Differential response of the central noradrenergic nervous system to the loss of locus coeruleus neurons in Parkinson's disease and Alzheimer's disease

Brain Res. 2011 Feb 10;1373:240-52. doi: 10.1016/j.brainres.2010.12.015. Epub 2010 Dec 11.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / pathology*
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • Cell Count / methods
  • Dopamine beta-Hydroxylase / genetics
  • Dopamine beta-Hydroxylase / metabolism
  • Female
  • Fluoxetine / analogs & derivatives
  • Fluoxetine / pharmacokinetics
  • Humans
  • Locus Coeruleus / pathology*
  • Male
  • Middle Aged
  • Neurons / physiology*
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism
  • Parkinson Disease / pathology*
  • Protein Binding / drug effects
  • RNA, Messenger / metabolism
  • Tritium / pharmacokinetics
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism


  • Norepinephrine Plasma Membrane Transport Proteins
  • RNA, Messenger
  • Fluoxetine
  • Tritium
  • nisoxetine
  • Tyrosine 3-Monooxygenase
  • Dopamine beta-Hydroxylase