locus Coeruleus / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000502:physiology*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D010300:Parkinson Disease / Q000473:pathology*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D014316:Tritium / Q000493:pharmacokinetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D005473:Fluoxetine; D014316:Tritium; C011386:nisoxetine; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase