Anesthetic Isoflurane Increases Phosphorylated Tau Levels Mediated by Caspase Activation and Aβ Generation
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{"title"=>"Anesthetic isoflurane increases phosphorylated tau levels mediated by caspase activation and Aβ generation", "type"=>"journal", "authors"=>[{"first_name"=>"Yuanlin", "last_name"=>"Dong", "scopus_author_id"=>"13609676000"}, {"first_name"=>"Xu", "last_name"=>"Wu", "scopus_author_id"=>"7407058901"}, {"first_name"=>"Zhipeng", "last_name"=>"Xu", "scopus_author_id"=>"22939825400"}, {"first_name"=>"Yiying", "last_name"=>"Zhang", "scopus_author_id"=>"36697330500"}, {"first_name"=>"Zhongcong", "last_name"=>"Xie", "scopus_author_id"=>"8956813600"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"365066134", "pmid"=>"22745746", "doi"=>"10.1371/journal.pone.0039386", "scopus"=>"2-s2.0-84862662873", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "sgr"=>"84862662873"}, "id"=>"68e36d6c-0bab-39d2-8ff1-eb34db45ba15", "abstract"=>"Anesthetic isoflurane has been shown to promote Alzheimer's disease (AD) neuropathogenesis by inducing caspase activation and accumulation of β-amyloid (Aβ). Phosphorylation of tau protein is another important feature of AD neuropathogenesis. However, the effects of isoflurane on phosphorylated tau levels remain largely to be determined. We therefore set out to determine whether isoflurane can increase phosphorylated tau levels. 5 to 8 month-old wild-type and AD transgenic mice [B6.Cg-Tg (APPswe, PSEN1dE9)85Dbo/J] were treated with 1.4% isoflurane for two hours. The mice brain tissues were harvested at six, 12 and 24 hours after the anesthesia. For the in vitro studies, primary neurons from wild-type and the AD transgenic mice were exposed to 2% isoflurane for six hours, and were harvested at the end of anesthesia. The harvested brain tissues and neurons were subjected to Western blot analysis by which the levels of phosphorylated tau protein at Serine 262 (Tau-PS262) were determined. Here we show that the isoflurane anesthesia increased Tau-PS262 levels in brain tissues and primary neurons from the wild-type and AD transgenic mice. Moreover, the isoflurane anesthesia may induce a greater increase in Tau-PS262 levels in primary neurons and brain tissues from the AD transgenic mice. Finally, caspase activation inhibitor Z-VAD and Aβ generation inhibitor L-685,458 attenuated the isoflurane-induced increases in Tau-PS262 levels. In conclusion, clinically relevant isoflurane anesthesia increases phosphorylated tau levels, which may result from the isoflurane-induced caspase activation and Aβ generation. These findings will promote more studies to determine the effects of anesthetics on tau phosphorylation.", "link"=>"http://www.mendeley.com/research/anesthetic-isoflurane-increases-phosphorylated-tau-levels-mediated-caspase-activation-a%CE%B2-generation", "reader_count"=>31, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>9, "Neuroscience"=>3, "Physics and Astronomy"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Neuroscience"=>{"Neuroscience"=>3}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Belgium"=>1, "France"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/621483"], "description"=>"<p>Isoflurane anesthesia (lanes 2, 4 and 6) does not increase PS262 levels as compared to the control condition (lanes 1, 3 and 5) in the brain tissues of WT mice at six hours after the isoflurane anesthesia. <i>b.</i> Quantification of the Western blot shows that isoflurane anesthesia (black bar, P = 0.782, N.S.) does not increase PS262 levels as compared to the control condition (white bar). <i>c.</i> Isoflurane anesthesia (lanes 4 to 6) increases Tau-PS262 levels as compared to the control condition (lanes 1 to 3) in the brain tissues of WT mice at 12 hours after the isoflurane anesthesia. <i>d.</i> Quantification of the Western blot shows that isoflurane anesthesia (black bar, *P = 0.049) increases Tau-PS262 levels as compared to the control condition (white bar). <i>e.</i> Isoflurane anesthesia (lanes 2, 4 and 6) increases Tau-PS262 levels as compared to the control condition (lanes 1, 3 and 5) in the brain tissues of WT mice at 24 hours after the isoflurane anesthesia. <i>f.</i> Quantification of the Western blot shows that isoflurane anesthesia (black bar, *P = 0.019) increases Tau-PS262 levels as compared to the control condition (white bar). <i>g.</i> Isoflurane anesthesia (lanes 4–6 and lanes 10–12) does not increase levels of total tau as compared to the control condition (lanes 1–3 and lanes 7–9) in the brain tissues of WT mice at 12 and 24 hours after the isoflurane anesthesia. <i>h.</i> Isoflurane anesthesia (lane 5) leads to a more visible band in the Western blot analysis (at about 55 kDa) as compared to control condition (lane 4) in WT mice brain tissues, whereas tau knockout (KO) mice brain tissues (lanes 2 and 3, the negative controls) do not show such band. We have averaged results from three to six independent experiments. WT, wild-type. N = 3–6.</p>", "links"=>[], "tags"=>["increases", "tau-ps262", "levels", "tissues", "wt"], "article_id"=>291970, "categories"=>["Genetics", "Neuroscience", "Biochemistry", "Developmental Biology", "Immunology"], "users"=>["Yuanlin Dong", "Xu Wu", "Zhipeng Xu", "Yiying Zhang", "Zhongcong Xie"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039386.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Isoflurane_increases_Tau_PS262_levels_in_brain_tissues_of_WT_mice_/291970", "title"=>"Isoflurane increases Tau-PS262 levels in brain tissues of WT mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 03:40:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/621644"], "description"=>"<p><i>a.</i> Isoflurane anesthesia (lanes 2 and 4) increases Tau-PS262 levels as compared to the control condition (lanes 1 and 3) in the brain tissues of AD Tg mice at six hours after the isoflurane anesthesia. <i>b.</i> Quantification of the Western blot shows that isoflurane anesthesia (black bar, **P = 0.0069) increases Tau-PS262 levels as compared to the control condition (white bar). <i>c.</i> Isoflurane anesthesia (lanes 2 and 4) increases Tau-PS262 levels as compared to the control condition (lanes 1 and 3) in brain tissues of AD Tg mice at 12 hours after the isoflurane anesthesia. <i>d.</i> Quantification of the Western blot shows that isoflurane anesthesia (black bar, **P = 0.0016) increases Tau-PS262 levels as compared to the control condition (white bar). <i>e.</i> Isoflurane anesthesia (lanes 2, 4 and 6) increases Tau-PS262 levels as compared to the control condition (lanes 1, 3 and 5) in brain tissues of AD Tg mice at 24 hours after the isoflurane anesthesia. <i>f.</i> Quantification of the Western blot shows that isoflurane anesthesia (black bar, *P = 0.044) increases Tau-PS262 levels as compared to the control condition (white bar). We have averaged results from three independent experiments. AD, Alzheimer’s disease, Tg, transgenic. N = 3.</p>", "links"=>[], "tags"=>["increases", "tau-ps262", "levels", "tissues", "tg"], "article_id"=>292131, "categories"=>["Genetics", "Neuroscience", "Biochemistry", "Developmental Biology", "Immunology"], "users"=>["Yuanlin Dong", "Xu Wu", "Zhipeng Xu", "Yiying Zhang", "Zhongcong Xie"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039386.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Isoflurane_increases_Tau_PS262_levels_in_brain_tissues_of_AD_Tg_mice_/292131", "title"=>"Isoflurane increases Tau-PS262 levels in brain tissues of AD Tg mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 03:41:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/621807"], "description"=>"<p><i>a.</i> Isoflurane treatment (lanes 4 and 5) increases Tau-PS262 levels as compared to the control condition (lanes 1 to 3) in WT mice primary neurons. <i>b.</i> Quantification of the Western blot shows that isoflurane treatment (black bar, *P = 0.0162) increases Tau-PS262 levels as compared to the control condition (white bar). <i>c.</i> Isoflurane treatment (lane 4) increases Tau-PS262 levels as compared to the control condition (lanes 1 to 3) in AD Tg mice primary neurons. <i>d.</i> Quantification of the Western blot shows that isoflurane treatment (black bar, *P = 0.014) increases Tau-PS262 levels as compared to the control condition (white bar) in AD Tg mice primary neurons. <i>e.</i> The baseline levels of Tau-PS262 levels in AD Tg mice primary neurons (lanes 7 to 9) are higher than those in WT mice primary neurons (lanes 1 to 3); and isoflurane treatment (lanes 10 to 12) induces a greater increase in Tau-PS262 levels in AD Tg mice primary neurons than in WT mice primary neurons (lanes 4 to 6). <i>f.</i> Quantification of the Western blot shows that there is a higher baseline Tau-PS262 levels in AD Tg mice primary neurons (gray bar) than WT mice primary neurons (white bar): **P = 0.0014; and isoflurane induces a greater increase in Tau-PS262 levels in AD Tg mice primary neurons (net bar) than in WT mice primary neurons (black bar): **P = 0.0038. We have averaged results from 6 to 12 independent experiments. WT, wild-type, AD, Alzheimer’s disease, Tg, transgenic. N = 6–12.</p>", "links"=>[], "tags"=>["increases", "tau-ps262", "levels", "wt", "tg", "mice"], "article_id"=>292292, "categories"=>["Genetics", "Neuroscience", "Biochemistry", "Developmental Biology", "Immunology"], "users"=>["Yuanlin Dong", "Xu Wu", "Zhipeng Xu", "Yiying Zhang", "Zhongcong Xie"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039386.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Isoflurane_increases_Tau_PS262_levels_in_WT_and_AD_Tg_mice_primary_neurons_/292292", "title"=>"Isoflurane increases Tau-PS262 levels in WT and AD Tg mice primary neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 03:42:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/621966"], "description"=>"<p><i>a.</i> Treatment with isoflurane plus Z-VAD (lanes 6 to 9) leads to reductions in Tau-PS262 levels as compared to treatment with isoflurane plus DMSO (lanes 1 to 5) in WT mice primary neurons. <i>b.</i> Quantification of the Western blot shows that treatment with isoflurane plus Z-VAD (black bar, **P = 0.0057) leads to a reduction in Tau-PS262 levels as compared to isoflurane plus DMSO (white bar). <i>c.</i> Treatment with isoflurane plus L-685,458 (lanes 4 to 6) leads to reductions in Tau-PS262 levels as compared to treatment with isoflurane plus DMSO (lanes 1 to 3) in WT mice primary neurons. <i>d.</i> Quantification of the Western blot shows that treatment with isoflurane plus L-685,458 (black bar, *P = 0.0209) leads to reductions in Tau-PS262 levels as compared to isoflurane plus DMSO (white bar). <i>e.</i> Z-VAD (lanes 4 to 6) alone does not significantly affect Tau-PS262 levels as compared to DMSO (lanes 1 to 3) in WT mice primary neurons. <i>f.</i> Quantification of the Western blot shows that Z-VAD (black bar, P = 0.16, N.S.) does not significantly alter Tau-PS262 levels as compared to DMSO (white bar) in WT mice primary neurons. <i>g.</i> L-685,458 (lanes 4 to 6) alone does not significantly affect Tau-PS262 levels as compared to DMSO (lanes 1 to 3) in WT mice primary neurons. <i>h.</i> Quantification of the Western blot shows that L-685,458 (black bar, P = 0.219, N.S.) does not significantly alter Tau-PS262 levels as compared to DMSO (white bar) in WT mice primary neurons. We have averaged the results from 6 to 12 independent experiments. WT, wild-type; Z-VAD, Cardobenzoxy-valyl-alanyl-aspartyl-(O-methyl)-fluoromethylketone; DMSO, Dimethyl sulfoxide. N = 6−12.</p>", "links"=>[], "tags"=>["attenuate", "isoflurane-induced", "tau-ps262", "levels", "wt", "mice"], "article_id"=>292452, "categories"=>["Genetics", "Neuroscience", "Biochemistry", "Developmental Biology", "Immunology"], "users"=>["Yuanlin Dong", "Xu Wu", "Zhipeng Xu", "Yiying Zhang", "Zhongcong Xie"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039386.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Z_VAD_and_L_685_458_attenuate_the_isoflurane_induced_increase_in_Tau_PS262_levels_in_WT_mice_primary_neurons_/292452", "title"=>"Z-VAD and L-685,458 attenuate the isoflurane-induced increase in Tau-PS262 levels in WT mice primary neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 03:43:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/622089"], "description"=>"<p><i>a.</i> Treatment with isoflurane plus Z-VAD (lanes 4 to 6) leads to reductions in Tau-PS262 levels as compared to treatment with isoflurane plus DMSO (lanes 1 to 3) in AD Tg mice primary neurons. <i>b.</i> Quantification of the Western blot shows that treatment with isoflurane plus Z-VAD (black bar, **P = 0.0056) leads to reductions in Tau-PS262 levels as compared to isoflurane plus DMSO (white bar). <i>c.</i> Treatment with isoflurane plus L-685,458 (lanes 4 to 6) leads to reductions in Tau-PS262 levels as compared to treatment with isoflurane plus DMSO (lanes 1 to 3) in AD Tg mice primary neurons. <i>d.</i> Quantification of the Western blot shows that treatment with isoflurane plus L-685,458 (black bar, *P = 0.0254) leads to reductions in Tau-PS262 levels as compared to isoflurane plus DMSO (white bar). <i>e.</i> Z-VAD (lanes 4 to 6) alone does not significantly affect Tau-PS262 levels as compared to DMSO (lanes 1 to 3) in AD Tg mice primary neurons. <i>f.</i> Quantification of the Western blot shows that Z-VAD (black bar, P = 0.92, N.S.) does not significantly alter Tau-PS262 levels as compared to DMSO (white bar) in AD Tg mice primary neurons. <i>g.</i> L-685,458 (lanes 4 to 6) alone does not significantly affect Tau-PS262 levels as compared to DMSO (lanes 1 to 3) in AD Tg mice primary neurons. <i>h.</i> Quantification of the Western blot shows that L-685,458 (black bar, P = 0.78, N.S.) does not significantly alter Tau-PS262 levels as compared to DMSO (white bar) in AD Tg mice primary neurons. We have averaged the results from 6 to 12 independent experiments. AD, Alzheimer’s disease; Tg, transgenic; Z-VAD, Cardobenzoxy-valyl-alanyl-aspartyl-(O-methyl)-fluoromethylketone; DMSO, dimethyl sulfoxide. N = 6−12.</p>", "links"=>[], "tags"=>["attenuate", "isoflurane-induced", "tau-ps262", "levels", "tg", "mice"], "article_id"=>292574, "categories"=>["Genetics", "Neuroscience", "Biochemistry", "Developmental Biology", "Immunology"], "users"=>["Yuanlin Dong", "Xu Wu", "Zhipeng Xu", "Yiying Zhang", "Zhongcong Xie"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039386.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Z_VAD_and_L_685_458_attenuate_the_isoflurane_induced_increase_in_Tau_PS262_levels_in_AD_Tg_mice_primary_neurons_/292574", "title"=>"Z-VAD and L-685,458 attenuate the isoflurane-induced increase in Tau-PS262 levels in AD Tg mice primary neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 03:44:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/622202"], "description"=>"<p>Extracellular Aβ42 levels are higher in the primary neurons from AD Tg mice than those in the primary neurons from WT mice. N = 6.</p><p>Aβ, β-amyloid protein; WT, wild-type; AD, Alzheimer’s disease; Tg, transgenic.</p>", "links"=>[], "tags"=>["levels", "neurons", "wt", "tg"], "article_id"=>292692, "categories"=>["Genetics", "Neuroscience", "Biochemistry", "Developmental Biology", "Immunology"], "users"=>["Yuanlin Dong", "Xu Wu", "Zhipeng Xu", "Yiying Zhang", "Zhongcong Xie"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039386.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_946_42_levels_in_the_primary_neurons_from_WT_and_AD_Tg_mice_/292692", "title"=>"Aβ42 levels in the primary neurons from WT and AD Tg mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 03:44:52"}

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Relative Metric

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