Here's a recent review from a Mayo Clinic researcher, MD.
ncbi.nlm.nih.gov/pubmed/286...
The locus coeruleus (LC) contains norepinephrine (NE)-synthesizing
neurons that send diffuse projections throughout the central nervous
system. The LC-NE system has a major role in arousal, attention and
stress responses. In the brain, NE may also contribute to long-term
synaptic plasticity, pain modulation, motor control, energy homeostasis
and control of local blood flow. The LC is severely affected in
neurodegenerative disorders including Parkinson disease (PD).
Involvement of the noradrenergic neurons of the LC precedes that of
dopaminergic neurons of the substantia nigra pars compacta and has been
increasingly recognized as a potential major contributor to cognitive
manifestations in early PD, particularly impaired attention. Abnormal
noradrenergic signaling may also potentially contribute to motor
manifestations of the disease.This makes the LC-NE system a major
contributor to the pathobiology and potential target for therapy of PD.
Locus coeruleus.
Benarroch EE.
Cell Tissue Res 2017 Jul 7.
See also.
Norepinephrine: the next therapeutics frontier for Parkinson's disease.
ncbi.nlm.nih.gov/pubmed/232...
Neuroimaging of Parkinson’s Disease: Expanding views.
ncbi.nlm.nih.gov/pmc/articl...
"In PD, there is neurodegeneration of the locus coeruleus and decreased norepinephrine output."
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Jere's more on the LC in humans.
The coeruleus/subcoeruleus complex in idiopathic rapid eye movement
sleep behaviour disorder
Brain, Volume 139:4 April 2016, Pages 1180–1188, open access.
academic.oup.com/brain/arti...
Here, we studied the integrity of the locus coeruleus/subcoeruleus
complex with neuromelanin-sensitive imaging in 21 patients with
idiopathic rapid eye movement sleep behaviour disorder and compared
the results with those from 21 age- and gender-matched healthy
volunteers.
The patients more frequently had preclinical markers of
alpha-synucleinopathies, including constipation, olfactory deficits,
orthostatic hypotension, and subtle motor impairment. Using
neuromelanin-sensitive imaging, reduced signal intensity was
identified in the locus coeruleus/subcoeruleus complex of the
patients with idiopathic rapid eye movement sleep behaviour.
Neuromelanin-sensitive imaging provides an early marker of
non-dopaminergic alpha-synucleinopathy that can be detected on an
individual basis.
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An excerpt from Benarroch's 2017 review of the locus coeruleus was intended to be
presented in 2 images accompanying this post.
Disease-modifying Potential of Nortriptyline in Parkinson’s Disease.
Rapid Response Innovation Awards, 2014.
michaeljfox.org/foundation/...
Monoamine reuptake inhibitors in Parkinson's disease.
Parkinsons Dis
2015;2015:609428.
ncbi.nlm.nih.gov/pmc/articl...
The serotonergic [4, 10–14] and noradrenergic [4, 10, 15] systems
also undergo degeneration in PD, leading to decreased levels of
serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline in both
striatal and extrastriatal structures.
Thus, in PD, degenerative changes extend beyond the dopaminergic
system and the interactions described between the dopaminergic,
serotonergic, and noradrenergic systems are perturbed. Currently,
dopamine replacement therapy with L-3,4-dihydroxyphenylalanine in
combination with an aromatic L-amino acid decarboxylase (AADC)
inhibitor such as benserazide or carbidopa (henceforth referred to
as L-DOPA) is the mainstay of PD treatment [16, 17].
However, L-DOPA targets mainly the dopamine-related pathology of PD
and fails to address the decreases in both 5-HT and noradrenaline.
In addition, with increasing duration of L-DOPA therapy, a range of
motor and nonmotor complications, encompassing dyskinesia,
wearing-off, and psychiatric manifestations, develop [18, 19].
Norepinephrine transporter occupancy by nortriptyline in patients
with depression: a positron emission tomography study with
(S,S)-[¹⁸F]FMeNER-D₂.
Int J Neuropsychopharmacol 2014
Apr;17(4):553-60.
academic.oup.com/ijnp/artic...
An inflammatory biomarker as a differential predictor of outcome of
depression treatment with escitalopram and nortriptyline.
Am J
Psychiatry 2014 Dec 1;171(12):1278-86; cited by 32].
ncbi.nlm.nih.gov/pubmed/250...
RESULTS: CRP level at baseline differentially predicted treatment
outcome with the two antidepressants (CRP-drug interaction: β=3.27,
95% CI=1.65, 4.89). For patients with low levels of CRP (<1
mg/L), improvement on the MADRS score was 3 points higher with
escitalopram than with nortriptyline. For patients with higher CRP
levels, improvement on the MADRS score was 3 points higher with
nortriptyline than with escitalopram. CRP and its interaction with
medication explained more than 10% of individual-level variance in
treatment outcome.
CONCLUSIONS: An easily accessible peripheral blood biomarker may
contribute to improvement in outcomes of major depressive disorder
by personalizing treatment choice.
A controlled trial of antidepressants in patients with Parkinson disease and depression.
Neurology 2009 Mar 10;72(10):886-92.
ncbi.nlm.nih.gov/pmc/articl...
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