Abstract:
:miR-132 and miR-212 are structurally-related microRNAs that are expressed from the same non-coding transcript. Accumulating evidence has shown that the dysregulation of these microRNAs contributes to aberrant neuronal plasticity and gene expression in the mammalian brain. Consistent with this, altered expression of miR-132 is associated with a number of affect-related psychiatric disorders. Here, we tested the functional contribution of the miR-132/212 locus to the development of stress-related and anxiety-like behaviors. Initially, we tested whether expression from the miR-132/212 locus is altered by stress-inducing paradigms. Using a 5-h acute-stress model, we show that both miR-132 and miR-212 are increased more than two-fold in the WT murine hippocampus and amygdala, whereas after a 15 day chronic-stress paradigm, expression of both miR-132 and miR-212 are upregulated more than two-fold within the amygdala but not in the hippocampus. Next, we used a tetracycline-inducible miR-132 overexpression mouse model and a miR-132/212 conditional knockout (cKO) mouse model to examine whether dysregulation of miR-132/212 expression alters basal anxiety-like behaviors. Interestingly, in both the miR-132 overexpression and cKO lines, significant increases in anxiety-like behaviors were detected. Importantly, suppression of transgenic miR-132 expression (via doxycycline administration) mitigated the anxiety-related behaviors. Further, expression of Sirt1 and Pten-two miR-132 target genes that have been implicated in the regulation of anxiety-were differentially regulated in the hippocampus and amygdala of miR-132/212 conditional knockout and miR-132 transgenic mice. Collectively, these data raise the prospect that miR-132 and miR-212 may play a key role in the modulation of stress responsivity and anxiety.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Aten S,Page CE,Kalidindi A,Wheaton K,Niraula A,Godbout JP,Hoyt KR,Obrietan Kdoi
10.1016/j.neuropharm.2018.10.020subject
Has Abstractpub_date
2019-01-01 00:00:00pages
256-270eissn
0028-3908issn
1873-7064pii
S0028-3908(18)30804-9journal_volume
144pub_type
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