Department of Medical Care, School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Department of Neurology & Psychology, Shenzhen Traditional Chinese Medicine Hospital, Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.
Exp Gerontol. 2024 Jun 1;190:112432. doi: 10.1016/j.exger.2024.112432. Epub 2024 Apr 12.
The beneficial effect of social interaction in mitigating the incidence of post-stroke depression (PSD) and ameliorating depressive symptoms has been consistently demonstrated through preclinical and clinical studies. However, the underlying relationship with oxytocin requires further investigation. In light of this, the present study aimed to explore the protective effect of pair housing on the development of PSD and the potential relationship with oxytocin receptors. The PSD model was induced by middle cerebral artery occlusion (MCAO) for 50 min, followed by 4-week isolated housing and restrained stress. Subsequently, each mouse in the pair-housing group (PH) was pair-housed with an isosexual healthy partner. Another group was continuously administrated fluoxetine (10 mg/Kg, i.p, once a day) for 3 weeks. To elucidate the potential role of oxytocin, we subjected pair-housed PSD mice to treatment with an oxytocin receptor (OXTR) antagonist (L368,889) (5 mg/Kg, i.p, once a day) for 3 weeks. At 31 to 32 days after MCAO, anxiety- and depressive-like behaviors were assessed using sucrose consumption, forced swim test, and tail-suspension test. The results showed that pair housing significantly improved post-stroke depression to an extent comparable to that of fluoxetine treatment. Furthermore, pair housing significantly decreased corticosterone in serum, increasing OXT mRNA expression in the hypothalamus. Treatment with L368,889 essentially reversed the effect of pair housing, with no discernible sex differences apart from changes in body weight. Pair housing increased hippocampal serotonin (5-HT), but treatment with L368,889 had no significant impact. Additionally, pair housing effectively reduced the number of reactive astrocytes and increased Nissl's body in the cortex and hippocampal CA3 regions. Correspondingly, treatment with L368,889 significantly reversed the changes in the Nissl's body and reactive astrocytes. Moreover, pair housing downregulated mRNA levels of TNF-α, IL-1β, and IL-6 in the cortex caused by PSD, which was also reversed by treatment with L368,889. In conclusion, pair housing protects against the development of PSD depending on OXT and OXTR in the brain, with no significant divergence based on sex. These findings provide valuable insights into the potential of social interaction and oxytocin as therapeutic targets for PSD. Further research into the underlying mechanisms of these effects may contribute to the development of novel treatments for PSD.
社交互动对减轻中风后抑郁（PSD）的发生和改善抑郁症状有有益的影响，这一作用已被临床前和临床研究证实。然而，与催产素的潜在关系仍需要进一步研究。有鉴于此，本研究旨在探讨配对饲养对 PSD 发展的保护作用及其与催产素受体的潜在关系。通过大脑中动脉闭塞（MCAO）诱导 PSD 模型 50 分钟，然后进行 4 周的单独饲养和束缚应激。随后，配对饲养组（PH）中的每只小鼠与一只同性健康的伴侣配对饲养。另一组连续 3 周每天腹腔注射氟西汀（10mg/Kg）。为了阐明催产素的潜在作用，我们对配对饲养的 PSD 小鼠进行了催产素受体（OXTR）拮抗剂（L368,889）（5mg/Kg，腹腔注射，每天一次）治疗 3 周。在 MCAO 后 31 至 32 天，使用蔗糖消耗、强迫游泳试验和悬尾试验评估焦虑和抑郁样行为。结果表明，配对饲养显著改善了中风后的抑郁，程度与氟西汀治疗相当。此外，配对饲养显著降低了血清中的皮质酮，增加了下丘脑的 OXT mRNA 表达。L368,889 的治疗基本上逆转了配对饲养的作用，除了体重变化外，没有明显的性别差异。配对饲养增加了海马体中的 5-羟色胺（5-HT），但 L368,889 的治疗没有显著影响。此外，配对饲养有效地减少了皮质和海马 CA3 区的反应性星形胶质细胞数量，并增加了尼氏体的数量。相应地，L368,889 的治疗显著逆转了尼氏体和反应性星形胶质细胞的变化。此外，配对饲养下调了 PSD 引起的皮质 TNF-α、IL-1β 和 IL-6 的 mRNA 水平，而 L368,889 的治疗也逆转了这一作用。总之，配对饲养通过大脑中的催产素和 OXTR 来预防 PSD 的发展，而且没有明显的性别差异。这些发现为社交互动和催产素作为 PSD 治疗靶点提供了有价值的见解。对这些作用的潜在机制的进一步研究可能有助于开发 PSD 的新疗法。
