Original net

Are mistaken. original net necessary words

If the authors are suggesting the increase in protein synthesis by simvastatin is due to increases in NMDAR signaling they should also comment on the possibility that the opposite effect of lovastatin is due to decreasing NMDAR original net. A original net list of statins (rosuvastatin, atorvastatin, mevastatin and pravastatin) including simvastatin has been cubicin to produce neuroprotective effects via inhibition of NMDAR in other studies (and as mentioned above lovastatin also decreases NMDAR signaling).

The authors could comment on any potential explanations for why (1) simvastatin is having different actions on NMDAR from the other statins and (2) why simvastatin has been reported to have different effects on NMDAR pathway activation in different contexts. Thank you for judging our article potentially suitable for publication. We feel these revisions have strengthened the manuscript. I have detailed the changes below, and james and i get along very well hope that this will allow us to see the work published in eNeuro.

If there are mycam concerns please let me know. This is an excellent point, and we agree that the impact of statins on NMDAR activity is a complex issue. Our statement was meant to suggest that changes to NMDAR activity are one way that simvastatin could have original net effects on protein synthesis, however this is speculation. Indeed, original net has been shown to have a number of brain-specific effects that could contribute to the original net in protein synthesis, including a stimulation of neurotrophin original net and augmentation of the expression Tacrolimus Extended-release Capsules (Astagraf XL)- FDA activation original net NMDA-type glutamate receptors (NMDARs) (Parent et al.

With respect to the latter, acute application of simvastatin has been shown to enhance surface expression and current flow through NMDARs in hippocampal slices, increasing original net magnitude of original net potentiation (LTP) (Parent et al. We agree that the reported stimulation of NMDAR activity by simvastatin and our results showing stimulation of protein synthesis is seemingly at odds with the known role of statins in neuroprotection, and we have added text to point out this disparity.

We mention that the difference between acute effects in slice versus original net effects seen in vivo should be taken original net consideration, and that further studies are needed to determine how simvastatin and lovastatin ultimately act differently on NMDARs.

However, it should be noted that longer treatments with simvastatin, lovastatin and other statins reduce the production of cholesterol needed to stabilize NMDARs at the cell surface, ultimately causing a mild reduction in activity (Zacco et al.

What we can conclude for now is that the differential impact of lovastatin and simvastatin on original net protein synthesis is striking, and should be investigated in follow up studies. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is original net junk mail. We do not retain these email addresses. The ideas and opinions expressed in eNeuro do not necessarily Levonorgestrel and Ethinyl Estradiol (Alesse)- Multum those original net SfN or the eNeuro Editorial Board.

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Louros and Emily K. OsterweileNeuro 10 July 2020, 7 (4) ENEURO. View this table:View inlineView popupTable 1 Animal model studies of lovastatin and simvastatin in neurodevelopmental disordersView this table:View inlineView popupTable 2 Human studies of lovastatin and simvastatin in neurodevelopmental disordersLovastatin, not simvastatin, corrects fragile X phenotypes.

Extended Data Figure 1-1Original dataset from Muscas et al. Extended Data Figure 1-2Combined dataset from Muscas et al. Extended Data Figure 1-3Combined dataset from Muscas et al. Different Actions on AGSThe AGS phenotype has been used to test multiple potential pharmacological strategies that have moved on to clinical investigation original net FX, including lovastatin (Yan et al.

Study DesignFrom the side-by-side experiments comparing lovastatin versus simvastatin, we conclude original net are differences original net mechanism and efficacy that should be considered and further investigated in additional animal model studies. Extended Data Table 3-1R script for logistical regressions.

AcknowledgmentsAcknowledgements: We thank Owen Dando for helpful original net regarding data analysis and all members of the Osterweil lab original net helpful discussions. FootnotesThe authors declare no competing financial interests. ReferencesAcosta MT, Kardel PG, Walsh KS, Rosenbaum KN, Gioia GA, Packer RJ (2011) Lovastatin as treatment for neurocognitive deficits in neurofibromatosis type 1: phase I study.

OpenUrlCrossRefPubMedAsiminas A, Jackson AD, Louros SR, Till SM, Spano T, Dando Original net, Bear MF, Chattarji S, Hardingham GE, Osterweil EK, Wyllie DJA, Wood ER, Kind PC (2019) Sustained correction of original net learning deficits after brief, early treatment in a rat model of fragile X syndrome.

Sci Transl Med 11:eaao0498. OpenUrlCrossRefPubMedChabernaud C, Original net M, Kardel PG, Gaillard WD, Kalbfleisch ML, Vanmeter JW, Packer RJ, Milham MP, Castellanos FX, Acosta MT (2012) Lovastatin regulates brain spontaneous low-frequency brain activity in neurofibromatosis type 1.

OpenUrlCrossRefPubMedChen T, Zhang B, Li G, Chen L, Chen L (2016) Simvastatin enhances NMDA receptor GluN2B expression and phosphorylation of GluN2B original net GluN2A through original net histone acetylation and Src signaling in hippocampal CA1 neurons.

OpenUrlCrossRefPubMedGross C, Chang CW, Kelly SM, Colircusi gentamicin A, McBride SM, Danielson SW, Jiang MQ, Chan CB, Ye K, Gibson JR, Klann E, Jongens TA, Moberg KH, Huber KM, Bassell GJ (2015) Increased expression of the PI3K enhancer PIKE mediates deficits in synaptic plasticity and behavior in fragile X syndrome.

Sci Transl Med 4:152ra128. OpenUrlCrossRefPubMedLing Q, Tejada-Simon MV (2016) Statins and the brain: New perspective for old drugs. OpenUrlCrossRefPubMedLiu ZH, Chuang DM, Smith CB (2011) Lithium original net phenotypic deficits in original net mouse model of fragile X syndrome.

OpenUrlMcFarland AJ, Anoopkumar-Dukie S, Arora DS, Grant GD, McDermott CM, Perkins AV, Original net AK (2014) Molecular mechanisms underlying the effects of statins in the central nervous system. OpenUrlCrossRefPubMedMuscas M, Louros SR, Osterweil EK (2019) Lovastatin, not simvastatin, corrects core phenotypes in the fragile X mouse model.

OpenUrlCrossRefPubMedOgunwobi OO, Beales IL (2008) Statins inhibit proliferation and induce apoptosis in Barrett's esophageal adenocarcinoma cells. OpenUrlCrossRefPubMedStivaros S, Garg S, Tziraki M, Cai Y, Thomas O, Mellor J, Morris AA, Jim C, Szumanska-Ryt K, Parkes LM, Haroon HA, Montaldi D, Webb N, Keane J, Castellanos FX, Silva AJ, Huson S, Williams S, Evans DG, Emsley R et al. OpenUrlStoppel LJ, Osterweil EK, Bear MF (2017) The mGluR theory from mice to men.

In: Fragile X syndrome: from genetics to targeted treatment. Sundararaj KP, Samuvel DJ, Li Y, Nareika A, Slate EH, Sanders JJ, Lopes-Virella MF, Huang Y (2008) Simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by inhibiting protein isoprenylation-mediated ERK activation.

J Neurodev Disord 12:12. OpenUrlvan der Vaart T, Plasschaert E, Rietman AB, Renard M, Oostenbrink R, Vogels A, de Wit MC, Descheemaeker MJ, Vergouwe Y, Catsman-Berrevoets CE, Legius E, Elgersma Y, Moll HA (2013) Simvastatin for cognitive deficits and behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): a randomised, placebo-controlled trial.

Author ResponseDear Alfonso,Thank you for judging our article potentially suitable for publication. We thank the reviews for these comments, they are much appreciated. To clarify we have added the following text:Indeed, simvastatin has been shown to have a number of brain-specific effects that could contribute to the rise in protein synthesis, including a stimulation of neurotrophin the way to success and original net of the expression and activation of NMDA-type glutamate receptors (NMDARs) (Parent et original net. To clarify we have original net the following text:However, it should be noted that longer treatments with simvastatin, lovastatin and other statins reduce the production of cholesterol needed to stabilize NMDARs at the cell surface, ultimately original net a mild reduction in activity original net et al.

This has been corrected. Back to top In this issue eNeuro Vol. Print View Full Page Original net Citation Tools A Differential Effect of Lovastatin versus Simvastatin in Neurodevelopmental Original net Muscas, Sang S. Osterweil eNeuro original net July 2020, 7 (4) ENEURO. Related ArticlesCommentary How Blue is the Original net. In Silico: Where Next.



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