Early life stress increases risk for depression. Here we establish a "two-hit" stress model in mice wherein stress at a specific postnatal period increases susceptibility to adult social defeat stress and causes long-lasting transcriptional alterations that prime the ventral tegmental area (VTA)-a brain reward region-to be in a depression-like state. We identify a role for the developmental transcription factor orthodenticle homeobox 2 (Otx2) as an upstream mediator of these enduring effects. Transient juvenile-but not adult-knockdown of Otx2 in VTA mimics early life stress by increasing stress susceptibility, whereas its overexpression reverses the effects of early life stress. This work establishes a mechanism by which early life stress encodes lifelong susceptibility to stress via long-lasting transcriptional programming in VTA mediated by Otx2.
This research output has an Altmetric Attention Score of 252. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 July 2024.
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#181,985
of 33,934,236 outputs
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#5,122
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#3,016
of 346,061 outputs
Outputs of similar age from Science
#98
of 1,197 outputs
Altmetric has tracked 33,934,236 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 93,653 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 65.8. This one has done particularly well, scoring higher than 94% of its peers.
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We're also able to compare this research output to 1,197 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 91% of its contemporaries.
