Dynamic 5-HT2C Receptor Editing in a Mouse Model of Obesity
Publication Date
March 20, 2012
Journal
PLOS ONE
Authors
Harriët Schellekens, Gerard Clarke, Ian B. Jeffery, Timothy G. Dinan, et al
Volume
7
Issue
3
Pages
e32266
DOI
https://dx.plos.org/10.1371/journal.pone.0032266
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0032266
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22448217
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308946
Europe PMC
http://europepmc.org/abstract/MED/22448217
Web of Science
000303855700007
Scopus
84858629937
Mendeley
http://www.mendeley.com/research/dynamic-5ht-2c-receptor-editing-mouse-model-obesity
Events
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Mendeley | Further Information

{"title"=>"Dynamic 5-HT 2c receptor editing in a mouse model of obesity", "type"=>"journal", "authors"=>[{"first_name"=>"Harriët", "last_name"=>"Schellekens"}, {"first_name"=>"Gerard", "last_name"=>"Clarke"}, {"first_name"=>"Ian B.", "last_name"=>"Jeffery"}, {"first_name"=>"Timothy G.", "last_name"=>"Dinan"}, {"first_name"=>"John F.", "last_name"=>"Cryan"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0032266", "pmid"=>"22448217", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"5ecd0e86-5f1f-3465-bf40-cc3d746e2799", "abstract"=>"The central serotonergic signalling system has been shown to play an important role in appetite control and the regulation of food intake. Serotonin exerts its anorectic effects mainly through the 5-HT(1B), 5-HT(2C) and 5-HT(6) receptors and these are therefore receiving increasing attention as principal pharmacotherapeutic targets for the treatment of obesity. The 5-HT(2C) receptor has the distinctive ability to be modified by posttranscriptional RNA editing on 5 nucleotide positions (A, B, C, D, E), having an overall decreased receptor function. Recently, it has been shown that feeding behaviour and fat mass are altered when the 5-HT(2C) receptor RNA is fully edited, suggesting a potential role for 5-HT(2C) editing in obesity. The present studies investigate the expression of serotonin receptors involved in central regulation of food intake, appetite and energy expenditure, with particular focus on the level of 5-HT(2C) receptor editing. Using a leptin-deficient mouse model of obesity (ob/ob), we show increased hypothalamic 5-HT(1A) receptor expression as well as increased hippocampal 5-HT(1A), 5-HT(1B), and 5-HT(6) receptor mRNA expression in obese mice compared to lean control mice. An increase in full-length 5-HT(2C) expression, depending on time of day, as well as differences in 5-HT(2C) receptor editing were found, independent of changes in total 5-HT(2C) receptor mRNA expression. This suggests that a dynamic regulation exists of the appetite-suppressing effects of the 5-HT(2C) receptor in both the hypothalamus and the hippocampus in the ob/ob mice model of obesity. The differential 5-HT(1A), 5-HT(1B) and 5-HT(6) receptor expression and altered 5-HT(2C) receptor editing profile reported here is poised to have important consequences for the development of novel anti-obesity therapies.", "link"=>"http://www.mendeley.com/research/dynamic-5ht-2c-receptor-editing-mouse-model-obesity", "reader_count"=>21, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>3, "Student > Master"=>6}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>3, "Student > Master"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>13, "Medicine and Dentistry"=>2, "Neuroscience"=>1, "Psychology"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/664583"], "description"=>"<p>Decreased serotonin turnover is observed in hippocampus and hypothalamus of <i>ob/ob</i> mice compared to control. Unpaired, two-tailed T-test; statistical significance is notated as *** p<0.001, ** p<0.01 compared to lean control; n = 8 for hypothalamus, n = 10 for hippocampus.</p>", "links"=>[], "tags"=>["neuroscience", "neurological disorders", "Biochemistry"], "article_id"=>335067, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Harriët Schellekens", "Gerard Clarke", "Ian B. Jeffery", "Timothy G. Dinan", "John F. Cryan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032266.g003", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Monoamine_analysis_in_brain_regions_/335067", "title"=>"Monoamine analysis in brain regions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:28:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/664521"], "description"=>"<p>A) Repeated measures ANOVA showed significant increase in body weight in <i>ob/ob</i> mice; F(1;14) = 66.421;p<0.001. B) Food intake was significantly higher in <i>ob/ob</i> mice compared to lean control as analysed using repeated measures ANOVA; F(1;2) = 52.333;p<0.001; n = 8 per genotype.</p>", "links"=>[], "tags"=>["intake"], "article_id"=>335012, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Harriët Schellekens", "Gerard Clarke", "Ian B. Jeffery", "Timothy G. Dinan", "John F. Cryan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032266.g002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Body_weight_and_food_intake_in_mouse_model_of_obesity_/335012", "title"=>"Body weight and food intake in mouse model of obesity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:27:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/664688"], "description"=>"<p>A) 5-HT<sub>1A</sub> mRNA is increased in <i>ob/ob</i> mice in hippocampus and hypothalamus. B) 5-HT<sub>1B</sub> mRNA is increased in <i>ob/ob</i> mice in hippocampus. C) 5-HT<sub>6</sub> mRNA is increased in <i>ob/ob</i> mice in hippocampus. D) No change in mRNA levels of total 5-HT<sub>2C</sub> mRNA measured using qRT-PCR relative to β-actin expression. Fold changes depicted compared to hippocampus in control group. Unpaired, two-tailed T-test; statistical significance is notated as *** p<0.001, ** p<0.01, * p<0.05 compared to lean control; n = 7–8 per genotype.</p>", "links"=>[], "tags"=>["serotonin", "receptor", "mrna"], "article_id"=>335177, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Harriët Schellekens", "Gerard Clarke", "Ian B. Jeffery", "Timothy G. Dinan", "John F. Cryan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032266.g004", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Central_serotonin_5_HT_receptor_mRNA_expression_/335177", "title"=>"Central serotonin (5-HT) receptor mRNA expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:28:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/664441"], "description"=>"<p>A) The human full-length 5-HT<sub>2C</sub> gene, located on the X chromosome and processed from mRNA encoded from exon 3 to exon 6 after splicing out intronic sequence is depicted (not including 3′- or 5′- untranslated regions and not according to scale). B) The 5-HT<sub>2C</sub> gene is translated into a seven-transmembrane G-protein coupled receptor. The editing cassette is located in the second intracellular loop. C) The nucleotide sequence of the 5-HT<sub>2C</sub> editing cassette is depicted including the five nucleotide positions prone to adenosine to inosine editing.</p>", "links"=>[], "tags"=>["2c", "receptor"], "article_id"=>334924, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Harriët Schellekens", "Gerard Clarke", "Ian B. Jeffery", "Timothy G. Dinan", "John F. Cryan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032266.g001", "stats"=>{"downloads"=>4, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serotonin_2C_receptor_gene_structure_/334924", "title"=>"Serotonin 2C receptor gene structure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:27:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/664792"], "description"=>"<p>A) Significantly increased expression of the full-length 5-HT<sub>2C</sub> receptor in hypothalamus of <i>ob/ob</i> mice was observed in daytime. B) No change in expression of the full-length 5-HT<sub>2C</sub> receptor was observed in animals culled in nighttime. mRNA measured using qRT-PCR relative to β-actin expression. Unpaired, two-tailed T-test; statistical significance is notated as ** p<0.01, compared to lean control; n = 7–10 per genotype.</p>", "links"=>[], "tags"=>["nighttime", "full-length", "receptor", "mrna"], "article_id"=>335277, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Harriët Schellekens", "Gerard Clarke", "Ian B. Jeffery", "Timothy G. Dinan", "John F. Cryan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032266.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Daytime_and_nighttime_full_length_5_HT_2C_receptor_mRNA_expression_in_the_hypothalamus_/335277", "title"=>"Daytime and nighttime full-length 5-HT<sub>2C</sub> receptor mRNA expression in the hypothalamus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:29:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/665307"], "description"=>"<p>Major mouse hypothalamic 5-HT<sub>2C</sub> mRNA isoforms analysed using pyrosequencing.</p>", "links"=>[], "tags"=>["hypothalamic", "mrna", "isoforms", "analysed"], "article_id"=>335791, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Harriët Schellekens", "Gerard Clarke", "Ian B. Jeffery", "Timothy G. Dinan", "John F. Cryan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032266.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Major_mouse_hypothalamic_5_HT_2C_mRNA_isoforms_analysed_using_pyrosequencing_/335791", "title"=>"Major mouse hypothalamic 5-HT<sub>2C</sub> mRNA isoforms analysed using pyrosequencing.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 07:31:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/664887"], "description"=>"<p>Expression of 5-HT<sub>2C</sub> receptor isoforms in order of fully unedited isoform to fully edited 5-HT<sub>2C</sub> receptor isoform. A) Decreased expression of the unedited 5-HT<sub>2C</sub>-INI isoform in hippocampus of <i>ob/ob</i> mice, but not statistically significant. B) Significantly increased expression of the edited 5-HT<sub>2C</sub>-VNV (ABD edited) isoform in hippocampus of <i>ob/ob</i> mice. C) No change in mRNA levels of 5-HT<sub>2C</sub>-VSV (ABCD edited) isoform. D) No change in mRNA levels of the 5-HT<sub>2C</sub>-VGV (ABECD edited) isoform. All mRNA measured using qRT-PCR relative to β-actin expression and depicted as fold change compared to lean control littermates. Unpaired, two-tailed T-test; statistical significance is notated as ** p<0.01, compared to lean control; n = 7–8 per genotype.</p>", "links"=>[], "tags"=>["receptor", "editing"], "article_id"=>335376, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Harriët Schellekens", "Gerard Clarke", "Ian B. Jeffery", "Timothy G. Dinan", "John F. Cryan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032266.g006", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_5_HT_2C_receptor_editing_in_the_hippocampus_/335376", "title"=>"5-HT<sub>2C</sub> receptor editing in the hippocampus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:29:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/665150"], "description"=>"<p>Expression of 5-HT<sub>2C</sub> receptor isoforms in order of fully unedited isoform to fully edited 5-HT<sub>2C</sub> receptor isoform. A) No change in expression of the unedited 5-HT<sub>2C</sub>-INI isoform. B) Significantly increased expression of the edited 5-HT<sub>2C</sub>-VNI (AB edited) isoform in hypothalamus of <i>ob/ob</i> mice. C) Significantly increased expression of the edited 5-HT<sub>2C</sub>-VNV (ABD edited) isoform in hypothalamus of <i>ob/ob</i> mice. D) Significant increase in expression of mRNA levels of 5-HT<sub>2C</sub>-VSV (ABCD edited) in <i>ob/ob</i> mice compared to control. E) Significant increase in expression of mRNA levels of 5-HT<sub>2C</sub>-VGV (ABECD edited) isoform. All mRNA measured using qRT-PCR relative to β-actin expression and depicted as fold change compared to lean control littermates. Unpaired, two-tailed T-test; statistical significance is notated as ** p<0.01, * p<0.05 compared to lean control; n = 7–8 per genotype.</p>", "links"=>[], "tags"=>["receptor", "editing"], "article_id"=>335637, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Harriët Schellekens", "Gerard Clarke", "Ian B. Jeffery", "Timothy G. Dinan", "John F. Cryan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032266.g008", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_5_HT_2C_receptor_editing_in_the_hypothalamus_/335637", "title"=>"5-HT<sub>2C</sub> receptor editing in the hypothalamus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:31:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/665341"], "description"=>"<p>Site-specific hypothalamic 5-HT<sub>2C</sub> mRNA editing in <i>ob/ob</i> mice compared to control.</p>", "links"=>[], "tags"=>["hypothalamic", "mrna", "editing", "mice", "compared"], "article_id"=>335832, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Harriët Schellekens", "Gerard Clarke", "Ian B. Jeffery", "Timothy G. Dinan", "John F. Cryan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032266.t002", "stats"=>{"downloads"=>9, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Site_specific_hypothalamic_5_HT_2C_mRNA_editing_in_ob_ob_mice_compared_to_control_/335832", "title"=>"Site-specific hypothalamic 5-HT<sub>2C</sub> mRNA editing in <i>ob/ob</i> mice compared to control.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 07:32:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/665012"], "description"=>"<p>Editing of hippocampal the 5-HT<sub>2C</sub> receptor was pinpointed to nucleotide position A and B using direct sequencing. A) Column scatter plot of editing frequencies on site A and B of the editing cassette. B) A typical reverse complement chromatogram trace of an <i>ob/ob</i> mouse is depicted. Specific editing positions A to E are indicated by arrows. C) A typical control chromatogram is depicted. Unpaired, two-tailed T-test; statistical significance is notated as * p<0.05, compared to lean control; n = 5 per genotype.</p>", "links"=>[], "tags"=>["receptor", "editing"], "article_id"=>335503, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Harriët Schellekens", "Gerard Clarke", "Ian B. Jeffery", "Timothy G. Dinan", "John F. Cryan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032266.g007", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_5_HT_2C_receptor_editing_in_the_hippocampus_/335503", "title"=>"5-HT<sub>2C</sub> receptor editing in the hippocampus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:30:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/665226"], "description"=>"<p>No significantly increased expression of the adenosine deaminase, ADAR1 (A) or ADAR2 (B) in the hippocampus. No significantly increased expression of the hypothalamic adenosine deaminase, ADAR1 (C) or ADAR2 (D) in hypothalamus during the day. No significantly increased expression of the hypothalamic adenosine deaminase, ADAR1 (E) at nighttime. However, ADAR2 mRNA levels at nighttime are significantly reduced in hypothalamus of <i>ob/ob</i> mice (F). All mRNA is measured using qRT-PCR relative to β-actin expression. Unpaired, two-tailed T-test; statistical significance is notated as * p<0.05 compared to lean control; n = 7–10 per genotype.</p>", "links"=>[], "tags"=>["deaminase", "mrna"], "article_id"=>335709, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Harriët Schellekens", "Gerard Clarke", "Ian B. Jeffery", "Timothy G. Dinan", "John F. Cryan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032266.g009", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Adenosine_deaminase_ADAR_mRNA_expression_/335709", "title"=>"Adenosine deaminase (ADAR) mRNA expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:31:30"}

PMC Usage Stats | Further Information

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Relative Metric

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