Molecular Hydrogen Reduces LPS-Induced Neuroinflammation and Promotes Recovery from Sickness Behaviour in Mice
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{"title"=>"Molecular hydrogen reduces lps-induced neuroinflammation and promotes recovery from sickness behaviour in mice", "type"=>"journal", "authors"=>[{"first_name"=>"Stefan", "last_name"=>"Spulber", "scopus_author_id"=>"6506649242"}, {"first_name"=>"Karin", "last_name"=>"Edoff", "scopus_author_id"=>"6603100784"}, {"first_name"=>"Lie", "last_name"=>"Hong", "scopus_author_id"=>"55324651600"}, {"first_name"=>"Shinkatsu", "last_name"=>"Morisawa", "scopus_author_id"=>"9941044200"}, {"first_name"=>"Sanetaka", "last_name"=>"Shirahata", "scopus_author_id"=>"7005610132"}, {"first_name"=>"Sandra", "last_name"=>"Ceccatelli", "scopus_author_id"=>"7004846740"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"365351864", "doi"=>"10.1371/journal.pone.0042078", "sgr"=>"84864475936", "scopus"=>"2-s2.0-84864475936", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"22860058"}, "id"=>"59d1b6fd-204f-3c92-9c47-0b069bff3dcc", "abstract"=>"Molecular hydrogen has been shown to have neuroprotective effects in mouse models of acute neurodegeneration. The effect was suggested to be mediated by its free-radical scavenger properties. However, it has been shown recently that molecular hydrogen alters gene expression and protein phosphorylation. The aim of this study was to test whether chronic ad libitum consumption of molecular hydrogen-enriched electrochemically reduced water (H-ERW) improves the outcome of lipopolysaccharide (LPS)-induced neuroinflammation. Seven days after the initiation of H-ERW treatment, C57Bl/6 mice received a single injection of LPS (0.33 mg/kg i.p.) or an equivalent volume of vehicle. The LPS-induced sickness behaviour was assessed 2 h after the injection, and recovery was assessed by monitoring the spontaneous locomotor activity in the homecage for 72 h after the administration of LPS. The mice were killed in the acute or recovery phase, and the expression of pro- and antiinflammatory cytokines in the hippocampus was assessed by real-time PCR. We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10). In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation. Consistently, molecular hydrogen modulates the activation and gene expression in a similar fashion in immortalized murine microglia (BV-2 cell line), suggesting that the effects observed in vivo may involve the modulation of microglial activation. Taken together, our data point to the regulation of cytokine expression being an additional critical mechanism underlying the beneficial effects of molecular hydrogen.", "link"=>"http://www.mendeley.com/research/molecular-hydrogen-reduces-lpsinduced-neuroinflammation-promotes-recovery-sickness-behaviour-mice", "reader_count"=>27, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>4, "Researcher"=>9, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>2, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>4, "Researcher"=>9, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>2, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>16, "Neuroscience"=>4, "Chemistry"=>2, "Psychology"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>4}, "Chemistry"=>{"Chemistry"=>2}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/315583", "https://ndownloader.figshare.com/files/315623", "https://ndownloader.figshare.com/files/315666"], "description"=>"<div><p>Molecular hydrogen has been shown to have neuroprotective effects in mouse models of acute neurodegeneration. The effect was suggested to be mediated by its free-radical scavenger properties. However, it has been shown recently that molecular hydrogen alters gene expression and protein phosphorylation. The aim of this study was to test whether chronic <em>ad libitum</em> consumption of molecular hydrogen-enriched electrochemically reduced water (H-ERW) improves the outcome of lipopolysaccharide (LPS)-induced neuroinflammation. Seven days after the initiation of H-ERW treatment, C57Bl/6 mice received a single injection of LPS (0.33 mg/kg i.p.) or an equivalent volume of vehicle. The LPS-induced sickness behaviour was assessed 2 h after the injection, and recovery was assessed by monitoring the spontaneous locomotor activity in the homecage for 72 h after the administration of LPS. The mice were killed in the acute or recovery phase, and the expression of pro- and antiinflammatory cytokines in the hippocampus was assessed by real-time PCR. We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10). In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation. Consistently, molecular hydrogen modulates the activation and gene expression in a similar fashion in immortalized murine microglia (BV-2 cell line), suggesting that the effects observed <em>in vivo</em> may involve the modulation of microglial activation. Taken together, our data point to the regulation of cytokine expression being an additional critical mechanism underlying the beneficial effects of molecular hydrogen.</p> </div>", "links"=>[], "tags"=>["molecular", "hydrogen", "reduces", "lps-induced", "neuroinflammation", "promotes", "sickness", "behaviour", "mice"], "article_id"=>122294, "categories"=>["Physiology", "Molecular Biology", "Neuroscience", "Microbiology", "Immunology"], "users"=>["Stefan Spulber", "Karin Edoff", "Lie Hong", "Shinkatsu Morisawa", "Sanetaka Shirahata", "Sandra Ceccatelli"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0042078.s001", "https://dx.doi.org/10.1371/journal.pone.0042078.s002", "https://dx.doi.org/10.1371/journal.pone.0042078.s003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Molecular_Hydrogen_Reduces_LPS_Induced_Neuroinflammation_and_Promotes_Recovery_from_Sickness_Behaviour_in_Mice/122294", "title"=>"Molecular Hydrogen Reduces LPS-Induced Neuroinflammation and Promotes Recovery from Sickness Behaviour in Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-07-31 00:38:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/598463"], "description"=>"<p>(A) Changes in bodyweight monitored for 2 weeks after the administration of LPS. Baseline bodyweight is calculated as average of the last 3 days preceding the administration of LPS. Mice drinking molecular hydrogen-enriched H-ERW drop slightly less than control mice, and recover faster to baseline bodyweight (N = 8 mice per group; * p<0.05, repeated measures ANOVA, followed by contrast analysis). (B) Spontaneous locomotor activity in a novel environment. The baseline activity was recorded 22 h prior to LPS and was used as reference for activity recorded 2 h after the injection of either vehicle (sham), or LPS. Note that the habituation to the testing conditions accounts for 25% decrease in locomotor activity. LPS administration decreases the locomotor activity to 25% in control mice, and to 45% in H-ERW mice (sham-control: N = 15; sham-H-ERW: N = 15; LPS-controls: N = 13; LPS-H-ERW: N = 14; * p<0.05, factorial ANOVA followed by contrast analysis). (C) Spontaneous locomotion in the homecage expressed as average number of visits per hour (see text for details) for 6 consecutive light-dark cycles (light and dark phases indicated at the bottom of the graph). The injection of LPS is marked by arrow. Arrowheads indicate the peaks in locomotor activity induced by handling for measuring bodyweight. Note that the pattern with 2 or 3 distinct peaks of activity is preserved in H-ERW mice even during the first dark phase following the LPS injection (although at lower amplitude than at baseline), and is restored earlier than in control mice. “baseline” indicates the two light-dark cycles that were used for deriving baseline values for all parameters analysed. (D) Spontaneous locomotor activity resting time in the homecage (light and dark phases are indicated at the top of the graph). Systemic administration of LPS (arrow) induces a significant decrease in spontaneous locomotion during both light and dark phases of the following circadian cycle, followed by a transient hyperactive period in control, but not in H-ERW mice. Resting time is significantly increased only during the dark phase following the LPS injection in H-ERW mice, compared to 3 consecutive phases in the control mice. Arrowheads indicate the timepoints where a significant change in spontaneous locomotion or resting time occurs in only one group (<i>i.e.</i> either LPS-control, or LPS-H-ERW). (E) Circadian distribution of locomotor activity and resting time. The circadian distribution of both activity and resting time was restored earlier in mice drinking H-ERW (* p<0.05, repeated measures ANOVA followed by contrast analysis). C, D, E–N = 8 mice per group, recorded in parallel in groups of 4 LPS-control and 4 LPS-H-ERW mice.</p>", "links"=>[], "tags"=>["molecular", "hydrogen", "sickness", "behaviour", "induced", "systemic"], "article_id"=>268946, "categories"=>["Physiology", "Molecular Biology", "Neuroscience", "Microbiology", "Immunology"], "users"=>["Stefan Spulber", "Karin Edoff", "Lie Hong", "Shinkatsu Morisawa", "Sanetaka Shirahata", "Sandra Ceccatelli"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0042078.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_molecular_hydrogen_in_drinking_water_on_sickness_behaviour_induced_by_systemic_administration_of_LPS_/268946", "title"=>"Effects of molecular hydrogen in drinking water on sickness behaviour induced by systemic administration of LPS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-31 02:29:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/598545"], "description"=>"<p>Data shown as fold change relative to sham mice. N = 4–5 samples/group and timepoint. Arrowheads indicate the groups and timepoints where significant gene expression regulation was found in only one of the LPS-treated groups compared to its respective sham. * - significantly different from control at the given timepoint; # - p = 0.07.</p>", "links"=>[], "tags"=>["lps-induced", "changes"], "article_id"=>269037, "categories"=>["Physiology", "Molecular Biology", "Neuroscience", "Microbiology", "Immunology"], "users"=>["Stefan Spulber", "Karin Edoff", "Lie Hong", "Shinkatsu Morisawa", "Sanetaka Shirahata", "Sandra Ceccatelli"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0042078.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_LPS_induced_changes_in_gene_expression_in_the_hippocampus_/269037", "title"=>"Analysis of LPS-induced changes in gene expression in the hippocampus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-31 02:30:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/598594"], "description"=>"<p>BV-2 cells were grown in DMEM supplemented with 10% FCS for 24 h after plating. The growth medium was replaced with serum free control- or H-ERW-DMEM, immediately before starting the recording. LPS was added to the growth medium after 24 h, and the cells were followed for an additional 24 h. (A) Total cell number relative to the average over the last 2 h before exposure to LPS. (B) Activation of BV-2 cells by exposure to LPS 1 µg/ml assessed by automated analysis of cell morphology (% from total cell number).</p>", "links"=>[], "tags"=>["proliferation", "activation"], "article_id"=>269087, "categories"=>["Physiology", "Molecular Biology", "Neuroscience", "Microbiology", "Immunology"], "users"=>["Stefan Spulber", "Karin Edoff", "Lie Hong", "Shinkatsu Morisawa", "Sanetaka Shirahata", "Sandra Ceccatelli"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0042078.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Longitudinal_analysis_of_proliferation_and_activation_upon_exposure_to_LPS_/269087", "title"=>"Longitudinal analysis of proliferation and activation upon exposure to LPS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-31 02:31:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/598645"], "description"=>"<p> (A) Quantification of activation. The BV-2 cells cultured in H-ERW-DMEM display a smaller proportion of activated cells and a larger proportion of resting cells after exposure to LPS for 2 h. (B) Gene expression regulation after 2 h exposure to LPS. In BV-2 cells grown in H-ERW-DMEM, the upregulation of TNF-α is higher, while HO-1 is not downregulated by LPS (* - p<0.05 two-tailed t-test).</p>", "links"=>[], "tags"=>["activation", "bv-2", "cells"], "article_id"=>269138, "categories"=>["Physiology", "Molecular Biology", "Neuroscience", "Microbiology", "Immunology"], "users"=>["Stefan Spulber", "Karin Edoff", "Lie Hong", "Shinkatsu Morisawa", "Sanetaka Shirahata", "Sandra Ceccatelli"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0042078.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_activation_and_gene_expression_profile_in_BV_2_cells_after_2_h_of_exposure_to_LPS_/269138", "title"=>"Analysis of activation and gene expression profile in BV-2 cells after 2 h of exposure to LPS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-31 02:32:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/598709"], "description"=>"<p>baseline: sham-H-ERW vs. sham-control; otherwise LPS-control or LPS-H-ERW vs. “no-regulation” hypothesis (one sample t-test versus fold-regulation = 1);</p><p>↑ - significant upregulation;</p><p>↓ - significant downregulation.</p>", "links"=>[], "tags"=>["immunology", "microbiology", "molecular biology", "physiology", "neuroscience"], "article_id"=>269205, "categories"=>["Physiology", "Molecular Biology", "Neuroscience", "Microbiology", "Immunology"], "users"=>["Stefan Spulber", "Karin Edoff", "Lie Hong", "Shinkatsu Morisawa", "Sanetaka Shirahata", "Sandra Ceccatelli"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0042078.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regulation_of_gene_expression_in_hippocampus_/269205", "title"=>"Regulation of gene expression in hippocampus.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-31 02:33:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/598739"], "description"=>"<p>All measurements performed at room temperature (22±1°C). FW – filtered water (control); H-ERW – hydrogen-enriched electrochemically reduced water; ORP – oxido-reductive potential; DH – dissolved hydrogen; ΔDH/Δt – rate of decay (assumed linear); N/A – not available because of sensitivity limits of the instrument.</p>#<p>- measured at 37°C;</p>*<p>- estimated at room temperature in an open glass bottle with minimal agitation.</p>", "links"=>[], "tags"=>["immunology", "microbiology", "molecular biology", "physiology", "neuroscience"], "article_id"=>269226, "categories"=>["Physiology", "Molecular Biology", "Neuroscience", "Microbiology", "Immunology"], "users"=>["Stefan Spulber", "Karin Edoff", "Lie Hong", "Shinkatsu Morisawa", "Sanetaka Shirahata", "Sandra Ceccatelli"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0042078.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_the_water_/269226", "title"=>"Characteristics of the water.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-31 02:33:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/598777"], "description"=>"<p>baseline: sham-H-ERW vs. sham-control; otherwise LPS-control or LPS-H-ERW vs. “no-regulation” hypothesis (one sample t-test versus fold-regulation = 1);</p><p>↑ - significant upregulation;</p><p>↓ - significant downregulation.</p>", "links"=>[], "tags"=>["bv-2"], "article_id"=>269268, "categories"=>["Physiology", "Molecular Biology", "Neuroscience", "Microbiology", "Immunology"], "users"=>["Stefan Spulber", "Karin Edoff", "Lie Hong", "Shinkatsu Morisawa", "Sanetaka Shirahata", "Sandra Ceccatelli"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0042078.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regulation_of_gene_expression_in_BV_2_cells_/269268", "title"=>"Regulation of gene expression in BV-2 cells.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-31 02:34:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/598815"], "description"=>"<p>Primers used for rtPCR.</p>", "links"=>[], "tags"=>["immunology", "microbiology", "molecular biology", "physiology", "neuroscience"], "article_id"=>269303, "categories"=>["Physiology", "Molecular Biology", "Neuroscience", "Microbiology", "Immunology"], "users"=>["Stefan Spulber", "Karin Edoff", "Lie Hong", "Shinkatsu Morisawa", "Sanetaka Shirahata", "Sandra Ceccatelli"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0042078.t004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primers_used_for_rtPCR_/269303", "title"=>"Primers used for rtPCR.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-31 02:35:03"}

PMC Usage Stats | Further Information

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Relative Metric

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