Testosterone attenuates sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice
Sevoflurane anaesthesia induces phosphorylation of the microtubule-associated protein tau and cognitive impairment in neonatal, but not adult, mice. The underlying mechanisms remain largely to be determined. Sex hormones can be neuroprotective, but little is known about the influence of testosterone...
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| Veröffentlicht in: | British journal of anaesthesia : BJA 2021-12, Vol.127 (6), p.929-941 |
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| container_title | British journal of anaesthesia : BJA |
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| creator | Yang, Yongyan Liang, Feng Gao, Jie Dong, Yuanlin Zhang, Yiying Yang, Guang Soriano, Sulpicio G. Feng, Hua-Jun Xie, Zhongcong |
| description | Sevoflurane anaesthesia induces phosphorylation of the microtubule-associated protein tau and cognitive impairment in neonatal, but not adult, mice. The underlying mechanisms remain largely to be determined. Sex hormones can be neuroprotective, but little is known about the influence of testosterone on age-dependent anaesthesia effects.
Six- and 60-day-old male mice received anaesthesia with sevoflurane 3% for 2 h daily for 3 days. Morris water maze, immunoassay, immunoblotting, co-immunoprecipitation, nanobeam technology, and electrophysiology were used to assess cognition; testosterone concentrations; tau phosphorylation; glycogen synthase kinase-3β (GSK3β) activation; binding or interaction between tau and GSK3β; and neuronal activation in mice, cells, and neurones.
Compared with 60-day-old male mice, 6-day-old male mice had lower testosterone concentrations (3.03 [0.29] vs 0.44 [0.12] ng ml−1; P |
| doi_str_mv | 10.1016/j.bja.2021.08.028 |
| format | Article |
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Six- and 60-day-old male mice received anaesthesia with sevoflurane 3% for 2 h daily for 3 days. Morris water maze, immunoassay, immunoblotting, co-immunoprecipitation, nanobeam technology, and electrophysiology were used to assess cognition; testosterone concentrations; tau phosphorylation; glycogen synthase kinase-3β (GSK3β) activation; binding or interaction between tau and GSK3β; and neuronal activation in mice, cells, and neurones.
Compared with 60-day-old male mice, 6-day-old male mice had lower testosterone concentrations (3.03 [0.29] vs 0.44 [0.12] ng ml−1; P<0.01), higher sevoflurane-induced tau phosphorylation in brain (133 [20]% vs 100 [6]% in 6-day-old mice, P<0.01; 103 [8]% vs 100 [13]% in 60-day-old mice, P=0.77), and sevoflurane-induced cognitive impairment. Testosterone treatment increased brain testosterone concentrations (1.76 [0.10] vs 0.39 [0.05] ng ml−1; P<0.01) and attenuated the sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice. Testosterone inhibited the interaction between tau and GSK3β, and attenuated sevoflurane-induced inhibition of excitatory postsynaptic currents in hippocampal neurones.
Lower brain testosterone concentrations in neonatal compared with adult male mice contributed to age-dependent tau phosphorylation and cognitive impairment after sevoflurane anaesthesia. Testosterone might attenuate the sevoflurane-induced tau phosphorylation and cognitive impairment by inhibiting the interaction between tau and GSK3β.</description><identifier>ISSN: 0007-0912</identifier><identifier>EISSN: 1471-6771</identifier><identifier>DOI: 10.1016/j.bja.2021.08.028</identifier><identifier>PMID: 34686310</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anesthetics, Inhalation - administration & dosage ; Animals ; Animals, Newborn ; Cognitive Dysfunction - blood ; Cognitive Dysfunction - chemically induced ; cognitive impairment ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; neuroprotection ; Neuroscience and Neuroanaesthesia ; Phosphorylation ; sevoflurane ; Sevoflurane - administration & dosage ; sex differences ; Signal Transduction ; tau phosphorylation ; tau Proteins - drug effects ; testosterone ; Testosterone - administration & dosage ; Testosterone - blood</subject><ispartof>British journal of anaesthesia : BJA, 2021-12, Vol.127 (6), p.929-941</ispartof><rights>2021 British Journal of Anaesthesia</rights><rights>Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.</rights><rights>2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved. 2021 British Journal of Anaesthesia</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-5f8411b075dfd912af3d15de625a07b95fc39ac245cfa9bf8aa0664bcc525d053</citedby><cites>FETCH-LOGICAL-c451t-5f8411b075dfd912af3d15de625a07b95fc39ac245cfa9bf8aa0664bcc525d053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34686310$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Yongyan</creatorcontrib><creatorcontrib>Liang, Feng</creatorcontrib><creatorcontrib>Gao, Jie</creatorcontrib><creatorcontrib>Dong, Yuanlin</creatorcontrib><creatorcontrib>Zhang, Yiying</creatorcontrib><creatorcontrib>Yang, Guang</creatorcontrib><creatorcontrib>Soriano, Sulpicio G.</creatorcontrib><creatorcontrib>Feng, Hua-Jun</creatorcontrib><creatorcontrib>Xie, Zhongcong</creatorcontrib><title>Testosterone attenuates sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice</title><title>British journal of anaesthesia : BJA</title><addtitle>Br J Anaesth</addtitle><description>Sevoflurane anaesthesia induces phosphorylation of the microtubule-associated protein tau and cognitive impairment in neonatal, but not adult, mice. The underlying mechanisms remain largely to be determined. Sex hormones can be neuroprotective, but little is known about the influence of testosterone on age-dependent anaesthesia effects.
Six- and 60-day-old male mice received anaesthesia with sevoflurane 3% for 2 h daily for 3 days. Morris water maze, immunoassay, immunoblotting, co-immunoprecipitation, nanobeam technology, and electrophysiology were used to assess cognition; testosterone concentrations; tau phosphorylation; glycogen synthase kinase-3β (GSK3β) activation; binding or interaction between tau and GSK3β; and neuronal activation in mice, cells, and neurones.
Compared with 60-day-old male mice, 6-day-old male mice had lower testosterone concentrations (3.03 [0.29] vs 0.44 [0.12] ng ml−1; P<0.01), higher sevoflurane-induced tau phosphorylation in brain (133 [20]% vs 100 [6]% in 6-day-old mice, P<0.01; 103 [8]% vs 100 [13]% in 60-day-old mice, P=0.77), and sevoflurane-induced cognitive impairment. Testosterone treatment increased brain testosterone concentrations (1.76 [0.10] vs 0.39 [0.05] ng ml−1; P<0.01) and attenuated the sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice. Testosterone inhibited the interaction between tau and GSK3β, and attenuated sevoflurane-induced inhibition of excitatory postsynaptic currents in hippocampal neurones.
Lower brain testosterone concentrations in neonatal compared with adult male mice contributed to age-dependent tau phosphorylation and cognitive impairment after sevoflurane anaesthesia. Testosterone might attenuate the sevoflurane-induced tau phosphorylation and cognitive impairment by inhibiting the interaction between tau and GSK3β.</description><subject>Anesthetics, Inhalation - administration & dosage</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Cognitive Dysfunction - blood</subject><subject>Cognitive Dysfunction - chemically induced</subject><subject>cognitive impairment</subject><subject>Disease Models, Animal</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>neuroprotection</subject><subject>Neuroscience and Neuroanaesthesia</subject><subject>Phosphorylation</subject><subject>sevoflurane</subject><subject>Sevoflurane - administration & dosage</subject><subject>sex differences</subject><subject>Signal Transduction</subject><subject>tau phosphorylation</subject><subject>tau Proteins - drug effects</subject><subject>testosterone</subject><subject>Testosterone - administration & dosage</subject><subject>Testosterone - blood</subject><issn>0007-0912</issn><issn>1471-6771</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1q3TAQhUVoSW7SPkA3RS9gdyRb_qFQKKFJC4Fu0rUYS-NEF1u6SPKFvH0VbhvaTRbDLGbOmTMfYx8E1AJE92lfT3usJUhRw1CDHM7YTrS9qLq-F2_YDgD6CkYhL9hlSnsA0ctRnbOLpu2GrhGwY_6eUg4pUwyeOOZMfsNMiSc6hnnZInqqnLebIcszbvzwGFKp-LRgdsFz9Jab8OBddkfibj2giyv5zJ3nnoLHjAtfcSG-OkPv2NsZl0Tv__Qr9uvm2_319-ru5-2P6693lWmVyJWah1aICXplZ1vy49xYoSx1UiH006hm04xoZKvMjOM0D4jQde1kjJLKgmqu2JeT72GbVrKmBIq46EN0K8YnHdDp_yfePeqHcNRj18qhaYuBOBmYGFKKNL9oBehn-HqvC3z9DF_DoAv8ovn479EXxV_aZeHzaYHK60dHUSfjyBe0LpLJ2gb3iv1vtouaJg</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Yang, Yongyan</creator><creator>Liang, Feng</creator><creator>Gao, Jie</creator><creator>Dong, Yuanlin</creator><creator>Zhang, Yiying</creator><creator>Yang, Guang</creator><creator>Soriano, Sulpicio G.</creator><creator>Feng, Hua-Jun</creator><creator>Xie, Zhongcong</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20211201</creationdate><title>Testosterone attenuates sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice</title><author>Yang, Yongyan ; Liang, Feng ; Gao, Jie ; Dong, Yuanlin ; Zhang, Yiying ; Yang, Guang ; Soriano, Sulpicio G. ; Feng, Hua-Jun ; Xie, Zhongcong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-5f8411b075dfd912af3d15de625a07b95fc39ac245cfa9bf8aa0664bcc525d053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anesthetics, Inhalation - administration & dosage</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Cognitive Dysfunction - blood</topic><topic>Cognitive Dysfunction - chemically induced</topic><topic>cognitive impairment</topic><topic>Disease Models, Animal</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>neuroprotection</topic><topic>Neuroscience and Neuroanaesthesia</topic><topic>Phosphorylation</topic><topic>sevoflurane</topic><topic>Sevoflurane - administration & dosage</topic><topic>sex differences</topic><topic>Signal Transduction</topic><topic>tau phosphorylation</topic><topic>tau Proteins - drug effects</topic><topic>testosterone</topic><topic>Testosterone - administration & dosage</topic><topic>Testosterone - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Yongyan</creatorcontrib><creatorcontrib>Liang, Feng</creatorcontrib><creatorcontrib>Gao, Jie</creatorcontrib><creatorcontrib>Dong, Yuanlin</creatorcontrib><creatorcontrib>Zhang, Yiying</creatorcontrib><creatorcontrib>Yang, Guang</creatorcontrib><creatorcontrib>Soriano, Sulpicio G.</creatorcontrib><creatorcontrib>Feng, Hua-Jun</creatorcontrib><creatorcontrib>Xie, Zhongcong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of anaesthesia : BJA</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Yongyan</au><au>Liang, Feng</au><au>Gao, Jie</au><au>Dong, Yuanlin</au><au>Zhang, Yiying</au><au>Yang, Guang</au><au>Soriano, Sulpicio G.</au><au>Feng, Hua-Jun</au><au>Xie, Zhongcong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Testosterone attenuates sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice</atitle><jtitle>British journal of anaesthesia : BJA</jtitle><addtitle>Br J Anaesth</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>127</volume><issue>6</issue><spage>929</spage><epage>941</epage><pages>929-941</pages><issn>0007-0912</issn><eissn>1471-6771</eissn><abstract>Sevoflurane anaesthesia induces phosphorylation of the microtubule-associated protein tau and cognitive impairment in neonatal, but not adult, mice. The underlying mechanisms remain largely to be determined. Sex hormones can be neuroprotective, but little is known about the influence of testosterone on age-dependent anaesthesia effects.
Six- and 60-day-old male mice received anaesthesia with sevoflurane 3% for 2 h daily for 3 days. Morris water maze, immunoassay, immunoblotting, co-immunoprecipitation, nanobeam technology, and electrophysiology were used to assess cognition; testosterone concentrations; tau phosphorylation; glycogen synthase kinase-3β (GSK3β) activation; binding or interaction between tau and GSK3β; and neuronal activation in mice, cells, and neurones.
Compared with 60-day-old male mice, 6-day-old male mice had lower testosterone concentrations (3.03 [0.29] vs 0.44 [0.12] ng ml−1; P<0.01), higher sevoflurane-induced tau phosphorylation in brain (133 [20]% vs 100 [6]% in 6-day-old mice, P<0.01; 103 [8]% vs 100 [13]% in 60-day-old mice, P=0.77), and sevoflurane-induced cognitive impairment. Testosterone treatment increased brain testosterone concentrations (1.76 [0.10] vs 0.39 [0.05] ng ml−1; P<0.01) and attenuated the sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice. Testosterone inhibited the interaction between tau and GSK3β, and attenuated sevoflurane-induced inhibition of excitatory postsynaptic currents in hippocampal neurones.
Lower brain testosterone concentrations in neonatal compared with adult male mice contributed to age-dependent tau phosphorylation and cognitive impairment after sevoflurane anaesthesia. Testosterone might attenuate the sevoflurane-induced tau phosphorylation and cognitive impairment by inhibiting the interaction between tau and GSK3β.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34686310</pmid><doi>10.1016/j.bja.2021.08.028</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of anaesthesia : BJA, 2021-12, Vol.127 (6), p.929-941 |
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| subjects | Anesthetics, Inhalation - administration & dosage Animals Animals, Newborn Cognitive Dysfunction - blood Cognitive Dysfunction - chemically induced cognitive impairment Disease Models, Animal Male Mice Mice, Inbred C57BL neuroprotection Neuroscience and Neuroanaesthesia Phosphorylation sevoflurane Sevoflurane - administration & dosage sex differences Signal Transduction tau phosphorylation tau Proteins - drug effects testosterone Testosterone - administration & dosage Testosterone - blood |
| title | Testosterone attenuates sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice |
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