Cyanobacterial extract with serotonin receptor subtype 7 (5‐HT7R) affinity modulates depression and anxiety‐like behavior in mice

Neil C. Lax; Stacy‐Ann J. Parker; Edward J. Hilton; Youstina Seliman; Kevin J. Tidgewell; Benedict J. Kolber

doi:10.1002/syn.22059

journal article Aug 21, 2018

Cyanobacterial extract with serotonin receptor subtype 7 (5‐HT7R) affinity modulates depression and anxiety‐like behavior in mice

Neil C. Lax Stacy‐Ann J. Parker Edward J. Hilton Youstina Seliman Kevin J. Tidgewell Benedict J. Kolber

Synapse Vol. 72 No. 11 · Wiley

View at Publisher Save 10.1002/syn.22059

Abstract

AbstractMarine cyanobacteria represent a unique source in the field of drug discovery due to the secondary metabolites they produce and the structural similarity these compounds have to endogenous mammalian receptor ligands. A series of cyanobacteria were subjected to extraction, fractionation by column chromatography and screened for affinity against CNS targets with a focus on serotonin receptors (5‐HTRs). Out of 276 fractions screened, 21% had activity at 5‐HTRs and/or the 5‐HT transporter (SERT). One sample, a cyanobacterium identified by 16S rRNA sequencing asLeptolyngbyafrom Las Perlas archipelago in Panama, contained a fraction with noted affinity for the 5‐HT7receptor (5‐HT7R). This fraction (DUQ0002I) was screened via intracerebroventricular (ICV) injections in mice using depression and anxiety assays including the forced swim, tail suspension, elevated zero maze, and light‐dark preference tests. DUQ0002I decreased depression and anxiety‐like behaviors in males and did not have effects in 5‐HT7R knockout or female mice. Administration of DUQ0002I to the CA1 of the hippocampus induced antidepression‐like, but not anxiolytic‐like behaviors. Testing of further purified materials showed no behavioral effects, leading us to hypothesize that the behavioral effects are likely caused by a synergistic effect between multiple compounds in the fraction. Finally, DUQ0002I was used in a model of neuropathic pain with comorbid depression (spared nerve injury—SNI). DUQ0002I had a similar antidepressant effect in animals with SNI, suggesting a role for the 5‐HT7R in the development of comorbid pain and depression. These results demonstrate the potential that cyanobacterial metabolites have in the field of neuropharmacognosy.

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References

Details

Published: Aug 21, 2018
Vol/Issue: 72(11)
License: View

Authors

N

Neil C. Lax

Department of Biological Sciences Duquesne University Pittsburgh Pennsylvania; Chronic Pain Research Consortium Duquesne University Pittsburgh Pennsylvania

S

Stacy‐Ann J. Parker

Mylan School of Pharmacy Duquesne University Pittsburgh Pennsylvania; Chronic Pain Research Consortium Duquesne University Pittsburgh Pennsylvania

E

Edward J. Hilton

Department of Biological Sciences Duquesne University Pittsburgh Pennsylvania; Chronic Pain Research Consortium Duquesne University Pittsburgh Pennsylvania

Y

Youstina Seliman

Department of Biological Sciences Duquesne University Pittsburgh Pennsylvania; Chronic Pain Research Consortium Duquesne University Pittsburgh Pennsylvania

K

Kevin J. Tidgewell

Mylan School of Pharmacy Duquesne University Pittsburgh Pennsylvania; Chronic Pain Research Consortium Duquesne University Pittsburgh Pennsylvania

B

Benedict J. Kolber

Department of Biological Sciences Duquesne University Pittsburgh Pennsylvania; Chronic Pain Research Consortium Duquesne University Pittsburgh Pennsylvania

Funding

National Institute of Mental Health

University of North Carolina

Fogarty International Center Award: 2U01TW006634‐06

Smithsonian Institution Award: 16S

Instituto de Investigação Científica Tropical

American Pain Society

Duquesne University

National Center for Complementary and Integrative Health Award: R15AT008060

Cite This Article

Neil C. Lax, Stacy‐Ann J. Parker, Edward J. Hilton, et al. (2018). Cyanobacterial extract with serotonin receptor subtype 7 (5‐HT7R) affinity modulates depression and anxiety‐like behavior in mice. Synapse, 72(11). https://doi.org/10.1002/syn.22059

Cyanobacterial extract with serotonin receptor subtype 7 (5‐HT7R) affinity modulates depression and anxiety‐like behavior in mice

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