The locus coeruleus-dorsal hippocampal CA1 pathway is involved in depression-induced perioperative neurocognitive disorders in adult mice.

Autor: Zhang K; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.; Tianjin Institute of Anesthesiology, Tianjin, China., Chang Q; School of Pharmacy, Tianjin Medical University, Tianjin, China., Li F; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.; Tianjin Institute of Anesthesiology, Tianjin, China., Li Y; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.; Tianjin Institute of Anesthesiology, Tianjin, China., Ding R; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China., Yu Y; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.; Tianjin Institute of Anesthesiology, Tianjin, China.
Jazyk: angličtina
Zdroj: CNS neuroscience & therapeutics [CNS Neurosci Ther] 2024 Feb; Vol. 30 (2), pp. e14406. Date of Electronic Publication: 2023 Aug 14.
DOI: 10.1111/cns.14406
Abstrakt: Background: Patients undergoing surgical anesthesia increasingly suffer from preoperative depression. Clinical studies have shown that depression is a risk factor for perioperative neurocognitive disorders (PNDs) in elder patients. However, the underlying mechanism, especially at the neural circuit level, remains poorly understood.
Methods: Right carotid artery separation under sevoflurane and chronic social defeat stress (CSDS) in adult mice were used to establish surgical anesthesia and chronic depression models. Cognitive function was assessed by the Y maze and novel object recognition tests. A chemogenetic approach was used to modulate the locus coeruleus-dorsal hippocampal CA1 (LC-dCA1) circuit. Hippocampal synaptic alterations were evaluated by Golgi staining and whole-cell patch clamp recording.
Results: We found that CSDS induced synaptic impairments in dorsal hippocampal CA1 pyramidal neurons and cognitive deficits in adult mice after surgery under sevoflurane. Chemogenetic activation of the LC-dCA1 pathway significantly alleviated the CSDS-induced synaptic impairments and cognitive dysfunction. On the contrary, inhibition of this pathway could mimic CSDS-induced deficits. Furthermore, we showed that dopamine played an important role in CSDS-induced PNDs in adult mice after surgery/sevoflurane.
Conclusion: Overall, our results have demonstrated a vital role for the LC-dCA1 pathway in CSDS-induced PNDs in adult mice undergoing surgery with sevoflurane anesthesia.
(© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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