University of Wisconsin-Milwaukee, Department of Psychology, Milwaukee, WI, USA.
University of Wisconsin-Milwaukee, Department of Psychology, Milwaukee, WI, USA; Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Horm Behav. 2024 Sep;165:105618. doi: 10.1016/j.yhbeh.2024.105618. Epub 2024 Aug 23.
Infusion of 17β-estradiol (E) into the dorsal hippocampus (DH) of ovariectomized (OVX) mice enhances memory consolidation, an effect that depends on rapid phosphorylation of extracellular signal-regulated kinase (ERK) and Akt. Astrocytic glutamate transporter 1 (GLT-1) modulates neurotransmission via glutamate uptake from the synaptic cleft. However, little is known about the contribution of DH astrocytes, and astrocytic glutamate transport, to the memory-enhancing effects of E. This study was designed to test whether DH astrocytes contribute to estrogenic modulation of memory consolidation by determining the extent to which DH GLT-1 is necessary for E to enhance memory in object recognition and object placement tasks and trigger rapid phosphorylation events in DH astrocytes. OVX female mice were bilaterally cannulated into the DH or the DH and dorsal third ventricle (ICV). Post-training DH infusion of the GLT-1 inhibitor dihydrokainic acid (DHK) dose-dependently impaired memory consolidation in both tasks. Moreover, the memory-enhancing effects of ICV-infused E in each task were blocked by DH DHK infusion. E increased p42 ERK and Akt phosphorylation in DH astrocytes, and these effects were blocked by DHK. Results suggest the necessity of DH GLT-1 activity for object and spatial memory consolidation, and for E to enhance consolidation of these memories and to rapidly activate cell signaling in DH astrocytes. Findings indicate that astrocytic function in the DH of OVX females is necessary for memory formation and is regulated by E and suggest an essential role for DH astrocytic GLT-1 activity in the memory-enhancing effects of E.
往去卵巢（OVX）小鼠的背侧海马（DH）中输注 17β-雌二醇（E）可增强记忆巩固，这种作用依赖于细胞外信号调节激酶（ERK）和 Akt 的快速磷酸化。星形胶质细胞谷氨酸转运体 1（GLT-1）通过从突触间隙摄取谷氨酸来调节神经传递。然而，对于 E 增强记忆的作用，DH 星形胶质细胞和星形胶质细胞谷氨酸转运的贡献知之甚少。本研究旨在通过确定 DH GLT-1 对于 E 在物体识别和物体放置任务中增强记忆以及触发 DH 星形胶质细胞中快速磷酸化事件的程度，来检验 DH 星形胶质细胞是否有助于雌激素对记忆巩固的调节。OVX 雌性小鼠双侧脑室内（DH）或 DH 和第三脑室（ICV）进行套管插入。训练后，DH 内源性 GLT-1 抑制剂二氢克酸（DHK）的输注剂量依赖性地损害了两种任务的记忆巩固。此外，DH 内源性 DHK 输注阻断了 ICV 输注 E 在每种任务中的增强记忆作用。E 增加了 DH 星形胶质细胞中 p42 ERK 和 Akt 的磷酸化，而这些作用被 DHK 阻断。结果表明，DH GLT-1 活性对于物体和空间记忆巩固是必需的，并且 E 增强这些记忆的巩固，并快速激活 DH 星形胶质细胞中的细胞信号转导。研究结果表明，OVX 雌性小鼠 DH 中的星形胶质细胞功能对于记忆形成是必需的，并受 E 调节，并且 DH 星形胶质细胞 GLT-1 活性在 E 的增强记忆作用中起重要作用。
