■重度抑郁症(MDD)是一种普遍且使人衰弱的疾病,由于当前治疗的有限功效和不利影响,需要新的治疗策略。我们探索了甘丙肽受体2(GALR2)和神经肽Y1受体(NPYY1R)激动剂,一起工作,可以促进脑细胞生长并增加大鼠的抗抑郁作用。这提出了治疗重度抑郁症(MDD)的新方法。
■在受控的实验室环境中,成年幼稚Sprague-Dawley大鼠直接进入脑室,一种称为脑室内(ICV)给药的方法,与GALR2激动剂(M1145),NPYY1R激动剂,两者,或与GALR2拮抗剂(M871)组合。主要结果指标包括长期神经元存活,分化,和行为。
■M1145和NPYY1R激动剂的共同施用显着增强了腹侧齿状回中的神经元存活和成熟,脑源性神经营养因子(BDNF)表达显着增加。这种神经源性效应与抗抑郁样效应有关,结果被M871部分逆转。
■GALR2和NPYY1R激动剂共同促进大鼠海马神经发生并发挥抗抑郁样作用,无不良结局,强调他们对MDD的治疗潜力。该研究依赖于动物模型和脑室内给药,值得进一步的临床探索以证实这些有希望的结果。
UNASSIGNED: Major Depressive Disorder (MDD) is a prevalent and debilitating condition, necessitating novel therapeutic strategies due to the limited efficacy and adverse effects of current treatments. We explored how galanin receptor 2 (GALR2) and Neuropeptide Y1 Receptor (NPYY1R) agonists, working together, can boost brain cell growth and increase antidepressant-like effects in rats. This suggests new ways to treat Major Depressive Disorder (MDD).
UNASSIGNED: In a controlled laboratory setting, adult naive Sprague-Dawley rats were administered directly into the brain\'s ventricles, a method known as intracerebroventricular (ICV) administration, with GALR2 agonist (M1145), NPYY1R agonist, both, or in combination with a GALR2 antagonist (M871). Main outcome measures included long-term neuronal survival, differentiation, and behavioral.
UNASSIGNED: Co-administration of M1145 and NPYY1R agonist significantly enhanced neuronal survival and maturation in the ventral dentate gyrus, with a notable increase in Brain-Derived Neurotrophic Factor (BDNF) expression. This neurogenic effect was associated with an antidepressant-like effect, an outcome partially reversed by M871.
UNASSIGNED: GALR2 and NPYY1R agonists jointly promote hippocampal neurogenesis and exert antidepressant-like effects in rats without adverse outcomes, highlighting their therapeutic potential for MDD. The study\'s reliance on an animal model and intracerebroventricular delivery warrants further clinical exploration to confirm these promising results.