Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway

Yong Xiao,1,* Lifang Zhou,2,* Youbing Tu,1 Yuantao Li,3 Yubing Liang,4 Xu Zhang,1 Jing Lv,1 Yu Zhong,1 Yubo Xie1 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, Institute of Car...

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Autores principales:	Xiao Y, Zhou L, Tu Y, Li Y, Liang Y, Zhang X, Lv J, Zhong Y, Xie Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	propofol dexmedetomidine long-term neurotoxicity PI3K hippocampus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/2ae8176a9e7a4f2f992e513e9bfafa6d
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spelling	oai:doaj.org-article:2ae8176a9e7a4f2f992e513e9bfafa6d2021-12-02T00:50:31ZDexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway1178-2021https://doaj.org/article/2ae8176a9e7a4f2f992e513e9bfafa6d2018-08-01T00:00:00Zhttps://www.dovepress.com/dexmedetomidine-attenuates-the-propofol-induced-long-term-neurotoxicit-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Yong Xiao,1,* Lifang Zhou,2,* Youbing Tu,1 Yuantao Li,3 Yubing Liang,4 Xu Zhang,1 Jing Lv,1 Yu Zhong,1 Yubo Xie1 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Anesthesiology, Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 4Department of Anesthesiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China *These authors contributed equally to this work Background: Propofol induces short- and long-term neurotoxicity. Our previous study showed that dexmedetomidine (Dex) can attenuate the propofol-induced acute neurotoxicity in rodents by enhancing the PI3K/Akt signaling. However, whether treatment of young rats with Dex could protect them from long-term neurotoxicity induced by propofol is unclear. Materials and methods: Seven-day-old male Sprague Dawley rats were randomized and injected intraperitoneally with saline (100 µL, NS), propofol (100 mg/kg), Dex (75 µg/kg), propofol (100 mg/kg) plus Dex (25, 50 or 75 µg/kg), 10% dimethyl sulfoxide (DMSO, 100 µL) or TDZD-8 (a GSK3β inhibitor, 1 mg/kg), or intracerebroventricularly with DMSO (5 µL) or LY294002 (a PI3K inhibitor, 25 µg/5 µL DMSO). Other rats in the experimental group were injected with the same doses of propofol, Dex and LY294002 or TDZD-8. All the rats were monitored until they were 9 weeks old. Their spatial learning and memory were tested by Morris water maze. The neuronal apoptosis, expression of PSD95, expression and phosphorylation of Akt and GSK3β and synaptic ultrastructures were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, immunohistochemistry, Western blot and transmission electron microscopy assays, respectively. Results: Compared with the NS control group, young rats injected with intralipid, Dex, TDZD-8, LY294002 or DMSO alone did not show any significant change as they aged. Propofol significantly increased the escape latency time, hippocampal neuroapoptosis and synaptic ultrastructural changes but decreased the relative levels of PSD95 expression, and Akt and GSK3β phosphorylation in the developing hippocampus of the rats. The neuronal toxic effects of propofol were significantly mitigated by the pretreatment with a higher dose of Dex. The neuroprotective effect of Dex was enhanced by the treatment with TDZD-8, but was completely abrogated by the treatment with LY294002. Conclusion: Our results indicated that the pretreatment of young rats with Dex attenuated the propofol-induced long-term neurotoxicity in their developing hippocampus by enhancing the PI3K/Akt signaling. Keywords: propofol, dexmedetomidine, long-term neurotoxicity, PI3K, hippocampusXiao YZhou LTu YLi YLiang YZhang XLv JZhong YXie YDove Medical Pressarticlepropofoldexmedetomidinelong-term neurotoxicityPI3KhippocampusNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 14, Pp 2191-2206 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	propofol dexmedetomidine long-term neurotoxicity PI3K hippocampus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	propofol dexmedetomidine long-term neurotoxicity PI3K hippocampus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Xiao Y Zhou L Tu Y Li Y Liang Y Zhang X Lv J Zhong Y Xie Y Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway
description	Yong Xiao,1,* Lifang Zhou,2,* Youbing Tu,1 Yuantao Li,3 Yubing Liang,4 Xu Zhang,1 Jing Lv,1 Yu Zhong,1 Yubo Xie1 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Anesthesiology, Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 4Department of Anesthesiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China *These authors contributed equally to this work Background: Propofol induces short- and long-term neurotoxicity. Our previous study showed that dexmedetomidine (Dex) can attenuate the propofol-induced acute neurotoxicity in rodents by enhancing the PI3K/Akt signaling. However, whether treatment of young rats with Dex could protect them from long-term neurotoxicity induced by propofol is unclear. Materials and methods: Seven-day-old male Sprague Dawley rats were randomized and injected intraperitoneally with saline (100 µL, NS), propofol (100 mg/kg), Dex (75 µg/kg), propofol (100 mg/kg) plus Dex (25, 50 or 75 µg/kg), 10% dimethyl sulfoxide (DMSO, 100 µL) or TDZD-8 (a GSK3β inhibitor, 1 mg/kg), or intracerebroventricularly with DMSO (5 µL) or LY294002 (a PI3K inhibitor, 25 µg/5 µL DMSO). Other rats in the experimental group were injected with the same doses of propofol, Dex and LY294002 or TDZD-8. All the rats were monitored until they were 9 weeks old. Their spatial learning and memory were tested by Morris water maze. The neuronal apoptosis, expression of PSD95, expression and phosphorylation of Akt and GSK3β and synaptic ultrastructures were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, immunohistochemistry, Western blot and transmission electron microscopy assays, respectively. Results: Compared with the NS control group, young rats injected with intralipid, Dex, TDZD-8, LY294002 or DMSO alone did not show any significant change as they aged. Propofol significantly increased the escape latency time, hippocampal neuroapoptosis and synaptic ultrastructural changes but decreased the relative levels of PSD95 expression, and Akt and GSK3β phosphorylation in the developing hippocampus of the rats. The neuronal toxic effects of propofol were significantly mitigated by the pretreatment with a higher dose of Dex. The neuroprotective effect of Dex was enhanced by the treatment with TDZD-8, but was completely abrogated by the treatment with LY294002. Conclusion: Our results indicated that the pretreatment of young rats with Dex attenuated the propofol-induced long-term neurotoxicity in their developing hippocampus by enhancing the PI3K/Akt signaling. Keywords: propofol, dexmedetomidine, long-term neurotoxicity, PI3K, hippocampus
format	article
author	Xiao Y Zhou L Tu Y Li Y Liang Y Zhang X Lv J Zhong Y Xie Y
author_facet	Xiao Y Zhou L Tu Y Li Y Liang Y Zhang X Lv J Zhong Y Xie Y
author_sort	Xiao Y
title	Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway
title_short	Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway
title_full	Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway
title_fullStr	Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway
title_full_unstemmed	Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway
title_sort	dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the pi3k/akt signaling pathway
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/2ae8176a9e7a4f2f992e513e9bfafa6d
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Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway

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