Jahanshahi Mehrdad, Elyasi Leila, Nikmahzar Emsehgol
Department of Anatomy, Faculty of Medicine, Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
Basic Clin Neurosci. 2025 Jan-Feb;16(1):19-30. doi: 10.32598/bcn.2024.93.6. Epub 2025 Jan 1.
Glutamate plays a significant role in synaptic plasticity, which is important for learning and memory. Astrocytes are an important part of glial cells or neuroglia. They are involved in neuroinflammation and are key in maintaining glutamine/glutamate homeostasis. As astrocytes provide vital support to neurons in pathological conditions, we aimed to evaluate the effect of hippocampal astrocyte ablation induced by microinjection of L-α-aminoadipic acid (L-α-AAA) in this study. We intend to assess memory, anxiety, and the density of glial fibrillary acidic protein-immunoreactive (GFAP-ir) astrocytes in the hippocampus.
A total of 21 adult male Wistar rats were randomly assigned to control, vehicle, and experimental groups. L-α-AAA was injected into their hippocampal CA1 subfield for 3 days. Then, their memory was evaluated by an inhibitory passive avoidance test, and anxiety-related behavior using an elevated plus maze apparatus. Hippocampal sections were immunostained for GFAP, and the density of GFAP-ir astrocytes was evaluated.
Microinjection of L-α-AAA into the CA1 subfield of the hippocampus significantly decreased the step-through latency time in the passive avoidance test, decreased time spent in the open arm, and increased time spent in the closed arm in the elevated plus maze test. Also, the administration of L-α-AAA significantly declined the density of GFAP-ir astrocytes in the hippocampus.
Inhibition of astrocytes impaired memory and increased anxiety-like behavior in male rats. Hence, the current study confirmed hippocampal astrocytes' key role in memory and anxiety-like behavior, which can be considered in future therapeutic strategies.
谷氨酸在突触可塑性中发挥着重要作用，而突触可塑性对学习和记忆至关重要。星形胶质细胞是神经胶质细胞的重要组成部分。它们参与神经炎症反应，并且在维持谷氨酰胺/谷氨酸稳态方面起着关键作用。由于星形胶质细胞在病理条件下为神经元提供重要支持，因此在本研究中，我们旨在评估通过微量注射L-α-氨基己二酸（L-α-AAA）诱导海马星形胶质细胞消融的效果。我们打算评估记忆、焦虑以及海马中胶质纤维酸性蛋白免疫反应性（GFAP-ir）星形胶质细胞的密度。
总共21只成年雄性Wistar大鼠被随机分配到对照组、溶剂组和实验组。将L-α-AAA注入它们的海马CA1亚区，持续3天。然后，通过抑制性被动回避试验评估它们的记忆，并使用高架十字迷宫装置评估与焦虑相关的行为。对海马切片进行GFAP免疫染色，并评估GFAP-ir星形胶质细胞的密度。
向海马CA1亚区微量注射L-α-AAA显著缩短了被动回避试验中的穿通潜伏期时间，减少了在高架十字迷宫试验中开放臂停留的时间，并增加了在封闭臂停留的时间。此外，给予L-α-AAA显著降低了海马中GFAP-ir星形胶质细胞的密度。
星形胶质细胞的抑制损害了雄性大鼠的记忆并增加了焦虑样行为。因此，本研究证实了海马星形胶质细胞在记忆和焦虑样行为中的关键作用，这在未来的治疗策略中可以加以考虑。
