背景:空间记忆缺陷和神经元存活减少导致衰老过程中的认知能力下降。目前的治疗方法有限,强调创新治疗策略的必要性。这项研究探索了鼻内共给药甘丙肽受体2(GALR2)和神经肽Y1受体(NPY1R)激动剂的联合作用,他们的神经益处得到认可,关于空间记忆,神经元存活,和成年大鼠的分化。在将GALR2激动剂M1145和NPY1R激动剂鼻内共递送至成年大鼠后,3周后用原位对象任务测试空间记忆。我们通过评估BrdU-IR谱和doublecortin(DCX)标记的细胞来检查神经元的存活和分化,分别。我们还使用了GALR2拮抗剂M871来证实GALR2在促进细胞生长中的关键作用。
结果:共同给药改善了空间记忆并提高了成熟神经元的存活率。GALR2在细胞增殖中的积极作用由其拮抗剂的无效作用证实。该治疗增强了DCX标记的新生神经元并改变了树突形态,随着成熟树突的增加细胞。
结论:我们的结果表明,鼻内共同递送GALR2和NPY1R激动剂可改善空间记忆,提高神经元的存活率,并影响成年大鼠的神经元分化。强调了GALR2的重要作用,提出了新的潜在的认知能力下降的治疗策略。
BACKGROUND: Spatial memory deficits and reduced neuronal survival contribute to cognitive decline seen in the aging process. Current treatments are limited, emphasizing the need for innovative therapeutic strategies. This research explored the combined effects of intranasally co-administered galanin receptor 2 (GALR2) and neuropeptide Y1 receptor (NPY1R) agonists, recognized for their neural benefits, on spatial memory, neuronal survival, and differentiation in adult rats. After intranasal co-delivery of the GALR2 agonist M1145 and a NPY1R agonist to adult rats, spatial memory was tested with the object-in-place task 3 weeks later. We examined neuronal survival and differentiation by assessing BrdU-IR profiles and doublecortin (DCX) labeled cells, respectively. We also used the GALR2 antagonist M871 to confirm GALR2\'s crucial role in promoting cell growth.
RESULTS: Co-administration improved spatial memory and increased the survival rate of mature neurons. The positive effect of GALR2 in cell proliferation was confirmed by the nullifying effects of its antagonist. The treatment boosted DCX-labeled newborn neurons and altered dendritic morphology, increasing cells with mature dendrites.
CONCLUSIONS: Our results show that intranasal co-delivery of GALR2 and NPY1R agonists improves spatial memory, boosts neuronal survival, and influences neuronal differentiation in adult rats. The significant role of GALR2 is emphasized, suggesting new potential therapeutic strategies for cognitive decline.