| Title |
Loss of Brain Norepinephrine Elicits Neuroinflammation-Mediated Oxidative Injury and Selective Caudo-Rostral Neurodegeneration
|
|---|---|
| Published in |
Molecular Neurobiology, July 2018
|
| DOI | 10.1007/s12035-018-1235-1 |
| Pubmed ID | |
| Authors |
Sheng Song, Lulu Jiang, Esteban A. Oyarzabal, Belinda Wilson, Zibo Li, Yen-Yu Ian Shih, Qingshan Wang, Jau-Shyong Hong |
| Abstract |
Environmental toxicant exposure has been strongly implicated in the pathogenesis of Parkinson's disease (PD). Clinical manifestations of non-motor and motor symptoms in PD stem from decades of progressive neurodegeneration selectively afflicting discrete neuronal populations along a caudo-rostral axis. However, recapitulating this spatiotemporal neurodegenerative pattern in rodents has been unsuccessful. The purpose of this study was to generate such animal PD models and delineate mechanism underlying the ascending neurodegeneration. Neuroinflammation, oxidative stress, and neuronal death in mice brains were measured at different times following a single systemic injection of lipopolysaccharide (LPS). We demonstrate that LPS produced an ascending neurodegeneration that temporally afflicted neurons initially in the locus coeruleus (LC), followed by substantia nigra, and lastly the primary motor cortex and hippocampus. To test the hypothesis that LPS-elicited early loss of noradrenergic LC neurons may underlie this ascending pattern, we used a neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to deplete brain norepinephrine. DSP-4 injection resulted in a time-dependent ascending degenerative pattern similar to that generated by the LPS model. Mechanistic studies revealed that increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (NOX2)-dependent superoxide/reactive oxygen species (ROS) production plays a key role in both LPS- and DSP-4-elicited neurotoxicity. We found that toxin-elicited chronic neuroinflammation, oxidative neuronal injuries, and neurodegeneration were greatly suppressed in mice deficient in NOX2 gene or treated with NOX2-specific inhibitor. Our studies document the first rodent PD model recapturing the ascending neurodegenerative pattern of PD patients and provide convincing evidence that the loss of brain norepinephrine is critical in initiating and maintaining chronic neuroinflammation and the discrete neurodegeneration in PD. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 17% |
| India | 1 | 17% |
| Australia | 1 | 17% |
| Switzerland | 1 | 17% |
| Unknown | 2 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 50% |
| Scientists | 3 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 38 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 6 | 16% |
| Researcher | 6 | 16% |
| Student > Ph. D. Student | 6 | 16% |
| Student > Master | 4 | 11% |
| Student > Doctoral Student | 3 | 8% |
| Other | 2 | 5% |
| Unknown | 11 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 13 | 34% |
| Medicine and Dentistry | 3 | 8% |
| Agricultural and Biological Sciences | 3 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
| Biochemistry, Genetics and Molecular Biology | 1 | 3% |
| Other | 3 | 8% |
| Unknown | 13 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 February 2022.
All research outputs
#7,579,758
of 23,114,117 outputs
Outputs from Molecular Neurobiology
#1,375
of 3,498 outputs
Outputs of similar age
#129,733
of 330,350 outputs
Outputs of similar age from Molecular Neurobiology
#55
of 135 outputs
Altmetric has tracked 23,114,117 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,498 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has gotten more attention than average, scoring higher than 54% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 330,350 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.
We're also able to compare this research output to 135 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.