Ibn Lahmar Andaloussi Zineb, Taghzouti Khalid, Abboussi Oualid
Physiology and Physiopathology Team, Faculty of Sciences, Genomic of Human Pathologies Research Centre, Mohammed V University in Rabat, Morocco.
Institute of Academic Anaesthesia, Division of Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
Int J Dev Neurosci. 2019 Feb;72:48-54. doi: 10.1016/j.ijdevneu.2018.11.007. Epub 2018 Nov 23.
Chronic cannabinoid exposure during adolescence in male rats induces chronic cognitive and emotional impairments. However, the impact of this form of exposure on offspring vulnerability to stress is unknown. The aim of this study was to evaluate the behavioural and epigenetic effects of stress in the offspring of male rats whose fathers were exposed to cannabinoids during adolescence. Male adolescent offspring of Win55,212-2 (1.2 mg/kg) treated rats were exposed during one week to variable stressors and subjected to behavioural tests of anxiety and episodic-like memory, followed by an assessment of global DNA methylation and expression of DNA methyltransferases enzymes DNMT1 and DNMT3a mRNA in the prefrontal cortex. Stress exposure induced a significant anxiogenic-like effect but did not affect the episodic-like memory in the offspring of Win55,212-2 exposed fathers in comparison to the offspring of non-exposed fathers. These behavioural changes were subsequent to a significant increase in global DNA methylation and DNMT1 and DNMTa3 transcription in the prefrontal cortex. These data suggest that the deleterious effect of chronic exposure to cannabinoids during adolescence are not limited to the exposed individuals but may increase the vulnerability to stress-induced anxiety in the offspring and alter their epigenetic programming.
青春期雄性大鼠长期接触大麻素会导致慢性认知和情绪障碍。然而，这种接触形式对后代应激易感性的影响尚不清楚。本研究的目的是评估青春期父亲接触过大麻素的雄性大鼠后代中应激的行为和表观遗传效应。对经Win55,212 - 2（1.2毫克/千克）处理的大鼠的雄性青春期后代进行为期一周的可变应激源暴露，并进行焦虑和情景样记忆的行为测试，随后评估前额叶皮质中的整体DNA甲基化以及DNA甲基转移酶DNMT1和DNMT3a mRNA的表达。与未接触过大麻素的父亲的后代相比，应激暴露在经Win55,212 - 2处理的父亲的后代中诱导了显著的焦虑样效应，但未影响情景样记忆。这些行为变化发生在前额叶皮质中整体DNA甲基化以及DNMT1和DNMTa3转录显著增加之后。这些数据表明，青春期长期接触大麻素的有害影响不仅限于接触者本身，还可能增加后代对应激诱导焦虑的易感性，并改变其表观遗传程序。
