Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, 149 Thirteenth Street, Room 2401, Charlestown, MA, 02129-2000, USA.
Department of Neurology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, Japan.
Biol Sex Differ. 2024 Nov 21;15(1):93. doi: 10.1186/s13293-024-00670-8.
A-kinase anchoring protein 12 (AKAP12) is a key scaffolding protein that regulates cellular signaling by anchoring protein kinase A (PKA) and other signaling molecules. While recent studies suggest an important role for AKAP12 in the brain, including cognitive functions, its role in middle-aged mice and potential sex differences are not fully understood. Therefore, this study investigated the effects of AKAP12 on cognitive and exploratory behavior in middle-aged mice, focusing on sex differences. Cognitive function was assessed using the spontaneous Y-maze test and the novel object recognition test (NORT). No significant sex differences in cognitive function were found in middle-aged C57BL/6J mice; however, female mice showed greater exploratory behavior during the NORT. In addition, both middle-aged male and female Akap12 knockout (KO) mice performed similarly to wild-type (WT) mice in the Y-maze test, but had lower discrimination indices in the NORT, suggesting a potential role for AKAP12 in short-term memory. Notably, exploratory behavior was suppressed in female Akap12 KO mice compared to WT mice, whereas male Akap12 KO mice did not show this effect. There were no significant differences in movement distance and velocity during the Y-maze test and NORT between WT and KO mice of either sex. These results indicate that AKAP12 affects cognitive function and exploratory behavior in middle-aged mice and that these effects differ between sexes.
A-激酶锚定蛋白 12（AKAP12）是一种关键的支架蛋白，通过锚定蛋白激酶 A（PKA）和其他信号分子来调节细胞信号转导。虽然最近的研究表明 AKAP12 在大脑中具有重要作用，包括认知功能，但它在中年小鼠中的作用及其潜在的性别差异尚不完全清楚。因此，本研究旨在探讨 AKAP12 对中年小鼠认知和探索行为的影响，重点关注性别差异。使用自发 Y 迷宫测试和新物体识别测试（NORT）评估认知功能。在中年 C57BL/6J 小鼠中，未发现认知功能存在显著的性别差异；然而，雌性小鼠在 NORT 中表现出更大的探索行为。此外，中年雄性和雌性 Akap12 敲除（KO）小鼠在 Y 迷宫测试中的表现与野生型（WT）小鼠相似，但在 NORT 中的辨别指数较低，表明 AKAP12 可能在短期记忆中发挥作用。值得注意的是，与 WT 小鼠相比，雌性 Akap12 KO 小鼠的探索行为受到抑制，而雄性 Akap12 KO 小鼠则没有表现出这种效应。在 Y 迷宫测试和 NORT 中，WT 和 KO 小鼠的运动距离和速度在两性之间均无显著差异。这些结果表明，AKAP12 影响中年小鼠的认知功能和探索行为，并且这些影响在性别之间存在差异。
