Relationships between lateral hypothalamic orexin circuits and electroacupuncture-induced mitigation of anxiety in a post-traumatic stress disorder model.
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引用次数: 0
Abstract
Background: Post-traumatic stress disorder (PTSD) is a distressing condition characterized by persistent negative affective states. Electroacupuncture (EA) is a clinically recognized, safe, and efficacious treatment for managing negative emotions associated with PTSD. However, the neural circuits involved in the effects of EA on these emotional disturbances remain unclear.
Methods: A modified single prolonged stress (MSPS) procedure was used to develop a mouse model presenting PTSD-like anxiety-related behaviors (ALBs). Adeno-associated viral tracing showed excitatory synaptic transmission from the lateral hypothalamus (LH) to the bed nucleus of the stria terminalis (BNST). By combining anterograde and retrograde tracing, ex vivo electrophysiological analysis, and chemogenetic modulation, the study elucidated the modulatory role of the LHorexin-BNST circuit in regulating ALBs under the influence of EA.
Results: EA significantly reduced ALBs in MSPS mice, as evaluated by open field tests and elevated plus mazes (all P < 0.05). MSPS mice showed reduced c-Fos-positive neuronal activity in the LH orexin after behavioral testing, which was reversed by EA treatment (P < 0.01). EA upregulated orexin type 2 receptor protein expression in the LH and activated LH-BNST neural projections (all P < 0.05). Orexin-A potentiated spontaneous excitatory postsynaptic currents and action potential firing in BNST glutamatergic neurons. Chemogenetic inhibition of the LHorexin-BNST circuit suppressed EA-induced anxiolytic behaviors and reduced neuronal activity in LH orexinergic and BNST glutamatergic populations (all P < 0.05). Similarly, chemogenetic activation alleviated ALBs (P < 0.05) and enhanced neuronal activity (P < 0.01), simulating EA's effects.
Conclusion: EA regulates synaptic activity in BNST glutamatergic neurons, identifying the LHorexin-BNST glutamatergic circuit as a key mediator of EA-induced anxiolytic effects and a possible therapeutic target for PTSD management.
期刊介绍：
The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.
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