Enhancement of neurogenesis and cognition through intranasal co-delivery of galanin receptor 2 (GALR2) and neuropeptide Y receptor 1 (NPY1R) agonists: a potential pharmacological strategy for cognitive dysfunctions.

IF 4.7 2区心理学 Q1 BEHAVIORAL SCIENCES

Behavioral and Brain Functions Pub Date : 2024-03-28 DOI:10.1186/s12993-024-00230-5

Raquel Sánchez-Varo, Alexander López-Salas, Rasiel Beltran-Casanueva, Estela Díaz-Sánchez, Jose Erik Alvarez-Contino, Miguel Angel Barbancho-Fernández, Pedro Serrano-Castro, Kjell Fuxe, Dasiel O Borroto-Escuela, Natalia García-Casares, Manuel Narváez

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引用次数: 0

Abstract

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.

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通过鼻内联合给药加拉宁受体 2 (GALR2) 和神经肽 Y 受体 1 (NPY1R) 激动剂增强神经发生和认知能力：治疗认知功能障碍的潜在药理学策略。

背景：空间记忆缺陷和神经元存活率降低是衰老过程中认知能力下降的原因。目前的治疗方法有限，因此需要创新的治疗策略。本研究探讨了鼻内联合给药的加兰宁受体 2（GALR2）和神经肽 Y1 受体（NPY1R）激动剂对成年大鼠空间记忆、神经元存活和分化的综合影响。成年大鼠经鼻内联合给药 GALR2 激动剂 M1145 和 NPY1R 激动剂后，3 周后接受原地取物任务的空间记忆测试。我们分别通过评估BrdU-IR图谱和双皮质素（DCX）标记细胞来检测神经元的存活和分化情况。我们还使用了 GALR2 拮抗剂 M871 来证实 GALR2 在促进细胞生长方面的关键作用：结果：联合给药改善了空间记忆并提高了成熟神经元的存活率。GALR2拮抗剂的无效作用证实了GALR2对细胞增殖的积极作用。治疗可提高DCX标记的新生神经元数量，改变树突形态，增加具有成熟树突的细胞数量：我们的研究结果表明，鼻内联合给药 GALR2 和 NPY1R 激动剂可改善成年大鼠的空间记忆、提高神经元存活率并影响神经元分化。GALR2 的重要作用得到了强调，为治疗认知功能衰退提出了新的潜在治疗策略。

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来源期刊

Behavioral and Brain Functions 医学-行为科学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： A well-established journal in the field of behavioral and cognitive neuroscience, Behavioral and Brain Functions welcomes manuscripts which provide insight into the neurobiological mechanisms underlying behavior and brain function, or dysfunction. The journal gives priority to manuscripts that combine both neurobiology and behavior in a non-clinical manner.