TIAM Rac1-associated GEF 2 short-form protein (TIAM2S) is abundant in specific brain tissues, especially in the hippocampus, a brain region critical for processing and consolidation of spatial memory. However, how TIAM2S plasticizes the microstructure and circuits of the hippocampus to shape spatial memory as a neuroplastic regulator during aging remains to be determined. In this study, transgenic mice overexpressing human TIAM2S protein (TIAM2S-TG mice) were included, and interdisciplinary approaches, such as spatial memory tests and multiparametric magnetic resonance imaging sequences, were conducted to determine the role and the mechanism of TIAM2S in age-related spatial memory deficits. Despite no changes in their neural and glial markers and neuropathological hallmark expression of the hippocampus, behavioral tests showed that the TIAM2S-TG mice, and not wild-type (WT) mice, developed spatial memory impairment at 18 months old. The T2-weighted and diffusion tensor image analyses were performed to further study the possible role of TIAM2S overexpression in altering the hippocampal structure or neuronal circlets of the mice, increasing their vulnerability to developing spatial memory deficits during aging. The results revealed that the 12-month-old TIAM2S-TG mice had hippocampal dysplasticity, with larger volume, increased fiber numbers, and changed mean fractional anisotropy compared to those in the age-matched WT mice. The fiber tractography analysis exhibited significantly attenuated structural connectivity between the hippocampus and medial prefrontal cortex in the TIAM2S-TG mice. In conclusion, overexpression of TIAM2S, a detrimental factor affecting hippocampus plasticity, causes attenuation of the connectivity within hippocampus–mPFC circuits, leading to age-related spatial memory impairment.

中文翻译：

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TIAM2S 是海马-内侧前额叶皮层网络的关键调节因子，其过表达会导致与年龄相关的空间记忆障碍


TIAM Rac1 相关的 GEF 2 短型蛋白 （TIAM2S） 在特定脑组织中丰富，尤其是在海马体中，海马体是处理和巩固空间记忆的关键大脑区域。然而，TIAM2S 如何在衰老过程中塑化海马体的微观结构和回路以形成空间记忆作为神经可塑性调节剂仍有待确定。本研究纳入过表达人 TIAM2S 蛋白的转基因小鼠 （TIAM2S-TG 小鼠），并采用空间记忆测试和多参数磁共振成像序列等跨学科方法，以确定 TIAM2S 在年龄相关空间记忆缺陷中的作用和机制。尽管它们的神经和神经胶质标志物以及海马体的神经病理学标志表达没有变化，但行为测试表明，TIAM2S-TG 小鼠，而不是野生型 （WT） 小鼠，在 18 个月大时出现空间记忆障碍。进行 T2 加权和弥散张量图像分析，以进一步研究 TIAM2S 过表达在改变小鼠海马结构或神经元环中可能的作用，从而增加它们在衰老过程中发展空间记忆缺陷的脆弱性。结果显示，与年龄匹配的 WT 小鼠相比，12 月龄的 TIAM2S-TG 小鼠具有海马发育不良，体积更大，纤维数量增加，平均各向异性分数发生变化。纤维束造影分析显示 TIAM2S-TG 小鼠海马和内侧前额叶皮层之间的结构连接显着减弱。 总之，TIAM2S 的过表达是影响海马可塑性的有害因素，会导致海马-mPFC 回路内的连接衰减，从而导致与年龄相关的空间记忆障碍。