L-α-aminoadipic Acid-induced Astrocytes Inhibition in the Hippocampal CA1 Region, Anxiety-like Behavior, and Memory Impairment.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.