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Dexmedetomidine protects rats from postoperative cognitive dysfunction via regulating the GABAB R-mediated cAMP-PKA-CREB signaling pathway.
Neuropathology. 2019 Feb; 39(1):30-38.N

Abstract

This work attempts to discuss whether dexmedetomidine (Dex) can protect rats from postoperative cognitive dysfunction (POCD) through regulating the γ-aminobutyric acid-B receptor (GABAB R)-mediated cyclic adenosine monophosphate (cAMP) - protein kinase A (PKA) - cAMP-response element binding (cAMP-PKA-CREB) signaling pathway. Sprague-Dawley rats were divided into a non-surgical group (Control), a surgical group (Model), a surgical group treated with Dex (Model + Dex), a surgical group treated with GABAB R antagonist (Model + CGP 35348) and a surgical group treated with Dex and GABAB R agonist (Model + Dex + Baclofen). Cognitive and memory functions were evaluated by Y-maze test and open-field test. The neuronal morphology of the hippocampus was observed by hematoxylin and eosin staining and neuronal apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling method. Inflammatory factors and cAMP levels were detected by enzyme-linked immunosorbent assay while expressions of GABAB R and PKA-CREB pathway-related molecules by Western blot. Compared with control rats, the model rats exhibited reduced alternation rates with a prolonged time spent in the central zone; meanwhile, levels of tumor necrosis factor-α and interleukin-1β and the apoptotic index, as well as GABAB R1 and GABAB R2 expressions were increased in the model rats, but the cAMP-PKA-CREB pathway was inhibited (all P < 0.05). When treated with either Dex or CGP 35348, the surgical rats displayed an opposite tendency concerning the above factors as compared to the model rats (all P < 0.05). Furthermore, Baclofen, the agonist of GABAB R, could reverse the protective effect of Dex against POCD in rats. Dex protects rats from POCD possibly via suppressing GABAB R to up-regulate the cAMP-PKA-CREB signaling pathway, thereby alleviating the hippocampal inflammation caused by surgical trauma.

Authors+Show Affiliations

Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30592096

Citation

Zhu, Yun-Sheng, et al. "Dexmedetomidine Protects Rats From Postoperative Cognitive Dysfunction Via Regulating the GABAB R-mediated cAMP-PKA-CREB Signaling Pathway." Neuropathology : Official Journal of the Japanese Society of Neuropathology, vol. 39, no. 1, 2019, pp. 30-38.
Zhu YS, Xiong YF, Luo FQ, et al. Dexmedetomidine protects rats from postoperative cognitive dysfunction via regulating the GABAB R-mediated cAMP-PKA-CREB signaling pathway. Neuropathology. 2019;39(1):30-38.
Zhu, Y. S., Xiong, Y. F., Luo, F. Q., & Min, J. (2019). Dexmedetomidine protects rats from postoperative cognitive dysfunction via regulating the GABAB R-mediated cAMP-PKA-CREB signaling pathway. Neuropathology : Official Journal of the Japanese Society of Neuropathology, 39(1), 30-38. https://doi.org/10.1111/neup.12530
Zhu YS, et al. Dexmedetomidine Protects Rats From Postoperative Cognitive Dysfunction Via Regulating the GABAB R-mediated cAMP-PKA-CREB Signaling Pathway. Neuropathology. 2019;39(1):30-38. PubMed PMID: 30592096.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dexmedetomidine protects rats from postoperative cognitive dysfunction via regulating the GABAB R-mediated cAMP-PKA-CREB signaling pathway. AU - Zhu,Yun-Sheng, AU - Xiong,Ying-Fen, AU - Luo,Fo-Quan, AU - Min,Jia, Y1 - 2018/12/27/ PY - 2018/07/13/received PY - 2018/11/16/revised PY - 2018/11/16/accepted PY - 2018/12/29/pubmed PY - 2019/3/22/medline PY - 2018/12/29/entrez KW - GABABR KW - cAMP-PKA-CREB signaling pathway KW - dexmedetomidine KW - postoperative cognitive dysfunction SP - 30 EP - 38 JF - Neuropathology : official journal of the Japanese Society of Neuropathology JO - Neuropathology VL - 39 IS - 1 N2 - This work attempts to discuss whether dexmedetomidine (Dex) can protect rats from postoperative cognitive dysfunction (POCD) through regulating the γ-aminobutyric acid-B receptor (GABAB R)-mediated cyclic adenosine monophosphate (cAMP) - protein kinase A (PKA) - cAMP-response element binding (cAMP-PKA-CREB) signaling pathway. Sprague-Dawley rats were divided into a non-surgical group (Control), a surgical group (Model), a surgical group treated with Dex (Model + Dex), a surgical group treated with GABAB R antagonist (Model + CGP 35348) and a surgical group treated with Dex and GABAB R agonist (Model + Dex + Baclofen). Cognitive and memory functions were evaluated by Y-maze test and open-field test. The neuronal morphology of the hippocampus was observed by hematoxylin and eosin staining and neuronal apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling method. Inflammatory factors and cAMP levels were detected by enzyme-linked immunosorbent assay while expressions of GABAB R and PKA-CREB pathway-related molecules by Western blot. Compared with control rats, the model rats exhibited reduced alternation rates with a prolonged time spent in the central zone; meanwhile, levels of tumor necrosis factor-α and interleukin-1β and the apoptotic index, as well as GABAB R1 and GABAB R2 expressions were increased in the model rats, but the cAMP-PKA-CREB pathway was inhibited (all P < 0.05). When treated with either Dex or CGP 35348, the surgical rats displayed an opposite tendency concerning the above factors as compared to the model rats (all P < 0.05). Furthermore, Baclofen, the agonist of GABAB R, could reverse the protective effect of Dex against POCD in rats. Dex protects rats from POCD possibly via suppressing GABAB R to up-regulate the cAMP-PKA-CREB signaling pathway, thereby alleviating the hippocampal inflammation caused by surgical trauma. SN - 1440-1789 UR - https://www.unboundmedicine.com/medline/citation/30592096/Dexmedetomidine_protects_rats_from_postoperative_cognitive_dysfunction_via_regulating_the_GABAB_R_mediated_cAMP_PKA_CREB_signaling_pathway_ L2 - https://doi.org/10.1111/neup.12530 DB - PRIME DP - Unbound Medicine ER -