Department of Morphological Sciences and Teratology, Adelson School of Medicine, Ariel University, Ariel 4076414, Israel.
Department Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 4076414, Israel.
Int J Mol Sci. 2022 Oct 7;23(19):11898. doi: 10.3390/ijms231911898.
Reduction in the levels of monoamines, such as serotonin and dopamine in the brain, were reported in patients and animals with depression. SAMe, a universal methyl donor and an epigenetic modulator, is successfully used as an adjunct treatment of depression. We previously found that prenatal treatment with SAMe of Submissive (Sub) mice that serve as a model for depression alleviated many of the behavioral depressive symptoms. In the present study, we treated pregnant Sub mice with 20 mg/kg of SAMe on days 12-15 of gestation and studied the levels of monoamines and the expression of genes related to monoamines metabolism in their prefrontal cortex (PFC) at the age of 3 months. The data were compared to normal saline-treated Sub mice that exhibit depressive-like symptoms. SAMe increased the levels of serotonin in the PFC of female Sub mice but not in males. The levels of 5-HIAA were not changed. SAMe increased the levels of dopamine and of DOPAC in males and females but increased the levels of HVA only in females. The levels of norepinephrine and its metabolite MHPG were unchanged. SAMe treatment changed the expression of several genes involved in the metabolism of these monoamines, also in a sex-related manner. The increase in several monoamines induced by SAMe in the PFC may explain the alleviation of depressive-like symptoms. Moreover, these changes in gene expression more than 3 months after treatment probably reflect the beneficial effects of SAMe as an epigenetic modulator in the treatment of depression.
研究发现，抑郁症患者和动物大脑中的单胺类物质（如血清素和多巴胺）水平降低。SAMe 是一种通用的甲基供体和表观遗传调节剂，成功地被用作抑郁症的辅助治疗方法。我们之前发现，对作为抑郁症模型的顺从（Sub）小鼠进行产前 SAMe 处理可以缓解许多行为性抑郁症状。在本研究中，我们在妊娠第 12-15 天对 Sub 孕鼠用 20mg/kg 的 SAMe 进行处理，并在 3 个月大时研究其前额皮质（PFC）中单胺类物质的水平和与单胺代谢相关基因的表达。将这些数据与表现出抑郁样症状的生理盐水处理的 Sub 小鼠进行比较。SAMe 增加了雌性 Sub 小鼠 PFC 中 5-羟色胺的水平，但对雄性没有影响。5-HIAA 的水平没有变化。SAMe 增加了雄性和雌性多巴胺及其代谢产物 DOPAC 的水平，但仅增加了雌性 HVA 的水平。去甲肾上腺素及其代谢产物 MHPG 的水平不变。SAMe 处理以性别相关的方式改变了参与这些单胺代谢的几个基因的表达。SAMe 在 PFC 中诱导的几种单胺类物质的增加可能解释了抑郁样症状的缓解。此外，这些基因表达的变化在治疗 3 个月后出现，可能反映了 SAMe 作为表观遗传调节剂治疗抑郁症的有益效果。
