SAMP8 小鼠神经发生和年龄相关认知衰退的拯救：转化生长因子-α 的作用,Aging Cell

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SAMP8 小鼠神经发生和年龄相关认知衰退的拯救：转化生长因子-α 的作用
Aging Cell ( IF 8.0 ) Pub Date : 2023-05-12 , DOI: 10.1111/acel.13829
Ricardo Gómez-Oliva _{1,

2} , Sergio Martínez-Ortega _{1,

2} , Isabel Atienza-Navarro _{1,

2} , Samuel Domínguez-García _{1,

2} , Carlos Bernal-Utrera _{2,

3} , Noelia Geribaldi-Doldán _{2,

4} , Cristina Verástegui _{2,

4} , Abdellah Ezzanad _{2,

5} , Rosario Hernández-Galán _{2,

5} , Pedro Nunez-Abades _{2,

6} , Monica Garcia-Alloza _{1,

2} , Carmen Castro _{1,

2}

Affiliation

神经病理性衰老与记忆障碍和认知能力下降有关，影响多个大脑区域，包括海马齿状回 (DG) 的神经源性生态位。在健康的大脑中，稳态机制调节 DG 内的神经发生，以促进神经干细胞 (NSC) 持续生成神经元。然而，衰老会减少激活的神经干细胞的数量并减少新生成的神经元的数量。促进 DG 神经发生的策略可能会改善老年人的认知能力，从而开发出预防老年人神经系统疾病进展的治疗方法。我们的工作旨在发现可用于设计预防大脑衰老的神经系统影响的药物的靶向分子。我们使用 SAMP8 小鼠作为神经病理学衰老模型，研究年龄对海马神经发生的影响。我们发现，6 个月大的 SAMP8 小鼠的情景记忆和空间记忆受损；与此同时，在该模型中，神经母细胞和神经元的生成减少，星形胶质细胞的生成增加。我们工作的新颖性在于，用转化生长因子-α (TGFα) 靶向分子治疗 SAMP8 小鼠可以防止观察到的缺陷，积极调节神经发生并改善认知能力。该化合物促进 TGFα 在体外和体内的释放，并激活由该生长因子启动的信号通路。我们得出的结论是，这种刺激神经发生的化合物可能有助于抵消病理性衰老的神经效应。

"点击查看英文标题和摘要"

Rescue of neurogenesis and age-associated cognitive decline in SAMP8 mouse: Role of transforming growth factor-alpha

Neuropathological aging is associated with memory impairment and cognitive decline, affecting several brain areas including the neurogenic niche of the dentate gyrus of the hippocampus (DG). In the healthy brain, homeostatic mechanisms regulate neurogenesis within the DG to facilitate the continuous generation of neurons from neural stem cells (NSC). Nevertheless, aging reduces the number of activated neural stem cells and diminishes the number of newly generated neurons. Strategies that promote neurogenesis in the DG may improve cognitive performance in the elderly resulting in the development of treatments to prevent the progression of neurological disorders in the aged population. Our work is aimed at discovering targeting molecules to be used in the design of pharmacological agents that prevent the neurological effects of brain aging. We study the effect of age on hippocampal neurogenesis using the SAMP8 mouse as a model of neuropathological aging. We show that in 6-month-old SAMP8 mice, episodic and spatial memory are impaired; concomitantly, the generation of neuroblasts and neurons is reduced and the generation of astrocytes is increased in this model. The novelty of our work resides in the fact that treatment of SAMP8 mice with a transforming growth factor-alpha (TGFα) targeting molecule prevents the observed defects, positively regulating neurogenesis and improving cognitive performance. This compound facilitates the release of TGFα in vitro and in vivo and activates signaling pathways initiated by this growth factor. We conclude that compounds of this kind that stimulate neurogenesis may be useful to counteract the neurological effects of pathological aging.

更新日期：2023-05-12

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