An Antisense Oligonucleotide Leads to Suppressed Transcription of Hdac2 and Long-Term Memory Enhancement.

Knockout of the memory suppressor gene histone deacetylase 2 (Hdac2) in mice elicits cognitive enhancement, and drugs that block HDAC2 have potential as therapeutics for disorders affecting memory. Currently available HDAC2 catalytic activity inhibitors are not fully isoform specific and have short half-lives. Antisense oligonucleotides (ASOs) are drugs that elicit extremely long-lasting, specific inhibition through base pairing with RNA targets.

Cognition-Enhancing Vagus Nerve Stimulation Alters the Epigenetic Landscape.

Vagus nerve stimulation (VNS) has been shown to enhance learning and memory, yet the mechanisms behind these enhancements are unknown. Here, we present evidence that epigenetic modulation underlies VNS-induced improvements in cognition. We show that VNS enhances novelty preference (NP); alters the hippocampal, cortical, and blood epigenetic transcriptomes; and epigenetically modulates neuronal plasticity and stress-response signaling genes in male Sprague Dawley rats.