Abstract
Parkinson's disease (PD) is characterized by the degeneration of dopamine (DA) neurons in the substantia nigra pars compacta, and motor symptoms including bradykinesia, rigidity, and tremor at rest. These symptoms are exhibited when striatal dopamine concentration has decreased by around 70%. In addition to motor deficits, PD is also characterized by the non-motor symptoms. However, depletion of DA alone in animal models has failed to simultaneously elicit both the motor and non-motor deficits of PD, possibly because the disease is a multi-system disorder that features a profound loss in other neurotransmitter systems. There is growing evidence that additional loss of noradrenaline (NA) neurons of the locus coeruleus, the principal source of NA in the brain, could be involved in the clinical expression of motor as well as in non-motor deficits. In the present review, we analyze the latest evidence for the implication of NA in the pathophysiology of PD obtained from animal models of parkinsonism and from parkinsonian patients. Recent studies have shown that NA depletion alone, or combined with DA depletion, results in motor as well as in non-motor dysfunctions. In addition, by using selective agonists and antagonists of noradrenaline alpha receptors we, and others, have shown that α2 receptors are implicated in the control of motor activity and that α2 receptor antagonists can improve PD motor symptoms as well as l-Dopa-induced dyskinesia. In this review we argue that the loss of NA neurons in PD has an impact on all PD symptoms and that the addition of NAergic agents to dopaminergic medication could be beneficial in the treatment of the disease.
Highlights
Parkinson’s disease (PD) is a degenerative disorder of the central nervous system that impairs motor skills, cognitive processes, and other functions
It is well-known to be characterized by a progressive degeneration of dopaminergic (DAergic) neurons (70–75%) in the substantia nigra pars compacta (SNc), which results in a dopamine (DA) depletion in the striatum (Ehringer and Hornykiewicz, 1960)
Concomitant to the data obtained in non-human primates and genetic mice models of PD (Pifl et al, 1991; Rommelfanger and Weinshenker, 2007), we have recently found that NA depletion alone induces severe motor deficits similar to those reported after 6-OHDA lesion (Delaville et al, 2010)
Summary
Edited by: Elizabeth Abercrombie, RutgersNewark: The State University of New Jersey, USA. In addition to motor deficits, PD is characterized by the non-motor symptoms. Depletion of DA alone in animal models has failed to simultaneously elicit both the motor and non-motor deficits of PD, possibly because the disease is a multi-system disorder that features a profound loss in other neurotransmitter systems. There is growing evidence that additional loss of noradrenaline (NA) neurons of the locus coeruleus, the principal source of NA in the brain, could be involved in the clinical expression of motor as well as in non-motor deficits. In this review we argue that the loss of NA neurons in PD has an impact on all PD symptoms and that the addition of NAergic agents to dopaminergic medication could be beneficial in the treatment of the disease
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
