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RNA-Seq data from cortex and hippocampus (post novel object recognition test) of rats in a vagus nerve stimulation study

ABSTRACT: Vagus nerve stimulation (VNS) has been shown to enhance learning and memory, yet the mechanisms behind these enhancements are unknown. We show that VNS altered the hippocampal, cortical, and blood epigenetic transcriptomes in male Sprague Dawley rats whether or not the rats performed a novelty preference behavioral task. In the hippocampus, novelty preference correlated with decreased histone deacetylase 11 (HDAC11), a transcriptional repressor enriched in CA1 cells important for memory consolidation. In the cortex, the immediate early gene (IEG) ARC was increased in VNS rats and correlated with transcription of plasticity genes and epigenetic regulators, including HDAC3. For rats performing the novelty preference task, ARC correlated with performance. Surprisingly, VNS did not significantly reduce transcription of cortical or hippocampal proinflammatory cytokines. However, TNFRSF11B (osteoprotegerin) correlated with novelty preference as well as plasticity, stress–response signaling, and epigenetic regulation in both hippocampus and cortex. Together, our findings provide the first evidence that VNS induces widespread changes in the cognitive epigenetic landscape and specifically affects epigenetic modulators associated with novelty preference, stress–response signaling, memory consolidation, and cortical neural remodeling.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE134309 | GEO | 2019/07/16

REPOSITORIES: GEO

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Project description:Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions. RNA profiles from cognitively unimpaired and impaired aged rats were compared under 2 conditions: spatial learning task and a non-spatial learning task.

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RNA-Seq data from cortex and hippocampus (post novel object recognition test) of rats in a vagus nerve stimulation study

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