Uncovering the Role of Astrocytes in Mediating Surgery-Induced Anxiety: A Study
Astrocytes play a crucial role in mediating surgery-induced anxiety in mice through modulating GABAergic signaling in the zona incerta (ZI). Recent study aimed to investigate how reactive astrocytes in the ZI contribute to surgery-induced anxiety and the potential mechanisms involved. The researchers used a multimodal approach involving behavioral tests, fiber photometric recordings, electrophysiological recordings, and chemogenetic and optogenetic manipulations to study this phenomenon.
Astrocyte Activation and Anxiety
Mice that underwent laparotomy showed increased anxiety-like behavior, along with abnormal activation of astrocytes in the ZI. Manipulating astrocyte activation in the ZI alleviated anxiety-like behavior in the surgery group. The surgery group displayed increased extrasynaptic GABA levels and decreased GABA transporter expression, leading to the inactivation of GABAergic neurons. This highlighted the role of reactive astrocytes in regulating GABA homeostasis to mediate surgery-induced anxiety in mice.
Neurological Complications and Astrocyte Function
Surgery can lead to neurological dysfunction and complications, including anxiety, insomnia, and cognitive decline. Neuroinflammation is a key factor in these issues, and the transformation of astrocytes into reactive astrocytes plays a significant role. Dysregulation of GABA homeostasis, particularly through GAT-3 downregulation in astrocytes, was identified as a critical mechanism driving surgery-induced anxiety.
GAT-3 Expression and GABAergic Neurons
Further investigations revealed that upregulating GAT-3 expression in astrocytes rescued GABAergic neuron activity and alleviated anxiety-like behavior in operative mice. Additionally, activating the ZI GABA /median raphe nucleus pathway significantly reduced anxiety-like behavior induced by surgery. The findings emphasized the importance of the ZI GABAergic pathway in modulating anxiety-related behavior and potentially serving as a therapeutic target for surgery-induced anxiety. The study provided insights into the molecular and neural circuit mechanisms underlying surgery-induced anxiety and highlighted the intricate interplay between reactive astrocytes, GABA regulation, and neuronal activity in the ZI. Targeting astrocytic GAT-3 and modulating the ZI GABA /MRN pathway emerged as promising strategies for mitigating surgery-induced anxiety and improving cognitive outcomes. While the study identified key mechanisms involved, further research is warranted to elucidate the specific subtypes and circuits within the ZI contributing to anxiety and to explore potential therapeutic interventions for neurological complications following surgery.
Key Points
- Astrocytes in the zona incerta (ZI) play a crucial role in mediating surgery-induced anxiety in mice through modulating GABAergic signaling.
- Reactive astrocytes in the ZI contribute to surgery-induced anxiety by affecting GABA homeostasis, leading to increased extrasynaptic GABA levels and decreased GABA transporter expression.
- Manipulating astrocyte activation in the ZI can alleviate anxiety-like behavior in mice that underwent surgery, highlighting the role of reactive astrocytes in regulating anxiety-related behaviors.
- Neurological complications following surgery, such as anxiety, insomnia, and cognitive decline, involve neuroinflammation and the transformation of astrocytes into reactive astrocytes. - Dysregulation of GABA homeostasis, particularly through GAT-3 downregulation in astrocytes, is a critical mechanism driving surgery-induced anxiety.
- Upregulating GAT-3 expression in astrocytes can rescue GABAergic neuron activity and alleviate anxiety-like behavior in operative mice, suggesting a potential therapeutic target for surgery-induced anxiety.
Reference-
Kun Tong et al. (2024). Reactive Astrocytes Mediate Postoperative Surgery-Induced Anxiety Through Modulation Of GABAergic Signalling In The Zona Incerta Of Mice.. *British Journal Of Anaesthesia*. https://doi.org/10.1016/j.bja.2024.08.043.
