RESUMO
Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition and complex behaviors are not well described. Here, we report bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of Nsun2 in the mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease in tRNA m5C levels, resulting in deficits in expression of 70% of tRNAGly isodecoders. Altogether, 1488/5820 proteins changed upon neuronal Nsun2-deficiency, in conjunction with glycine codon-specific defects in translational efficiencies. Loss of Gly-rich proteins critical for glutamatergic neurotransmission was associated with impaired synaptic signaling at PFC pyramidal neurons and defective contextual fear memory. Changes in the neuronal translatome were also associated with a 146% increase in glycine biosynthesis. These findings highlight the methylation sensitivity of glycinergic tRNAs in the adult PFC. Furthermore, they link synaptic plasticity and complex behaviors to epitranscriptomic modifications of cognate tRNAs and the proteomic homeostasis associated with specific amino acids.
Assuntos
Transtorno Depressivo/fisiopatologia , Epigênese Genética/genética , Metiltransferases/genética , Proteoma/metabolismo , RNA de Transferência/genética , Transmissão Sináptica/genética , Animais , Transtorno Depressivo/genética , Transtorno Depressivo/metabolismo , Perfilação da Expressão Gênica/métodos , Metiltransferases/deficiência , Metiltransferases/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Neurônios/metabolismo , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiologia , Proteômica/métodos , RNA de Transferência/metabolismo , Transdução de Sinais/genéticaRESUMO
BACKGROUND/OBJECTIVE: We aimed to determine the prevalence of anxiety, depression symptomatology and suicidal ideation among patients with acne and the impact of this skin condition on the quality of life in Lithuania. METHODS: The mental health of patients with acne was assessed using an adapted Hospital Anxiety and Depression Scale, the Dermatology Quality of Life Index, questions about characteristics of acne. The study was authorized by the Regional Biomedical Research Ethics Committee. RESULTS: A total of 255 responders of 324 patients with acne included (84.4%) were assessed. 56.1% of the responders had comorbid anxiety, depression symptomatology or suicidal ideation related to acne. Among them, 38.4% had anxiety symptoms, 23.1% had depression symptoms and 12.9% had suicidal thoughts due to acne. About 96.5% of the responders had a reduced quality of life due to acne. CONCLUSION: More than a half of the patients with acne who participated at the study had comorbid emotional disorders. Anxiety was the most prevalent sign, 1.7-fold more prevalent than depression and threefold more prevalent than suicidal ideation. Depression was prevalent in more than every fourth responder and suicidal ideation afflicted every eighth acne patient. More than 90% of the patients had impaired life quality.
