An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model.
An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model.
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DOI：
10.1371/journal.pone.0032662
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sohrabji F
中科院分区：
文献类型：
--
作者：
Selvamani A;Sathyan P;Miranda RC;Sohrabji F
We previously showed that middle-aged female rats sustain a larger infarct following experimental stroke as compared to younger female rats, and paradoxically, estrogen treatment to the older group is neurotoxic. Plasma and brain insulin-like growth factor-1 (IGF-1) levels decrease with age. However, IGF-1 infusion following stroke, prevents estrogen neurotoxicity in middle-aged female rats. IGF1 is neuroprotective and well tolerated, but also has potentially undesirable side effects. We hypothesized that microRNAs (miRNAs) that target the IGF-1 signaling family for translation repression could be alternatively suppressed to promote IGF-1-like neuroprotection. Here, we report that two conserved IGF pathway regulatory microRNAs, Let7f and miR1, can be inhibited to mimic and even extend the neuroprotection afforded by IGF-1. Anti-mir1 treatment, as late as 4 hours following ischemia, significantly reduced cortical infarct volume in adult female rats, while anti-Let7 robustly reduced both cortical and striatal infarcts, and preserved sensorimotor function and interhemispheric neural integration. No neuroprotection was observed in animals treated with a brain specific miRNA unrelated to IGF-1 (anti-miR124). Remarkably, anti-Let7f was only effective in intact females but not males or ovariectomized females indicating that the gonadal steroid environment critically modifies miRNA action. Let7f is preferentially expressed in microglia in the ischemic hemisphere and confirmed in ex vivo cultures of microglia obtained from the cortex. While IGF-1 was undetectable in microglia harvested from the non-ischemic hemisphere, IGF-1 was expressed by microglia obtained from the ischemic cortex and was further elevated by anti-Let7f treatment. Collectively these data support a novel miRNA-based therapeutic strategy for neuroprotection following stroke.
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DOI：
10.1038/jcbfm.2008.157
发表时间：
2009-04
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.5
作者：
Hutchison, Emmette R.;Okun, Eitan;Mattson, Mark P.
通讯作者：
Mattson, Mark P.
影响因子：
14.9
作者：
Bhat-Nakshatri P;Wang G;Collins NR;Thomson MJ;Geistlinger TR;Carroll JS;Brown M;Hammond S;Srour EF;Liu Y;Nakshatri H
通讯作者：
Nakshatri H
DOI：
10.1073/pnas.0710263105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Hebert, Sebastien S.;Horre, Katrien;De Strooper, Bart
通讯作者：
De Strooper, Bart
影响因子：
9.9
作者：
Borasio, GD;Robberecht, W;Dobbins, T
通讯作者：
Dobbins, T