Locus coeruleus and PD : Mayo review

[aspergerian]

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."

[aspergerian]

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.

[aspergerian]

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...