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CaMKII Metaplasticity Drives Aβ Oligomer-Mediated Synaptotoxicity
Patricio Opazo, Silvia Viana da Silva, Mario Carta, Christelle Breillat, Steven J Coultrap, Dolors Grillo-Bosch, Matthieu Sainlos, Françoise Coussen et al.. Cell reports, 2018-06-12
Topic: Disease mechanisms in lab and animal studies
Alzheimer's disease (AD) is emerging as a synaptopathology driven by metaplasticity. Indeed, reminiscent of metaplasticity, oligomeric forms of the amyloid-β peptide (oAβ) prevent induction of long-term potentiation (LTP) via the prior activation of GluN2B-containing NMDA receptors (NMDARs). However, the downstream Ca2+-dependent signaling molecules that mediate aberrant metaplasticity are unknown. In this study, we show that oAβ promotes the activation of Ca2+/calmodulin-dependent kinase II (CaMKII) via GluN2B-containing NMDARs. Importantly, we find that CaMKII inhibition rescues both the LTP impairment and the dendritic spine loss mediated by oAβ. Mechanistically resembling metaplasticity, oAβ prevents subsequent rounds of plasticity from inducing CaMKII T286 autophosphorylation, as well as the associated anchoring and accumulation of synaptic AMPA receptors (AMPARs). Finally, prolonged oAβ treatment-induced CaMKII misactivation leads to dendritic spine loss via the destabilization of surface AMPARs. Thus, our study demonstrates that oAβ engages synaptic metaplasticity via aberrant CaMKII activation.
Key findings
- In this study, we show that oAβ promotes the activation of Ca2+/calmodulin-dependent kinase II (CaMKII) via GluN2B-containing NMDARs.
- Importantly, we find that CaMKII inhibition rescues both the LTP impairment and the dendritic spine loss mediated by oAβ.
- Mechanistically resembling metaplasticity, oAβ prevents subsequent rounds of plasticity from inducing CaMKII T286 autophosphorylation, as well as the associated anchoring and accumulation of synaptic AMPA receptors (AMPARs).
- Finally, prolonged oAβ treatment-induced CaMKII misactivation leads to dendritic spine loss via the destabilization of surface AMPARs.
- Thus, our study demonstrates that oAβ engages synaptic metaplasticity via aberrant CaMKII activation.
Study details
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 22 of the 56 points we could judge it on, which is 39 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell reports) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29898386) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 22 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 22 of the 56 points we could judge it on is 39 out of 100. |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Opazo, P., da Silva, S. V., Carta, M., Breillat, C., Coultrap, S. J., Grillo-Bosch, D., et al. (2018). CaMKII Metaplasticity Drives Aβ Oligomer-Mediated Synaptotoxicity. Cell reports. https://doi.org/10.1016/j.celrep.2018.05.036
Vancouver
Opazo P, da Silva SV, Carta M, Breillat C, Coultrap SJ, Grillo-Bosch D, et al. CaMKII Metaplasticity Drives Aβ Oligomer-Mediated Synaptotoxicity. Cell reports. 2018. doi:10.1016/j.celrep.2018.05.036. PMID: 29898386.
BibTeX
@article{opazo2018-29898386,
author = {Opazo, Patricio and da Silva, Silvia Viana and Carta, Mario and Breillat, Christelle and Coultrap, Steven J and Grillo-Bosch, Dolors and Sainlos, Matthieu and Coussen, Françoise and others},
title = {{CaMKII Metaplasticity Drives Aβ Oligomer-Mediated Synaptotoxicity}},
journal = {Cell reports},
year = {2018},
doi = {10.1016/j.celrep.2018.05.036},
pmid = {29898386},
url = {https://doi.org/10.1016/j.celrep.2018.05.036}
}
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