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MicroRNA expression in rat brain exposed to repeated inescapable shock: differential alterations in learned helplessness vs. non-learned helplessness

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journal contribution
posted on 06.12.2013 by Neil R. Smalheiser, Giovanni Lugli, Hooriyah S. Rizavi, Hui Zhang, Vetle I. Torvik, Ghanshyam N. Pandey, John M. Davis, Yogesh Dwivedi
MicroRNA (miRNA) expression was measured within frontal cortex of male Holtzman rats subjected to repeated inescapable shocks at days 1 and 7, tested for learned helplessness (LH) at days 2 and 8, and sacrificed at day 15. We compared rats that did vs. did not exhibit LH, as well as rats that were placed in the apparatus and tested for avoidance but not given shocks (tested controls, TC). Non-learned helpless (NLH) rats showed a robust adaptive miRNA response to inescapable shock whereas LH rats showed a markedly blunted response. One set of 12 miRNAs showed particularly large, significant down-regulation in NLH rats relative to tested controls (mir-96, 141, 182, 183, 183*, 298, 200a, 200a*, 200b, 200b*, 200c, 429). These were encoded at a few shared polycistronic loci, suggesting that the down-regulation was coordinately controlled at the level of transcription. Most of these miRNAs are enriched in synaptic fractions. Moreover, almost all of these share 5k-seed motifs with other members of the same set, suggesting that they will hit similar or overlapping sets of target mRNAs. Finally, half of this set is predicted to hit Creb1 as a target. We also identified a core miRNA co-expression module consisting of 36 miRNAs that are highly correlated with each other across individuals of the LH group (but not in the NLH or TC groups). Thus, miRNAs participate in the alterations of gene expression networks that underlie the normal (NLH) as well as aberrant (LH) response to repeated shocks.

Funding

This research was supported by grants from NIMH (R01MH 68777, R21MH081099; R01MH082802; R21MH091509), American Foundation for Suicide Prevention, and Stanley Medical Research Institute.

History

Publisher Statement

This is a copy of an article published in the International Journal of Neuropsychopharmacology © 2011 Cambridge University Press. The final publication is available at http://journals.cambridge.org/action/displayJournal?jid=PNP doi: 10.1017/S1461145710001628

Citation

Smalheiser NR, Lugli G, Rizavi HS, Zhang H, Torvik VI, Pandey GN, Davis JM, Dwivedi Y. MicroRNA expression in rat brain exposed to repeated inescapable shock: differential alterations in learned helplessness vs. non-learned helplessness. International Journal of Neuropsychopharmacology. 2011 Nov;14(10):1315-25. doi: 10.1017/S1461145710001628.

Publisher

Cambridge University Press

Language

en_US

issn

1469-5111

Issue date

01/11/2011

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