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

Marine 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 chr...

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Published in:	Synapse (New York, N.Y.) Vol. 72; no. 11; pp. e22059 - n/a
Main Authors:	Lax, Neil C., Parker, Stacy‐Ann J., Hilton, Edward J., Seliman, Youstina, Tidgewell, Kevin J., Kolber, Benedict J.
Format:	Journal Article
Language:	English
Published:	United States Wiley Subscription Services, Inc 01-11-2018
Subjects:	Affinity animal models Animals Anti-Anxiety Agents - chemistry Anti-Anxiety Agents - isolation & purification Anti-Anxiety Agents - pharmacology Antidepressive Agents - chemistry Antidepressive Agents - isolation & purification Antidepressive Agents - pharmacology Anxiety Anxiety Disorders - drug therapy Behavior Behavior, Animal - drug effects Biological Products - chemistry Biological Products - isolation & purification Biological Products - pharmacology Central nervous system Column chromatography Comorbidity Cyanobacteria Cyanobacteria - chemistry Cyanobacteria - genetics depression Depressive Disorder - drug therapy Disease Models, Animal Drug Discovery Female Hippocampus - drug effects Male Mental depression Metabolites Mice, Inbred C57BL Mice, Knockout Neuralgia Pain - drug therapy Phylogeny Receptors, Serotonin - genetics Receptors, Serotonin - metabolism rRNA 16S Secondary metabolites Serotonin Antagonists - chemistry Serotonin Antagonists - isolation & purification Serotonin Antagonists - pharmacology serotonin receptor 7 Serotonin receptors Serotonin transporter anxiety animal models drug discovery serotonin receptor 7 cyanobacteria depression behavior
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Summary:	Marine 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 as Leptolyngbya from Las Perlas archipelago in Panama, contained a fraction with noted affinity for the 5‐HT7 receptor (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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0887-4476 1098-2396
DOI:	10.1002/syn.22059