DESCRIPTION:
To examine the cellular mechanism(s) by which HDAC5, a transcriptional repressor, limits cue-induced reinstatement of heroin seeking in D1-MSNs, we infused in the NAc of D1-Cre or D2-Cre rats a mixture of AAV2-DIO-HDAC5-3SA together with AAV2-viral translating ribosomal affinity purification (vTRAP), which allows for Cre-dependent expression of L10a-GFP and subsequent enrichment of actively translating mRNAs in a cell-type–specific manner (19). Since coinfusion of the two viruses produced >90% coexpression of GFP and HDAC5 (SI Appendix, Fig. S4A), this allowed us to assess cell-specific effects of HDAC5-3SA on gene expression. Following qPCR validation of vTRAP enrichment from NAc tissues from the D1-Cre or D2-Cre rats (Fig. 4A), we isolated ribosome-associated transcripts from both cell types in the presence or absence of AAV2-DIO-HDAC5-3SA after at least 3 wk of AAV expression. Due to the relatively low yields of mRNAs isolated from Cre-expressing cells in the vTRAP pulldown approach, we analyzed differentially expressed genes (DEGs) using gene microarrays. These data suggest that HDAC5-3SA functions predominantly to reduce target gene expression and in D2-Cre animals (data presented here), the majority (55%) of transcripts were downregulated. We also found that HDAC5 functions in NAc D1-MSNs to limit cue-reinstated heroin seeking, but in D2-MSNs to limit heroin-reinstated drug seeking. DEGs were calculated using criteria of false discovery rate (FDR) ≤ 0.05 and log2 (fold change) ≥ |0.3|.
LABEL:
DEG effect of HDAC5 in rat NAc D2-MSNs reduced heroin-seeking_qvalue
SCORE TYPE:
Q-Value
THRESHOLD:
<= 0.5
GENES IN THRESHOLD:
1991
DATE ADDED:
DATE UPDATED:
SPECIES:
AUTHORS:
TITLE:
JOURNAL:
ABSTRACT:
Genes in threshold: 1991
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