Methamphetamine Induces Sex-Dependent Changes in Gene Expression in Male and Female Hearts

Male and female rats received daily injections of saline or methamphetamine for 10 days. Changes in gene expression were assessed by RNA sequencing either 24 hours or 30 days following the last injection. Methamphetamine induced changes in the myocardial transcriptome were significantly greater in female hearts than male hearts both in terms of the number of genes affected and the magnitude of the changes. The largest changes in female hearts involved genes that regulate the circadian clock (Dbp, Per3, Per2, BMal1, and Npas2) which is known to impact myocardial sensitivity to ischemia. These genes were unaffected by methamphetamine in male hearts. All changes in gene expression identified at day 11 returned to baseline by day 30. These data demonstrate that female rats are more sensitive than males to methamphetamine-induced changes in the myocardial transcriptome and that methamphetamine does not induce changes in myocardial transcription that persist long term after exposure to the drug has been discontinued. Gene expression profiling of cardiac tissue of male and female rats following treatment with methamphetamine or saline, with and without 30 days of abstinence following treatment.

本研究对雌雄大鼠每日予以生理盐水或甲基苯丙胺（methamphetamine）注射，连续给药10天。于末次给药后24小时或30天，采用RNA测序（RNA sequencing）检测基因表达变化。甲基苯丙胺诱导的心肌转录组（myocardial transcriptome）表达变化，在雌性大鼠心脏中无论是受影响基因的数量还是变化幅度，均显著高于雄性大鼠。雌性大鼠心脏中变化最显著的基因为调控昼夜节律钟（circadian clock）的基因（包括Dbp、Per3、Per2、BMal1及Npas2），已知这类基因可影响心肌对缺血的敏感性；而在雄性大鼠心脏中，甲基苯丙胺并未对这类基因产生影响。末次给药后第11天检测到的所有基因表达变化，均在第30天时恢复至基线水平。上述实验数据表明，雌性大鼠较雄性大鼠对甲基苯丙胺诱导的心肌转录组表达变化更为敏感；且在停药后，甲基苯丙胺不会诱导产生长期持续的心肌转录变化。本数据集包含经甲基苯丙胺或生理盐水处理的雌雄大鼠心脏组织的基因表达谱，涵盖处理后即刻与处理后戒断30天两种采样条件。