MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish

Research output: Contribution to journal › Journal article › Research › peer-review

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MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish. / Lundegaard, Pia R.; Anastasaki, Corina; Grant, Nicola J.; Sillito, Rowland R; Zich, Judith; Zeng, Zhiqiang; Paranthaman, Karthika; Larsen, Anders Peter; Armstrong, J. Douglas; Porteous, David J.; Patton, E. Elizabeth.

In: Chemistry & Biology, Vol. 22, No. 10, 22.10.2015, p. 1335-1346.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Lundegaard, PR, Anastasaki, C, Grant, NJ, Sillito, RR, Zich, J, Zeng, Z, Paranthaman, K, Larsen, AP, Armstrong, JD, Porteous, DJ & Patton, EE 2015, 'MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish', Chemistry & Biology, vol. 22, no. 10, pp. 1335-1346. https://doi.org/10.1016/j.chembiol.2015.08.010

APA

Lundegaard, P. R., Anastasaki, C., Grant, N. J., Sillito, R. R., Zich, J., Zeng, Z., Paranthaman, K., Larsen, A. P., Armstrong, J. D., Porteous, D. J., & Patton, E. E. (2015). MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish. Chemistry & Biology, 22(10), 1335-1346. https://doi.org/10.1016/j.chembiol.2015.08.010

Vancouver

Lundegaard PR, Anastasaki C, Grant NJ, Sillito RR, Zich J, Zeng Z et al. MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish. Chemistry & Biology. 2015 Oct 22;22(10):1335-1346. https://doi.org/10.1016/j.chembiol.2015.08.010

Author

Lundegaard, Pia R. ; Anastasaki, Corina ; Grant, Nicola J. ; Sillito, Rowland R ; Zich, Judith ; Zeng, Zhiqiang ; Paranthaman, Karthika ; Larsen, Anders Peter ; Armstrong, J. Douglas ; Porteous, David J. ; Patton, E. Elizabeth. / MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish. In: Chemistry & Biology. 2015 ; Vol. 22, No. 10. pp. 1335-1346.

Bibtex

@article{d2b85549eafe41aab667ec58ee8f459a,

title = "MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish",

abstract = "Altered phosphodiesterase (PDE)-cyclic AMP (cAMP) activity is frequently associated with anxiety disorders, but current therapies act by reducing neuronal excitability rather than targeting PDE-cAMP-mediated signaling pathways. Here, we report the novel repositioning of anti-cancer MEK inhibitors as anxiolytics in a zebrafish model of anxiety-like behaviors. PDE inhibitors or activators of adenylate cyclase cause behaviors consistent with anxiety in larvae and adult zebrafish. Small-molecule screening identifies MEK inhibitors as potent suppressors of cAMP anxiety behaviors in both larvae and adult zebrafish, while causing no anxiolytic behavioral effects on their own. The mechanism underlying cAMP-induced anxiety is via crosstalk to activation of the RAS-MAPK signaling pathway. We propose that targeting crosstalk signaling pathways can be an effective strategy for mental health disorders, and advance the repositioning of MEK inhibitors as behavior stabilizers in the context of increased cAMP.",

author = "Lundegaard, {Pia R.} and Corina Anastasaki and Grant, {Nicola J.} and Sillito, {Rowland R} and Judith Zich and Zhiqiang Zeng and Karthika Paranthaman and Larsen, {Anders Peter} and Armstrong, {J. Douglas} and Porteous, {David J.} and Patton, {E. Elizabeth}",

year = "2015",

month = oct,

day = "22",

doi = "10.1016/j.chembiol.2015.08.010",

language = "English",

volume = "22",

pages = "1335--1346",

journal = "Chemistry and Biology",

issn = "2451-9448",

publisher = "Elsevier",

number = "10",

}

RIS

TY - JOUR

T1 - MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish

AU - Lundegaard, Pia R.

AU - Anastasaki, Corina

AU - Grant, Nicola J.

AU - Sillito, Rowland R

AU - Zich, Judith

AU - Zeng, Zhiqiang

AU - Paranthaman, Karthika

AU - Larsen, Anders Peter

AU - Armstrong, J. Douglas

AU - Porteous, David J.

AU - Patton, E. Elizabeth

PY - 2015/10/22

Y1 - 2015/10/22

N2 - Altered phosphodiesterase (PDE)-cyclic AMP (cAMP) activity is frequently associated with anxiety disorders, but current therapies act by reducing neuronal excitability rather than targeting PDE-cAMP-mediated signaling pathways. Here, we report the novel repositioning of anti-cancer MEK inhibitors as anxiolytics in a zebrafish model of anxiety-like behaviors. PDE inhibitors or activators of adenylate cyclase cause behaviors consistent with anxiety in larvae and adult zebrafish. Small-molecule screening identifies MEK inhibitors as potent suppressors of cAMP anxiety behaviors in both larvae and adult zebrafish, while causing no anxiolytic behavioral effects on their own. The mechanism underlying cAMP-induced anxiety is via crosstalk to activation of the RAS-MAPK signaling pathway. We propose that targeting crosstalk signaling pathways can be an effective strategy for mental health disorders, and advance the repositioning of MEK inhibitors as behavior stabilizers in the context of increased cAMP.

AB - Altered phosphodiesterase (PDE)-cyclic AMP (cAMP) activity is frequently associated with anxiety disorders, but current therapies act by reducing neuronal excitability rather than targeting PDE-cAMP-mediated signaling pathways. Here, we report the novel repositioning of anti-cancer MEK inhibitors as anxiolytics in a zebrafish model of anxiety-like behaviors. PDE inhibitors or activators of adenylate cyclase cause behaviors consistent with anxiety in larvae and adult zebrafish. Small-molecule screening identifies MEK inhibitors as potent suppressors of cAMP anxiety behaviors in both larvae and adult zebrafish, while causing no anxiolytic behavioral effects on their own. The mechanism underlying cAMP-induced anxiety is via crosstalk to activation of the RAS-MAPK signaling pathway. We propose that targeting crosstalk signaling pathways can be an effective strategy for mental health disorders, and advance the repositioning of MEK inhibitors as behavior stabilizers in the context of increased cAMP.

U2 - 10.1016/j.chembiol.2015.08.010

DO - 10.1016/j.chembiol.2015.08.010

M3 - Journal article

C2 - 26388333

VL - 22

SP - 1335

EP - 1346

JO - Chemistry and Biology

JF - Chemistry and Biology

SN - 2451-9448

IS - 10

ER -

ID: 154564601

Department of Biomedical Sciences