Peripheral Nerve Injury Is Associated with Chronic, Reversible Changes in Global DNA Methylation in the Mouse Prefrontal Cortex
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{"title"=>"Peripheral Nerve Injury Is Associated with Chronic, Reversible Changes in Global DNA Methylation in the Mouse Prefrontal Cortex", "type"=>"journal", "authors"=>[{"first_name"=>"Maral", "last_name"=>"Tajerian", "scopus_author_id"=>"37762360800"}, {"first_name"=>"Sebastian", "last_name"=>"Alvarado", "scopus_author_id"=>"51664679700"}, {"first_name"=>"Magali", "last_name"=>"Millecamps", "scopus_author_id"=>"23474291300"}, {"first_name"=>"Pascal", "last_name"=>"Vachon", "scopus_author_id"=>"35390319400"}, {"first_name"=>"Cecilia", "last_name"=>"Crosby", "scopus_author_id"=>"55595753800"}, {"first_name"=>"M. Catherine", "last_name"=>"Bushnell", "scopus_author_id"=>"7005808290"}, {"first_name"=>"Moshe", "last_name"=>"Szyf", "scopus_author_id"=>"7005418666"}, {"first_name"=>"Laura S.", "last_name"=>"Stone", "scopus_author_id"=>"7201963842"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"368226743", "sgr"=>"84873828211", "pmid"=>"23383129", "scopus"=>"2-s2.0-84873828211", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0055259", "issn"=>"19326203"}, "id"=>"cf1e3c6c-e5a0-35fb-84c4-0598b381d3e4", "abstract"=>"Changes in brain structure and cortical function are associated with many chronic pain conditions including low back pain and fibromyalgia. The magnitude of these changes correlates with the duration and/or the intensity of chronic pain. Most studies report changes in common areas involved in pain modulation, including the prefrontal cortex (PFC), and pain-related pathological changes in the PFC can be reversed with effective treatment. While the mechanisms underlying these changes are unknown, they must be dynamically regulated. Epigenetic modulation of gene expression in response to experience and environment is reversible and dynamic. Epigenetic modulation by DNA methylation is associated with abnormal behavior and pathological gene expression in the central nervous system. DNA methylation might also be involved in mediating the pathologies associated with chronic pain in the brain. We therefore tested a) whether alterations in DNA methylation are found in the brain long after chronic neuropathic pain is induced in the periphery using the spared nerve injury modal and b) whether these injury-associated changes are reversible by interventions that reverse the pathologies associated with chronic pain. Six months following peripheral nerve injury, abnormal sensory thresholds and increased anxiety were accompanied by decreased global methylation in the PFC and the amygdala but not in the visual cortex or the thalamus. Environmental enrichment attenuated nerve injury-induced hypersensitivity and reversed the changes in global PFC methylation. Furthermore, global PFC methylation correlated with mechanical and thermal sensitivity in neuropathic mice. In summary, induction of chronic pain by peripheral nerve injury is associated with epigenetic changes in the brain. These changes are detected long after the original injury, at a long distance from the site of injury and are reversible with environmental manipulation. Changes in brain structure and cortical function that are associated with chronic pain conditions may therefore be mediated by epigenetic mechanisms.", "link"=>"http://www.mendeley.com/research/peripheral-nerve-injury-associated-chronic-reversible-changes-global-dna-methylation-mouse-prefronta", "reader_count"=>68, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>21, "Student > Doctoral Student"=>9, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>3, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>11}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>21, "Student > Doctoral Student"=>9, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>3, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>11}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Engineering"=>1, "Nursing and Health Professions"=>6, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>20, "Medicine and Dentistry"=>18, "Neuroscience"=>8, "Arts and Humanities"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Sports and Recreations"=>1, "Psychology"=>4, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>18}, "Neuroscience"=>{"Neuroscience"=>8}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Psychology"=>{"Psychology"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>20}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"United States"=>1, "China"=>1, "United Kingdom"=>2, "Spain"=>1}, "group_count"=>5}

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  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/499876/Figure_1.tif"], "description"=>"<p>Nerve injured mice show a decrease in mechanical thresholds (<b>A</b>) and an increase in acetone-evoked behaviors, indicative of cold sensitivity (<b>B</b>) on the hindpaw, measured by the von Frey filament test and the acetone tests, respectively. In addition, these mice show signs of motor dysfunction, measured by the rotarod assay (<b>C</b>). In the open field assay (<b>D</b>), neuropathic mice do not differ from control mice in overall levels of spontaneous activity, measured by the number of peripheral squares covered in the open field (<b>e</b>). However, they spent less time spent in the central square of the open field, indicative of anxiety-like behavior (<b>f</b>). * = p<0.05, *** = p<0.0001, n = 10/group, error bars indicate S.E.M.</p>", "links"=>[], "tags"=>["signs", "neuropathic", "months"], "article_id"=>170388, "categories"=>["Neuroscience", "Genetics"], "users"=>["Maral Tajerian", "Sebastian Alvarado", "Magali Millecamps", "Pascal Vachon", "Cecilia Crosby", "M. Catherine Bushnell", "Moshe Szyf", "Laura S. Stone"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0055259.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Behavioral_Signs_of_Neuropathic_Pain_Six_Months_following_Nerve_Injury_/170388", "title"=>"Behavioral Signs of Neuropathic Pain Six Months following Nerve Injury.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:22:29"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/500040/Figure_2.tif"], "description"=>"<p>Nerve injured mice show a decrease in global methylation in the PFC (<b>a</b>) and amygdala (<b>b</b>) six months after the induction of peripheral neuropathy. No such changes were observed in the thalamus (<b>c</b>) or visual cortex (<b>d</b>). *** = p<0.0001, n = 8–10/group, error bars indicate S.E.M.</p>", "links"=>[], "tags"=>["methylation", "cns", "months"], "article_id"=>170551, "categories"=>["Neuroscience", "Genetics"], "users"=>["Maral Tajerian", "Sebastian Alvarado", "Magali Millecamps", "Pascal Vachon", "Cecilia Crosby", "M. Catherine Bushnell", "Moshe Szyf", "Laura S. Stone"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0055259.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Global_Methylation_in_the_CNS_Six_Months_following_Nerve_Injury_/170551", "title"=>"Global Methylation in the CNS Six Months following Nerve Injury.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:23:23"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/500222/Figure_3.tif"], "description"=>"<p>Three months following nerve injury and the establishment of chronic neuropathic pain, mice were subjected to an enriched or an impoverished environment for an additional two months. Environmental enrichment resulted in decreases in mechanical (<b>A</b>) and cold sensitivity (<b>B</b>) in nerve-injured animals towards control values. (<b>C</b>) These changes in cutaneous hypersensitivity following environmental enrichment were accompanied by reversal of the nerve injury-induced decreases in global methylation in the impoverished group such that global methylation was no longer different from control values (1-way ANOVA, F<sub>(3,21)</sub> = 4.545, p = 0.013, tukeys multiple comparison test). * = p<0.05, ** = p<0.01,*** = p<0.001; control, enriched vs. impoverished or injured, enriched vs. impoverished; n = 5–8/group, error bars indicate S.E.M.</p>", "links"=>[], "tags"=>["enrichment", "reverses", "injury-induced", "neuropathic", "pathological", "changes", "dna", "methylation", "prefrontal"], "article_id"=>170733, "categories"=>["Neuroscience", "Genetics"], "users"=>["Maral Tajerian", "Sebastian Alvarado", "Magali Millecamps", "Pascal Vachon", "Cecilia Crosby", "M. Catherine Bushnell", "Moshe Szyf", "Laura S. Stone"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0055259.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Environmental_Enrichment_Reverses_Nerve_Injury_Induced_Neuropathic_Pain_and_Pathological_Changes_in_DNA_Methylation_in_the_Prefrontal_Cortex_/170733", "title"=>"Environmental Enrichment Reverses Nerve Injury-Induced Neuropathic Pain and Pathological Changes in DNA Methylation in the Prefrontal Cortex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:24:23"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/500309/Figure_4.tif"], "description"=>"<p>Correlation analysis was performed on the data from <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055259#pone-0055259-g003\" target=\"_blank\">Figure 3</a>. Significant correlations were observed between % global methylation and hypersensitivity to mechanical (<b>a</b>) and cold stimuli (<b>b</b>), in neuropathic but not control mice. * = p<0.05, ** = p<0.01.</p>", "links"=>[], "tags"=>["methylation", "prefrontal", "cortex", "correlates", "injury-induced"], "article_id"=>170820, "categories"=>["Neuroscience", "Genetics"], "users"=>["Maral Tajerian", "Sebastian Alvarado", "Magali Millecamps", "Pascal Vachon", "Cecilia Crosby", "M. Catherine Bushnell", "Moshe Szyf", "Laura S. Stone"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0055259.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Global_Methylation_in_the_Prefrontal_Cortex_Correlates_with_the_Magnitude_of_Nerve_Injury_Induced_Hypersensitivity_/170820", "title"=>"Global Methylation in the Prefrontal Cortex Correlates with the Magnitude of Nerve Injury-Induced Hypersensitivity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:24:52"}

PMC Usage Stats | Further Information

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Relative Metric

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