Lithium Impacts on the Amplitude and Period of the Molecular Circadian Clockwork
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{"title"=>"Lithium impacts on the amplitude and period of the molecular circadian clockwork", "type"=>"journal", "authors"=>[{"first_name"=>"Jian", "last_name"=>"Li", "scopus_author_id"=>"56924744500"}, {"first_name"=>"Wei Qun", "last_name"=>"Lu", "scopus_author_id"=>"9244758500"}, {"first_name"=>"Stephen", "last_name"=>"Beesley", "scopus_author_id"=>"36887741500"}, {"first_name"=>"Andrew S.I.", "last_name"=>"Loudon", "scopus_author_id"=>"7006745432"}, {"first_name"=>"Qing Jun", "last_name"=>"Meng", "scopus_author_id"=>"7202535421"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84863230433", "sgr"=>"84863230433", "pui"=>"364413487", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "pmid"=>"22428012", "doi"=>"10.1371/journal.pone.0033292"}, "id"=>"cbe7a57f-8826-38f0-8670-82a3e91e1091", "abstract"=>"Lithium salt has been widely used in treatment of Bipolar Disorder, a mental disturbance associated with circadian rhythm disruptions. Lithium mildly but consistently lengthens circadian period of behavioural rhythms in multiple organisms. To systematically address the impacts of lithium on circadian pacemaking and the underlying mechanisms, we measured locomotor activity in mice in vivo following chronic lithium treatment, and also tracked clock protein dynamics (PER2::Luciferase) in vitro in lithium-treated tissue slices/cells. Lithium lengthens period of both the locomotor activity rhythms, as well as the molecular oscillations in the suprachiasmatic nucleus, lung tissues and fibroblast cells. In addition, we also identified significantly elevated PER2::LUC expression and oscillation amplitude in both central and peripheral pacemakers. Elevation of PER2::LUC by lithium was not associated with changes in protein stabilities of PER2, but instead with increased transcription of Per2 gene. Although lithium and GSK3 inhibition showed opposing effects on clock period, they acted in a similar fashion to up-regulate PER2 expression and oscillation amplitude. Collectively, our data have identified a novel amplitude-enhancing effect of lithium on the PER2 protein rhythms in the central and peripheral circadian clockwork, which may involve a GSK3-mediated signalling pathway. These findings may advance our understanding of the therapeutic actions of lithium in Bipolar Disorder or other psychiatric diseases that involve circadian rhythm disruptions.", "link"=>"http://www.mendeley.com/research/lithium-impacts-amplitude-period-molecular-circadian-clockwork", "reader_count"=>88, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>3, "Researcher"=>16, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>4, "Student > Master"=>11, "Other"=>5, "Student > Bachelor"=>17, "Lecturer > Senior Lecturer"=>1, "Professor"=>6}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>3, "Researcher"=>16, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>4, "Student > Master"=>11, "Other"=>5, "Student > Bachelor"=>17, "Lecturer > Senior Lecturer"=>1, "Professor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>14, "Agricultural and Biological Sciences"=>41, "Neuroscience"=>6, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Chemistry"=>3, "Psychology"=>9, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>14}, "Neuroscience"=>{"Neuroscience"=>6}, "Chemistry"=>{"Chemistry"=>3}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>9}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>41}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>6}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Czech Republic"=>1, "United States"=>3, "United Kingdom"=>7, "Italy"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/343311", "https://ndownloader.figshare.com/files/343356", "https://ndownloader.figshare.com/files/343400"], "description"=>"<div><p>Lithium salt has been widely used in treatment of Bipolar Disorder, a mental disturbance associated with circadian rhythm disruptions. Lithium mildly but consistently lengthens circadian period of behavioural rhythms in multiple organisms. To systematically address the impacts of lithium on circadian pacemaking and the underlying mechanisms, we measured locomotor activity in mice <em>in vivo</em> following chronic lithium treatment, and also tracked clock protein dynamics (PER2::Luciferase) <em>in vitro</em> in lithium-treated tissue slices/cells. Lithium lengthens period of both the locomotor activity rhythms, as well as the molecular oscillations in the suprachiasmatic nucleus, lung tissues and fibroblast cells. In addition, we also identified significantly elevated PER2::LUC expression and oscillation amplitude in both central and peripheral pacemakers. Elevation of PER2::LUC by lithium was not associated with changes in protein stabilities of PER2, but instead with increased transcription of <em>Per2</em> gene. Although lithium and GSK3 inhibition showed opposing effects on clock period, they acted in a similar fashion to up-regulate PER2 expression and oscillation amplitude. Collectively, our data have identified a novel amplitude-enhancing effect of lithium on the PER2 protein rhythms in the central and peripheral circadian clockwork, which may involve a GSK3-mediated signalling pathway. These findings may advance our understanding of the therapeutic actions of lithium in Bipolar Disorder or other psychiatric diseases that involve circadian rhythm disruptions.</p> </div>", "links"=>[], "tags"=>["lithium", "impacts", "amplitude", "molecular", "circadian", "clockwork"], "article_id"=>127866, "categories"=>["Chemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Jian Li", "Wei-qun Lu", "Stephen Beesley", "Andrew S. I. Loudon", "Qing-Jun Meng"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0033292.s001", "https://dx.doi.org/10.1371/journal.pone.0033292.s002", "https://dx.doi.org/10.1371/journal.pone.0033292.s003"], "stats"=>{"downloads"=>3, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Lithium_Impacts_on_the_Amplitude_and_Period_of_the_Molecular_Circadian_Clockwork/127866", "title"=>"Lithium Impacts on the Amplitude and Period of the Molecular Circadian Clockwork", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-03-12 02:11:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/669387"], "description"=>"<p>A,B, Representative traces of PMT recording (A) and period analysis (B) for <i>Bmal1::luc</i> stable Rat1 cells treated with lithium. Mean ± SD; *, p<0.05 vs. Control; **, p<0.01 vs. Control; n = 4 for each group. Untreated group was used as control.</p>", "links"=>[], "tags"=>["lengthens", "oscillation", "rat1"], "article_id"=>339875, "categories"=>["Chemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Jian Li", "Wei-qun Lu", "Stephen Beesley", "Andrew S. I. Loudon", "Qing-Jun Meng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033292.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lithium_lengthens_period_of_Bmal1_luc_oscillation_in_Rat1_cells_/339875", "title"=>"Lithium lengthens period of <i>Bmal1::luc</i> oscillation in Rat1 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-12 02:44:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/669450"], "description"=>"<p>A, Decay of PER2::LUC bioluminescence from lung fibroblasts was monitored by PMT recording. Fibroblasts were pretreated with lithium for 48 hrs, followed by treatment with cycloheximide (CHX, 20 µg/mL). Half-lives for PER2::LUC bioluminescence were analyzed by normalizing data to the peak level of expression (time 0 after CHX) and the minimum after 8 hours, and plotted as mean ± SEM. Untreated group was used as control. B, Lung fibroblasts isolated from WT and CK1ε<sup>tau</sup> mice (on PER2::LUC background) were synchronized and subjected to PMT recording. Top panel, Raw traces; bottom panel, baseline corrected data. Black arrow indicates time of lithium treatment. C, <i>rPer2</i> mRNA level was quantified by Taqman Q-PCR in Rat1 fibroblasts synchronized with 100 nM dexamethasone. 24 hours later, cells were treated with different doses of either lithium or BIO for 12 hrs before total RNA collection. Data were normalized to <i>rβ-actin</i>. To calculate a relative change the average of the 3 replicate CT values for each sample was used. Mean ± SEM *, p<0.05; **, p<0.01; n = 4 for each group. Untreated group was used as control.</p>", "links"=>[], "tags"=>["decay", "increases"], "article_id"=>339938, "categories"=>["Chemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Jian Li", "Wei-qun Lu", "Stephen Beesley", "Andrew S. I. Loudon", "Qing-Jun Meng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033292.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lithium_does_not_affect_decay_rate_of_PER2_LUC_but_instead_increases_Per2_transcription_/339938", "title"=>"Lithium does not affect decay rate of PER2::LUC, but instead increases <i>Per2</i> transcription.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-12 02:45:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/669287"], "description"=>"<p>A,B, Representative traces of PER2::LUC rhythms from lung fibroblasts treated with increasing doses of lithium (A) or the GSK3 inhibitor BIO (B). Black arrow indicates time of treatment. Untreated group was used as control for lithium; DMSO was used as control for BIO. C, Period and amplitude analysis for PER2::LUC rhythms in lung fibroblasts following treatment with either lithium (20 mM), or BIO (2 µM). Mean ± SEM; *, p<0.05 vs. Control; **, p<0.01 vs. Control; ***, p<0.001 vs. Control; n = 4 for each group. D,E, Representative raw traces (D) and baseline corrected traces (E) of PER2::LUC rhythms from lung fibroblasts treated with lithium alone (20 mM), or in combination with BIO(2 µM). DMSO was used as vehicle control for BIO. F, Amplitude analysis for data in (D) and (E). **, p<0.01 vs. vehicle; ***, p<0.001 vs. vehicle; n = 4 for each group.</p>", "links"=>[], "tags"=>["lithium", "gsk3", "inhibition", "amplitude"], "article_id"=>339772, "categories"=>["Chemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Jian Li", "Wei-qun Lu", "Stephen Beesley", "Andrew S. I. Loudon", "Qing-Jun Meng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033292.g003", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_lithium_and_GSK3_inhibition_on_PER2_LUC_expression_and_amplitude_of_oscillation_/339772", "title"=>"Effects of lithium and GSK3 inhibition on PER2::LUC expression and amplitude of oscillation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-12 02:42:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/669206"], "description"=>"<p>A,B, Representative PER2::LUC traces from ectopic lung slices (A, raw data; B, baseline correction of raw data). Black arrow indicates time of lithium treatment. Untreated group was used as control. C,D, Period and amplitude analysis. The net period changes were analyzed by normalizing to the control slices and expressed as mean ± SEM. The amplitude changes were analyzed based on the first peak after treatment in the baseline corrected data. *, p<0.05; **, p<0.01, n = 5. E, Bright field and bioluminescence imaging of lung slices. Peak and trough of oscillations were determined based on the bioluminescent intensity of the CCD camera recording. White arrowheads indicate bronchiole and blood vessel.</p>", "links"=>[], "tags"=>["lengthens", "circadian", "enhances"], "article_id"=>339690, "categories"=>["Chemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Jian Li", "Wei-qun Lu", "Stephen Beesley", "Andrew S. I. Loudon", "Qing-Jun Meng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033292.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lithium_lengthens_circadian_period_and_enhances_PER2_LUC_expression_in_lung_slices_/339690", "title"=>"Lithium lengthens circadian period and enhances PER2::LUC expression in lung slices.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-12 02:41:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/669119"], "description"=>"<p>A, Representative behavioral rhythm and period analysis for WT C57BL/6 mice. Black arrow indicates initiation of lithium treatment (10 mM in drinking water). DD, constant darkness. Data were expressed as mean ± SEM; **, p<0.01, n = 6. B, Representative traces of PER2::LUC bioluminescence oscillations and analysis of period and amplitude in organotypic SCN slices recorded by PMT photon counting. Black arrow indicates time of lithium treatment. Untreated group was used as control. Data were expressed as mean ± SEM; **, p<0.01, n = 6.</p>", "links"=>[], "tags"=>["lengthens", "rhythms", "alters", "molecular", "oscillations"], "article_id"=>339602, "categories"=>["Chemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Jian Li", "Wei-qun Lu", "Stephen Beesley", "Andrew S. I. Loudon", "Qing-Jun Meng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033292.g001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lithium_lengthens_period_for_behavioral_rhythms_and_alters_molecular_oscillations_in_the_SCN_/339602", "title"=>"Lithium lengthens period for behavioral rhythms and alters molecular oscillations in the SCN.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-12 02:40:02"}

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Relative Metric

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