Sex differences in training-induced activity of the ubiquitin proteasome system in the dorsal hippocampus and medial prefrontal cortex of male and female mice.

Sex differences in training-induced activity of the ubiquitin proteasome system in the dorsal hippocampus and medial prefrontal cortex of male and female mice.
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DOI:
10.1101/lm.053492.121
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发表时间:
2022-09
期刊:
影响因子:
2
通讯作者:
Frick, Karyn M. M.
Frick, Karyn M. M.
中科院分区:
医学4区
文献类型:
--
作者:
Beamish, Sarah B. B.;Gross, Kellie S. S.;Anderson, McKenna M. M.;Helmstetter, Fred J. J.;Frick, Karyn M. M.

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泛素蛋白酶体系统(UPS)是蛋白质在细胞中降解的主要机制。在雄性啮齿动物中,背侧海马(DH)中的UPS活性对于多种类型的记忆(包括物体记忆)是必需的。然而,恐惧条件反射后DH UPS激活的性别差异表明,其他形式的学习也可能差异调节男性和女性的DH UPS活性。在这里,我们研究了标记物的UPS活动的突触和细胞质部分的DH和内侧前额叶皮层(mPFC)组织收集1小时后对象的培训。在男性中,训练增加了蛋白酶体亚基Rpt 6的磷酸化,20 S蛋白酶体活性,以及DH突触部分中PSD-95的量,以及mPFC突触部分中的蛋白酶体活性。在女性中,训练并没有影响测量的UPS或突触活动的DH突触部分或在任何mPFC部分,但增加Rpt 6磷酸化的DH细胞质部分。总的来说,训练诱导的UPS活动是男性比女性,更大的DH比在mPFC,更大的突触分数比在胞质溶胶。这些数据表明,物体训练驱动了对记忆重要的大脑区域和亚细胞区室的UPS活动的性别特异性改变。
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.
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