Loss of Norepinephrine Causes Parkinson-Like Tremor in Mice

Gary W. Miller, Ph.D.
Rollins School of Public Health, Emory University
U54ES012068

Parkinson’s disease is a chronic neurodegenerative disease that is characterized by the loss of dopamine producing neurons in the substantia nigra region of the brain. There is also a simultaneous loss of norepinephrine producing neurons in a region called the locus coeruleus. Administration of methyl phenyl tetrahydropyridine (MPTP) to laboratory animals is a common model for Parkinson’s disease; however MPTP does not cause the motor deficits seen in humans with Parkinson’s disease.

NIEHS-supported investigators at Emory University working with collaborators at the University of Georgia tested if the loss of norepinephrine neurons was necessary for the motor deficits seen in Parkinson’s disease. They used transgenic mice that totally lack norepinephrine altogether.

The researchers detected no motor deficits in control mice treated with MPTP despite an 80 percent reduction in the number of dopamine producing cells. On the other hand, the norepinephrine-lacking mice exhibited motor deficits in most tests along with other movement disorders despite having normal dopamine levels. The researchers were able to reverse the motor effects by supplementation with a norepinephrine precursor. Additional experiments demonstrated that increased levels of norepinephrine protected dopamine producing neurons from MPTP toxicity.

This study suggests that loss of locus coeruleus neurons contributes to the motor deficits seen in Parkinson’s disease. Along with adding new insights to the laboratory models used to recapitulate Parkinson’s symptoms, it implies that administration of norepinephrine-like drugs could have dual therapeutic effects by both preventing dopamine neuron loss and alleviating motor deficits associated with Parkinson’s disease.

Citation: Rommelfanger KS, Edwards GL, Freeman KG, Liles LC, Miller GW, Weinshenker D. Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice. Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13804-9.  [Abstract] (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17702867&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)