MicroRNA 135 is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity.

Abstract:

:The link between dysregulated serotonergic activity and depression and anxiety disorders is well established, yet the molecular mechanisms underlying these psychopathologies are not fully understood. Here, we explore the role of microRNAs in regulating serotonergic (5HT) neuron activity. To this end, we determined the specific microRNA "fingerprint" of 5HT neurons and identified a strong microRNA-target interaction between microRNA 135 (miR135), and both serotonin transporter and serotonin receptor-1a transcripts. Intriguingly, miR135a levels were upregulated after administration of antidepressants. Genetically modified mouse models, expressing higher or lower levels of miR135, demonstrated major alterations in anxiety- and depression-like behaviors, 5HT levels, and behavioral response to antidepressant treatment. Finally, miR135a levels in blood and brain of depressed human patients were significantly lower. The current results suggest a potential role for miR135 as an endogenous antidepressant and provide a venue for potential treatment and insights into the onset, susceptibility, and heterogeneity of stress-related psychopathologies.

journal_name

Neuron

journal_title

Neuron

authors

Issler O,Haramati S,Paul ED,Maeno H,Navon I,Zwang R,Gil S,Mayberg HS,Dunlop BW,Menke A,Awatramani R,Binder EB,Deneris ES,Lowry CA,Chen A

doi

10.1016/j.neuron.2014.05.042

subject

Has Abstract

pub_date

2014-07-16 00:00:00

pages

344-360

issue

2

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(14)00486-3

journal_volume

83

pub_type

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