| Title |
Indomethacin promotes survival of new neurons in the adult murine hippocampus accompanied by anti-inflammatory effects following MPTP-induced dopamine depletion
|
|---|---|
| Published in |
Journal of Neuroinflammation, May 2018
|
| DOI | 10.1186/s12974-018-1179-4 |
| Pubmed ID | |
| Authors |
Elisabeth G. Hain, Maria Sparenberg, Justyna Rasińska, Charlotte Klein, Levent Akyüz, Barbara Steiner |
| Abstract |
Parkinson's disease (PD) is characterized by dopaminergic cell loss and inflammation in the substantia nigra (SN) leading to motor deficits but also to hippocampus-associated non-motor symptoms such as spatial learning and memory deficits. The cognitive decline is correlated with impaired adult hippocampal neurogenesis resulting from dopamine deficit and inflammation, represented in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) mouse model of PD. In the inflammatory tissue, cyclooxygenase (COX) is upregulated leading to an ongoing inflammatory process such as prostaglandin-mediated increased cytokine levels. Therefore, inhibition of COX by indomethacin may prevent the inflammatory response and the impairment of adult hippocampal neurogenesis. Wildtype C57Bl/6 and transgenic Nestin-GFP mice were treated with MPTP followed by short-term or long-term indomethacin treatment. Then, aspects of inflammation and neurogenesis were evaluated by cell counts using immunofluorescence and immunohistochemical stainings in the SN and dentate gyrus (DG). Furthermore, hippocampal mRNA expression of neurogenesis-related genes of the Notch, Wnt, and sonic hedgehog signaling pathways and neurogenic factors were assessed, and protein levels of serum cytokines were measured. Indomethacin restored the reduction of the survival rate of new mature neurons and reduced the amount of amoeboid CD68+ cells in the DG after MPTP treatment. Indomethacin downregulated genes of the Wnt and Notch signaling pathways and increased neuroD6 expression. In the SN, indomethacin reduced the pro-inflammatory cellular response without reversing dopaminergic cell loss. Indomethacin has a pro-neurogenic and thereby restorative effect and an anti-inflammatory effect on the cellular level in the DG following MPTP treatment. Therefore, COX inhibitors such as indomethacin may represent a therapeutic option to restore adult neurogenesis in PD. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 49 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 14% |
| Student > Bachelor | 7 | 14% |
| Student > Master | 4 | 8% |
| Student > Doctoral Student | 3 | 6% |
| Lecturer | 3 | 6% |
| Other | 7 | 14% |
| Unknown | 18 | 37% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 12 | 24% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 6% |
| Biochemistry, Genetics and Molecular Biology | 3 | 6% |
| Nursing and Health Professions | 3 | 6% |
| Medicine and Dentistry | 3 | 6% |
| Other | 4 | 8% |
| Unknown | 21 | 43% |
Attention Score in Context
This research output has an Altmetric Attention Score of 11. 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 15 June 2018.
All research outputs
#3,168,495
of 23,577,654 outputs
Outputs from Journal of Neuroinflammation
#533
of 2,726 outputs
Outputs of similar age
#63,904
of 331,960 outputs
Outputs of similar age from Journal of Neuroinflammation
#15
of 78 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,726 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.7. This one has done well, scoring higher than 78% of its peers.
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We're also able to compare this research output to 78 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.