Anesthesia promotes acute expression of genes related to Alzheimer's disease and latent tau aggregation in transgenic mouse models of tauopathy.

BACKGROUND: Exposure to anesthesia in the elderly might increase the risk of dementia. Although the mechanism underlying the association is uncertain, anesthesia has been shown to induce acute tau hyperphosphorylation in preclinical models. We sought to investigate the impact of anesthesia on gene expression and on acute and long-term changes in tau biochemistry in transgenic models of tauopathy in order to better understand how anesthesia influences the pathophysiology of dementia. METHODS: We exposed mice with over-expressed human mutant tau (P301L and hyperdopaminergic COMTKO/P301L) to two hours of isoflurane and compared anesthetized mice to controls at several time points. We evaluated tau hyperphosphorylation with quantitative high-sensitivity enzyme-linked immunosorbent assay and performed differential expression and functional transcriptome analyses following bulk mRNA-sequencing. RESULTS: Anesthesia induced acute hyperphosphorylation of tau at epitopes related to Alzheimer's disease (AD) in both P301L-based models. Anesthesia was associated with differential expression of genes in the neurodegenerative pathways (e.g., AD-risk genes ApoE and Trem2) and thermogenesis pathway, which is related to both mammalian hibernation and tau phosphorylation. One and three months after anesthesia, hyperphosphorylated tau aggregates were increased in the anesthetized mice. CONCLUSIONS: Anesthesia may influence the expression of AD-risk genes and induce biochemical changes in tau that promote aggregation even after single exposure. Further preclinical and human studies are necessary to establish the relevance of our transcriptomic and biochemical findings in these preclinical models to the pathogenesis of dementia following anesthesia. TRIAL REGISTRATION: Not applicable.

Parenting style and mental disorders in a nationally representative sample of US adolescents.

PURPOSE: We examined associations between parenting style and past-year mental disorders in a nationally representative cross-sectional survey of US adolescents and whether the associations differed by adolescent demographic characteristics. METHODS: The sample included 6483 adolescents aged 13-18 years who were interviewed for a full range of DSM-IV mental disorders. Parenting style was assessed by adolescent-reported maternal and paternal care and control using items from the Parental Bonding Instrument. We controlled for socio-demographics, parental history of mental disorders, stressful life events, sexual violence, inter-parental conflict, and household composition. We also tested for two-way interactions between parental care and control and adolescent age, sex, and race/ethnicity. RESULTS: In adjusted models, high maternal care was associated with lower odds of depressive, eating, and behavioral disorders, and high maternal control was associated with greater odds of depressive, anxiety, eating, and behavioral disorders. High paternal care was associated with lower odds of social phobia and alcohol abuse/dependence. High paternal control was associated with greater odds of agoraphobia and alcohol abuse/dependence but with lower odds of attention-deficit/hyperactivity disorder. Associations of maternal and paternal control with anxiety disorders and substance abuse/dependence differed by sex. High paternal care was associated with lower odds of anxiety disorders only among Hispanics and non-Hispanic blacks. CONCLUSIONS: Perceived parental care and control were associated with adolescent mental disorders after controlling for multiple potential confounders. Differential patterns of association were found according to adolescent sex and race/ethnicity. Findings have implications for prevention and intervention programs that incorporate familial contextual factors.