Abstract
Noradrenergic neurons in the locus coeruleus (LC) are significantly reduced in Parkinson’s disease (PD) and the LC exhibits neuropathological changes early in the disease process. It has been suggested that a loss of LC neurons can enhance the susceptibility of dopaminergic neurons to damage. To determine if LC noradrenergic innervation protects dopaminergic neurons from damage, the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was administered to adult male C57Bl/6 mice 3 days after bilateral LC administration of 6-hydroxydopamine (6OHDA), a time when there is a significant reduction in LC neuronal number and innervation to forebrain regions. To assess if LC loss can affect dopaminergic loss four groups of animals were studied: control, 6OHDA, MPTP, and 6OHDA + MPTP; animals sacrificed 3 weeks after MPTP administration. The number of dopaminergic neurons in the substantia nigra (SN) and ventral tegmental area (VTA), and noradrenergic neurons in the LC were determined. Catecholamine levels in striatum were measured by high-pressure liquid chromatography. The loss of LC neurons did not affect the number of dopaminergic neurons in the SN and VTA compared to control; however, LC 6OHDA significantly reduced striatal dopamine (DA; 29% reduced) but not norepinephrine (NE) concentration. MPTP significantly reduced SN and VTA neuronal number and DA concentration in the striatum compared to control; however, there was not a correlation of striatal DA concentration with SN or VTA neuronal number. Administration of 6OHDA prior to MPTP did not enhance MPTP-induced damage despite an effect of LC loss on striatal DA concentration. However, the loss of LC neurons before MPTP resulted now in a correlation between SN and VTA neuronal number to striatal DA concentration. These results demonstrate that the loss of either LC or DA neurons can affect the function of each others systems, indicating the importance of both the noradrenergic and dopaminergic system in PD.
Highlights
Parkinson’s disease (PD) is a neurological disorder that is characterized by various motor deficits including tremor, rigidity, and bradykinesia (Singh et al, 2007)
SUMMARY The loss of Locus coeruleus (LC) neurons and forebrain innervation prior to the administration of MPTP does not result in an enhanced loss of dopaminergic neurons in the substantia nigra (SN) and ventral tegmental area (VTA) or DA concentration in the striatum
When 6OHDA and MPTP are sequentially administered to animals a correlation exists between SN and VTA neuronal number with striatal DA
Summary
Parkinson’s disease (PD) is a neurological disorder that is characterized by various motor deficits including tremor, rigidity, and bradykinesia (Singh et al, 2007). The cause of these motor symptoms is the loss of dopaminergic neurons in the substantia nigra (SN) pars compacta and subsequently reduced dopamine (DA) concentration in the striatum (Gibb, 1991; Gibb and Lees, 1991; Damier et al, 1999). The midbrain dopaminergic neurons in the SN and ventral tegmental area (VTA) receive direct innervation from LC noradrenergic neurons (Swanson and Hartman, 1975; Jones and Moore, 1977; Phillipson, 1979; Simon et al, 1979; Jones and Yang, 1985; Fritschy and Grzanna, 1990; Szot et al, 2012). A reduction in LC noradrenergic activity results in reduced activity of SN and VTA neurons (Grenhoff and Svensson, 1989, 1993; Grenhoff et al, 1993, 1995; Guiard et al, 2008; Wang et al, 2010) and dopamine-induced behavior (Antelman and Caggiula, 1977; Chopin et al, 1999; Rommelfanger et al, 2007; Grimbergen et al, 2009; Taylor et al, 2009; Wang et al, 2010)
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.
