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

Neil R. Smalheiser, Giovanni Lugli, Hooriyah S. Rizavi, Hui Zhang, Vetle Ingvald Torvik, Ghanshyam N. Pandey, John M. Davis, Yogesh Dwivedi

Research output: Contribution to journalArticle

Abstract

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 5-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.

Original languageEnglish (US)
Pages (from-to)1315-1325
Number of pages11
JournalInternational Journal of Neuropsychopharmacology
Volume14
Issue number10
DOIs
StatePublished - Nov 1 2011

Fingerprint

Learned Helplessness
MicroRNAs
Shock
Brain
Down-Regulation
Gene Regulatory Networks
Frontal Lobe
Sprague Dawley Rats
Seeds
Gene Expression
Control Groups
Messenger RNA

Keywords

  • Depression
  • gene expression
  • learned helplessness
  • microRNA
  • rat brain

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

MicroRNA expression in rat brain exposed to repeated inescapable shock : Differential alterations in learned helplessness vs. non-learned helplessness. / Smalheiser, Neil R.; Lugli, Giovanni; Rizavi, Hooriyah S.; Zhang, Hui; Torvik, Vetle Ingvald; Pandey, Ghanshyam N.; Davis, John M.; Dwivedi, Yogesh.

In: International Journal of Neuropsychopharmacology, Vol. 14, No. 10, 01.11.2011, p. 1315-1325.

Research output: Contribution to journalArticle

Smalheiser, Neil R. ; Lugli, Giovanni ; Rizavi, Hooriyah S. ; Zhang, Hui ; Torvik, Vetle Ingvald ; Pandey, Ghanshyam N. ; Davis, John M. ; Dwivedi, Yogesh. / MicroRNA expression in rat brain exposed to repeated inescapable shock : Differential alterations in learned helplessness vs. non-learned helplessness. In: International Journal of Neuropsychopharmacology. 2011 ; Vol. 14, No. 10. pp. 1315-1325.
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AU - Zhang, Hui

AU - Torvik, Vetle Ingvald

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