The ubiquitin proteasome system (UPS) is a primary mechanism through which proteins are degraded in cells. UPS activity in the dorsal hippocampus (DH) is necessary for multiple types of memory, including object memory, in male rodents. However, sex differences in DH UPS activation after fear conditioning suggest that other forms of learning may also differentially regulate DH UPS activity in males and females. Here, we examined markers of UPS activity in the synaptic and cytoplasmic fractions of DH and medial prefrontal cortex (mPFC) tissue collected 1 h following object training. In males, training increased phosphorylation of proteasomal subunit Rpt6, 20S proteasome activity, and the amount of PSD-95 in the DH synaptic fraction, as well as proteasome activity in the mPFC synaptic fraction. In females, training did not affect measures of UPS or synaptic activity in the DH synaptic fraction or in either mPFC fraction but increased Rpt6 phosphorylation in the DH cytoplasmic fraction. Overall, training-induced UPS activity was greater in males than in females, greater in the DH than in the mPFC, and greater in synaptic fractions than in cytosol. These data suggest that object training drives sex-specific alterations in UPS activity across brain regions and subcellular compartments important for memory.

中文翻译：

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训练诱导的雄性和雌性小鼠背侧海马和内侧前额叶皮层泛素蛋白酶体系统活性的性别差异

泛素蛋白酶体系统 (UPS) 是细胞中蛋白质降解的主要机制。雄性啮齿动物背侧海马体 (DH) 的 UPS 活动对于多种类型的记忆（包括物体记忆）是必需的。然而，恐惧调节后 DH UPS 激活的性别差异表明，其他形式的学习也可能对男性和女性的 DH UPS 活动进行差异调节。在这里，我们检查了对象训练后 1 小时收集的 DH 和内侧前额皮质 (mPFC) 组织的突触和细胞质部分中的 UPS 活性标记。在雄性中，训练增加了蛋白酶体亚基 Rpt6 的磷酸化、20S 蛋白酶体活性、DH 突触部分中的 PSD-95 量以及 mPFC 突触部分中的蛋白酶体活性。在女性中，训练不会影响 DH 突触部分或 mPFC 部分中的 UPS 或突触活动测量，但会增加 DH 细胞质部分中的 Rpt6 磷酸化。总体而言，训练引起的 UPS 活性在男性中高于女性，在 DH 中高于在 mPFC 中，在突触部分中高于在胞浆中。这些数据表明，物体训练会驱动对记忆很重要的大脑区域和亚细胞区室的 UPS 活动发生性别特异性改变。