ScienceofParkinsons, locus coeruleus, and norepinephrine

[aspergerian]

Although essays in ScienceOfParkinsons.com are informative, they

merit scrutiny. Yes, atypicalities of alpha-synuclein and

pathologies in dopaminergic processes are important, as are

dopamine-related treatments. However, focusing entirely upon

dopamine seems to be an error of omission. Pathology in the locus

coeruleus and in noradrenergic processes not only are important but

may precede and (in many cases) initiate subsequent pathology in the

substantia nigra and in brain locales affected in dementia. The

locus coeruleus, noradrenergic, and norepinephrine do not appear in

the latest ScienceOfParkinsons essay.

scienceofparkinsons.com/201...

For instance, consider two recent cites.

Targeting the norepinephrinergic system in Parkinson's disease and

related disorders: The locus coeruleus story.

ncbi.nlm.nih.gov/pubmed/278...

In this regard, recent evidence suggests that LP in the locus

coeruleus (LC), the brain's main source of norepinephrine (NE),

precedes that of the SN, and, may be one of the very first

etiological events in PD. Interestingly, oxidized NE has

neuroprotective properties and may even prevent the formation of

toxic and higher molecular weight α-synuclein oligomers associated

with PD. Moreover, norepinephrinergic neurons directly innervate the

SN, and, LC lesioning causes more severe dopaminergic cell loss and

supplementary motor manifestations, as shown in preclinical

research. In fact, the LC may be considered one of the main

orchestrators that controls the other major monoaminergic nuclei,

such as the SN and raphe nuclei. Apart from its regulating function,

disruption of such a sustainable but vulnerable LC-NE system has

been linked to the cognitive pathophysiology of dementia as well.

Consequently, LC neuronal loss and the accompanying

norepinephrinergic deficiency constitute an important

pharmacological target for the (symptomatic) treatment of

PD/DLB/PDD. This review, therefore, summarizes and discusses all

relevant neurochemical research, including the intriguing link with

(prodromal) dementia....

The underlying mechanism of prodromal PD: insights from the

parasympathetic nervous system and the olfactory system.

ncbi.nlm.nih.gov/pubmed/282...

Even though not emphasized in this review, the sympathetic nervous

system may deserve more attention in attempting to understand

mechanisms of prodromal PD, as there is evidences for pre-motor

involvement of peripheral noradrenergic depletion [109], while the

noradrenergic nucleus locus coeruleus may be affected prior to the

substantia nigra in the prodromal stage.

Importantly, a search for coeruleus in SciOfPD retrieves only 1

essay (today, 2017-08-19)..

scienceofparkinsons.com/?s=...

IMO, ScienceOfParkinsons would be more scientific if

PD/DLB/PDD-findings related to the locus coeruleus and to

norepinephrine were included in at least some of the SOPD essays.

[aspergerian]

Here's another reference.

Norepinephrine: The redheaded stepchild of Parkinson's disease.

ncbi.nlm.nih.gov/pubmed/174...

PD is a true multisystem disorder marked by a profound but less

appreciated loss of cells in the locus coeruleus (LC), which contains

the major group of noradrenergic neurons in the brain. Historic and more

recent experiments exploring the role of norepinephrine (NE) in PD will

be analyzed in this review. First, we examine the evidence that NE is

neuroprotective and that LC degeneration sensitizes DA neurons to

damage. The second part of this review focuses on the potential

contribution of NE loss to the behavioral symptoms associated with PD.

We propose that LC loss represents a crucial turning point in PD

progression and that pharmacotherapies aimed at restoring NE have

important therapeutic potential.

[aspergerian in reply to aspergerian]

Another.

Noradrenergic

Modulation of Cognition in Health and Disease.

ncbi.nlm.nih.gov/pmc/articl...

According to Braak staging [120], LC accumulates α-synuclein and

degenerates prior to substantia nigra, which exacerbates

degeneration of the nigrostriatal pathway due to loss of

neuroprotective and trophic influences of NE [100].

[Hikoi]

"The locus coeruleus, noradrenergic, and norepinephrine do not appear in the latest ScienceOfParkinsons essay. "

While I agree pd is a multi systems condition i would not criticise the latest science of parkinsons blog site for not dicussing this in its latest entry. The purpose of this essay as stated at the beginning was to review the latest refinements and recommendations of the Dementia with Lewy Bodies Consortium, regarding the clinical and pathologic diagnosis of DLB.

I looked through the Consortium paper the essay was about, and didnt find particular reference to the "The locus coeruleus, noradrenergic, and norepinephrine." So To add this in to the essay would have muddied the water i think.

I admit i got a bit lost in your post here with the technical terms and that is why the science of parkinsons (sop) blog exists. - It aims to report science in plain language. I think it does a great job.

That being said it would be interesting to read more on your topic, i must check your links. I havent fully searched sop but i noted there is a blog on the site asking for feedback / improvements.

scienceofparkinsons.com/201...

[aspergerian in reply to Hikoi]

I think I searched the entire so site and found only the one LC reference.

[aspergerian]

Here is an excerpt from:

ncbi.nlm.nih.gov/pubmed/278...

...the relative success of DA replacement strategies solely targeting

the motor impairment further emphasizes the contemporary lack of

validated treatments for the spectrum of non-motor problems specified

above. In this respect, the marked reduction of NE throughout PD brain

remains largely neglected in much of current research, notwithstanding

firm evidence that LP in the LC occurs much earlier and even to greater

extent than in the SN (Del Tredici et al., 2002; German et al., 1992;

Rommelfanger and Weinshenker, 2007).

Furthermore, LC neuronal loss may be one of the primary pathological

events of PD etiology, since norepinephrinergic neurons directly

innervate the SN, facilitating burst firing, and, additional LC

lesioning causes even more severe dopaminergic cell loss and

supplementary motor manifestations, as shown in PD animal models

(Benarroch, 2009).

In fact, NE has profound effects on brain inflammation, oxidative stress

(O'Donnell et al., 2012), and possesses neuroprotective properties that

may even delay dementia onset as hypothesized by Rommelfanger and

Weinshenker (2007).

.

[aspergerian]

The first two paragraphs in an article's introduction merit attention.

The importance of dopamine in PD motor symptoms ought not preclude

research into other neurotransmitters affected in PD.

Monoamine Reuptake Inhibitors in Parkinson's Disease.

ncbi.nlm.nih.gov/pmc/articl...