RESUMO
Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR1 and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries illuminate the nuanced functions and intricate regulatory mechanisms of RNA editing within the human brain.
RESUMO
Anhedonia - the reduced ability to experience or respond to pleasure - is an important symptom domain for many psychiatric disorders. It is particularly relevant to depression and other mood disorders and it is a diagnostic criterion of a major depressive episode. Developing safe and effective pharmacological interventions for anhedonia is a critical public health need. The current chapter will review the state of the field with respect to both the efficacy of currently available pharmacotherapies for anhedonia and the recent clinical research focusing on new brain targets, including the kappa-opioid receptor and the KCNQ2/3 receptors. The evidence for anti-anhedonic effects of ketamine and psychedelic agents will be reviewed, as well.
Assuntos
Transtorno Depressivo Maior , Ketamina , Anedonia , Encéfalo , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Ketamina/farmacologia , Ketamina/uso terapêutico , Transtornos do Humor/tratamento farmacológico , RecompensaRESUMO
This Article was originally published without the correct Supplemental Table file (Table S1 was missing). In total, there are seven Supplemental Tables, and six were in the original submission. Furthermore, Fig. 1 was misplaced in the main text; it was embedded in the manuscript file even before the results section. Both issues have now been fixed in the HTML and PDF versions of this Article.