Centro de Ciências da Saúde Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil.
Departamento de Fisiologia e Farmacologia, UFSM, Santa Maria, RS, Brazil.
Mol Neurobiol. 2019 Sep;56(9):6239-6250. doi: 10.1007/s12035-019-1522-5. Epub 2019 Feb 11.
Depression is a common psychiatric disease which pharmacological treatment relieves symptoms, but still far from ideal. Tactile stimulation (TS) has shown beneficial influences in neuropsychiatric disorders, but the mechanism of action is not clear. Here, we evaluated the TS influence when applied on adult female rats previously exposed to a reserpine-induced depression-like animal model. Immediately after reserpine model (1 mg/kg/mL, 1×/day, for 3 days), female Wistar rats were submitted to TS (15 min, 3×/day, for 8 days) or not (unhandled). Imipramine (10 mg/kg/mL) was used as positive control. After behavioral assessments, animals were euthanized to collect plasma and prefrontal cortex (PFC). Behavioral observations in the forced swimming test, splash test, and sucrose preference confirmed the reserpine-induced depression-like behavior, which was reversed by TS. Our findings showed that reserpine increased plasma levels of adrenocorticotropic hormone and corticosterone, decreased brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B, and increased proBDNF immunoreactivity in the PFC, which were also reversed by TS. Moreover, TS reestablished glial fibrillary acidic protein and glucocorticoid receptor levels, decreased by reserpine in PFC, while glial cell line-derived neurotrophic factor was increased by TS per se. Our outcomes are showing that TS applied in adulthood exerts a beneficial influence in depression-like behaviors, modulating the HPA axis and regulating neurotrophic factors more effectively than imipramine. Based on this, our proposal is that TS, in the long term, could be considered a new therapeutic strategy for neuropsychiatric disorders improvement in adult life, which may represent an interesting contribution to conventional pharmacological treatment.
抑郁症是一种常见的精神疾病,药物治疗可以缓解症状,但仍远不理想。触觉刺激(TS)已显示出对神经精神疾病的有益影响,但作用机制尚不清楚。在这里,我们评估了在先前暴露于利血平诱导的抑郁样动物模型的成年雌性大鼠中应用 TS 的影响。利血平模型(1mg/kg/mL,每天 1 次,共 3 天)后立即,雌性 Wistar 大鼠接受 TS(15 分钟,每天 3 次,共 8 天)或不接受处理(未处理)。丙咪嗪(10mg/kg/mL)用作阳性对照。行为评估后,处死动物以收集血浆和前额叶皮层(PFC)。强迫游泳试验、飞溅试验和蔗糖偏好行为观察证实了利血平诱导的抑郁样行为,而 TS 逆转了这种行为。我们的研究结果表明,利血平增加了血浆中促肾上腺皮质激素和皮质酮的水平,降低了脑源性神经营养因子(BDNF)和原肌球蛋白受体激酶 B 的水平,并增加了 PFC 中的前体 BDNF 免疫反应性,这些也被 TS 逆转。此外,TS 重建了 PFC 中由利血平降低的神经胶质纤维酸性蛋白和糖皮质激素受体水平,而 TS 本身增加了胶质细胞源性神经营养因子。我们的研究结果表明,成年期应用 TS 对抑郁样行为产生有益影响,调节 HPA 轴并比丙咪嗪更有效地调节神经营养因子。基于此,我们的建议是,TS 可能代表着一种改善成年生活中神经精神疾病的新治疗策略,这可能是对传统药物治疗的一个有趣贡献。