ABSTRACT
BACKGROUND: Emerging research implicates ethanol (EtOH)-induced epigenetic modifications in regulating gene expression and EtOH consumption. However, consensus on specific epigenetic modifications induced by EtOH has not yet emerged, making it challenging to identify mechanisms and develop targeted treatments. We hypothesized that chronic intermittent EtOH (CIE) induces persistent changes in histone modifications across the cerebral cortex (CCx), nucleus accumbens (NAc), and prefrontal cortex (PFC), and that these histone modifications are altered in a knock-in mouse strain with altered sensitivity to EtOH. METHODS: C57BL/6J (B6) mice and α1SHLA knockin mice on a B6 background were exposed to 16 h of vapor EtOH or room air followed by 8 h of room air for 4 consecutive days and sacrificed at multiple time points up to 72 h following exposure. Histone modifications were assessed using Western blot and dot blot. RT-qPCR was used to study expression of chromatin modifying enzymes in NAc and PFC. RESULTS: In NAc, CIE significantly increased acetylation of histone subunit H3 at lysine 9 (H3K9ac) but not lysine 14 (H3K14ac) or lysine 27 (H3K27ac). In PFC, CIE significantly increased H3K9ac but not H3K14 or H3K27ac. There were no significant changes at 8 or 72 h after EtOH exposure in either NAc or PFC. CIE was also associated with increased expression of Kat2b, Kat5, and Tet1 in NAc but not PFC. In CCx, CIE had a significant effect on levels of H3K18ac; there was also a significant effect of the α1SHLA mutation on levels of H3K27me3, H3K14ac, and H3K18ac as well as a trend for H3S10pK14ac. CONCLUSIONS: The EtOH-induced histone modifications observed were transient and varied significantly between brain regions. A genetic mutation that altered sensitivity to EtOH was associated with altered induction of histone modifications during CIE. These results have implications for studying EtOH-induced histone modifications and EtOH sensitivity.
ABSTRACT
OBJECTIVE: To examine the course of health risk behaviors (HRBs) during a 3-year period after a parent's death in bereaved youth compared with nonbereaved youth (control subjects). DESIGN: A longitudinal population-based study. SETTING: Bereaved families were recruited through coroner records and by advertisement. Control families were recruited using random-digit dialing and by advertisement. PARTICIPANTS: Two hundred forty parentally bereaved offspring were compared with 183 nonbereaved control offspring. MAIN EXPOSURE: Sudden parental death due to accident, suicide, or sudden disease-related (natural) death. MAIN OUTCOME MEASURES: The sum of the total number of HRBs at a clinically significant frequency threshold assessed 9, 21, and 33 months after the parent's death. RESULTS: The bereaved group showed a higher number of HRBs over time compared with the nonbereaved group (univariate effect sizes, 0.22-0.52; P < .04), even after taking into account correlates of bereavement and of HRBs, such as youth aggression, as well as antisocial and anxiety disorders of the deceased parent. CONCLUSIONS: Parental bereavement is associated with higher HRBs in youth over time, even after controlling for other covariates associated with bereavement and HRBs. Clinicians should be aware that bereaved youth may be vulnerable to HRBs. Further work is warranted on interventions to attenuate the negative effect of bereavement on HRBs.
