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Increased stathmin1 expression in the dentate gyrus of mice causes abnormal axonal arborizations
Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in multiple brain functions. To clarify the cause of abnormal behavior in PACAP deficient-mice, we attempted the identification of genes whose expression was altered in the dentate gyrus of PACAP-deficient mice using the differen...
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| Published in: | PloS one 2010-01, Vol.5 (1), p.e8596-e8596 |
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| creator | Yamada, Kohei Matsuzaki, Shinsuke Hattori, Tsuyoshi Kuwahara, Ryusuke Taniguchi, Manabu Hashimoto, Hitoshi Shintani, Norihito Baba, Akemichi Kumamoto, Natsuko Yamada, Kazuo Yoshikawa, Takeo Katayama, Taiichi Tohyama, Masaya |
| description | Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in multiple brain functions. To clarify the cause of abnormal behavior in PACAP deficient-mice, we attempted the identification of genes whose expression was altered in the dentate gyrus of PACAP-deficient mice using the differential display method. Expression of stathmin1 was up-regulated in the dentate gyrus at both the mRNA and protein levels. PACAP stimulation inhibited stathmin1 expression in PC12 cells, while increased stathmin1expression in neurons of the subgranular zone and in primary cultured hippocampal neurons induced abnormal arborization of axons. We also investigated the pathways involved in PACAP deficiency. Ascl1 binds to E10 box of the stathmin1 promoter and increases stathmin1 expression. Inhibitory bHLH proteins (Hes1 and Id3) were rapidly up-regulated by PACAP stimulation, and Hes1 could suppress Ascl1 expression and Id3 could inhibit Ascl1 signaling. We also detected an increase of stathmin1 expression in the brains of schizophrenic patients. These results suggest that up-regulation of stathmin1 in the dentate gyrus, secondary to PACAP deficiency, may create abnormal neuronal circuits that cause abnormal behavior. |
| doi_str_mv | 10.1371/journal.pone.0008596 |
| format | article |
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To clarify the cause of abnormal behavior in PACAP deficient-mice, we attempted the identification of genes whose expression was altered in the dentate gyrus of PACAP-deficient mice using the differential display method. Expression of stathmin1 was up-regulated in the dentate gyrus at both the mRNA and protein levels. PACAP stimulation inhibited stathmin1 expression in PC12 cells, while increased stathmin1expression in neurons of the subgranular zone and in primary cultured hippocampal neurons induced abnormal arborization of axons. We also investigated the pathways involved in PACAP deficiency. Ascl1 binds to E10 box of the stathmin1 promoter and increases stathmin1 expression. Inhibitory bHLH proteins (Hes1 and Id3) were rapidly up-regulated by PACAP stimulation, and Hes1 could suppress Ascl1 expression and Id3 could inhibit Ascl1 signaling. We also detected an increase of stathmin1 expression in the brains of schizophrenic patients. These results suggest that up-regulation of stathmin1 in the dentate gyrus, secondary to PACAP deficiency, may create abnormal neuronal circuits that cause abnormal behavior.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0008596</identifier><identifier>PMID: 20062533</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; ASCL1 protein ; Axons ; Behavior ; Brain ; Child development ; Chromatin Immunoprecipitation ; Dentate gyrus ; Dentate Gyrus - metabolism ; Differential display ; Drosophila ; Female ; Gene expression ; Genes ; Helix-loop-helix proteins (basic) ; Hippocampus ; Hypotheses ; Immunohistochemistry ; Insects ; Laboratories ; Lung cancer ; Male ; Medical imaging ; Medicine ; Mental Health/Child and Adolescent Psychiatry ; Mental Health/Neuropsychiatric Disorders ; Mental Health/Schizophrenia and Other Psychoses ; Mice ; Mice, Knockout ; Microscopy, Immunoelectron ; mRNA ; Neural networks ; Neurobiology ; Neurological Disorders/Developmental and Pediatric Neurology ; Neurological Disorders/Movement Disorders ; Neurological Disorders/Neuropsychiatric Disorders ; Neurons ; Neuroscience/Neurobiology of Disease and Regeneration ; Neuroscience/Neurodevelopment ; Neurosciences ; PC12 Cells ; Pharmaceutical sciences ; Pheochromocytoma cells ; Pituitary adenylate cyclase-activating polypeptide ; Pituitary Adenylate Cyclase-Activating Polypeptide - physiology ; Pregnancy ; Prostate ; Proteins ; Psychiatry ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; RNA, Messenger - genetics ; Rodents ; Schizophrenia ; Serotonin ; Signaling ; Stathmin - genetics ; Stathmin - metabolism ; Stimulation ; Transgenic animals ; Up-Regulation</subject><ispartof>PloS one, 2010-01, Vol.5 (1), p.e8596-e8596</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Yamada et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Yamada et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c789t-a85c53ebf7c6e2f7269a4c8c3eb7edfca31cfea6ec6685f3f9fe18ba562495f13</citedby><cites>FETCH-LOGICAL-c789t-a85c53ebf7c6e2f7269a4c8c3eb7edfca31cfea6ec6685f3f9fe18ba562495f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1289252084/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1289252084?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20062533$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kato, Tadafumi</contributor><creatorcontrib>Yamada, Kohei</creatorcontrib><creatorcontrib>Matsuzaki, Shinsuke</creatorcontrib><creatorcontrib>Hattori, Tsuyoshi</creatorcontrib><creatorcontrib>Kuwahara, Ryusuke</creatorcontrib><creatorcontrib>Taniguchi, Manabu</creatorcontrib><creatorcontrib>Hashimoto, Hitoshi</creatorcontrib><creatorcontrib>Shintani, Norihito</creatorcontrib><creatorcontrib>Baba, Akemichi</creatorcontrib><creatorcontrib>Kumamoto, Natsuko</creatorcontrib><creatorcontrib>Yamada, Kazuo</creatorcontrib><creatorcontrib>Yoshikawa, Takeo</creatorcontrib><creatorcontrib>Katayama, Taiichi</creatorcontrib><creatorcontrib>Tohyama, Masaya</creatorcontrib><title>Increased stathmin1 expression in the dentate gyrus of mice causes abnormal axonal arborizations</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in multiple brain functions. To clarify the cause of abnormal behavior in PACAP deficient-mice, we attempted the identification of genes whose expression was altered in the dentate gyrus of PACAP-deficient mice using the differential display method. Expression of stathmin1 was up-regulated in the dentate gyrus at both the mRNA and protein levels. PACAP stimulation inhibited stathmin1 expression in PC12 cells, while increased stathmin1expression in neurons of the subgranular zone and in primary cultured hippocampal neurons induced abnormal arborization of axons. We also investigated the pathways involved in PACAP deficiency. Ascl1 binds to E10 box of the stathmin1 promoter and increases stathmin1 expression. Inhibitory bHLH proteins (Hes1 and Id3) were rapidly up-regulated by PACAP stimulation, and Hes1 could suppress Ascl1 expression and Id3 could inhibit Ascl1 signaling. We also detected an increase of stathmin1 expression in the brains of schizophrenic patients. These results suggest that up-regulation of stathmin1 in the dentate gyrus, secondary to PACAP deficiency, may create abnormal neuronal circuits that cause abnormal behavior.</description><subject>Animals</subject><subject>ASCL1 protein</subject><subject>Axons</subject><subject>Behavior</subject><subject>Brain</subject><subject>Child development</subject><subject>Chromatin Immunoprecipitation</subject><subject>Dentate gyrus</subject><subject>Dentate Gyrus - metabolism</subject><subject>Differential display</subject><subject>Drosophila</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Helix-loop-helix proteins (basic)</subject><subject>Hippocampus</subject><subject>Hypotheses</subject><subject>Immunohistochemistry</subject><subject>Insects</subject><subject>Laboratories</subject><subject>Lung cancer</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Medicine</subject><subject>Mental Health/Child and Adolescent Psychiatry</subject><subject>Mental Health/Neuropsychiatric Disorders</subject><subject>Mental Health/Schizophrenia and Other Psychoses</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microscopy, Immunoelectron</subject><subject>mRNA</subject><subject>Neural networks</subject><subject>Neurobiology</subject><subject>Neurological Disorders/Developmental and Pediatric Neurology</subject><subject>Neurological Disorders/Movement Disorders</subject><subject>Neurological Disorders/Neuropsychiatric Disorders</subject><subject>Neurons</subject><subject>Neuroscience/Neurobiology of Disease and Regeneration</subject><subject>Neuroscience/Neurodevelopment</subject><subject>Neurosciences</subject><subject>PC12 Cells</subject><subject>Pharmaceutical sciences</subject><subject>Pheochromocytoma cells</subject><subject>Pituitary adenylate cyclase-activating polypeptide</subject><subject>Pituitary Adenylate Cyclase-Activating Polypeptide - physiology</subject><subject>Pregnancy</subject><subject>Prostate</subject><subject>Proteins</subject><subject>Psychiatry</subject><subject>Rats</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>Rodents</subject><subject>Schizophrenia</subject><subject>Serotonin</subject><subject>Signaling</subject><subject>Stathmin - genetics</subject><subject>Stathmin - metabolism</subject><subject>Stimulation</subject><subject>Transgenic animals</subject><subject>Up-Regulation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tq3DAQhk1padK0b1BaQ6GlF7vVwZLsm0IIPSwEAj3dqmN5tOvFtjaSXZI-feWsE9Yl0OILmdE3v6R_ZpLkOSVLyhV9t3WD76BZ7lyHS0JILgr5IDmmBWcLyQh_ePB_lDwJYUuI4LmUj5MjRohkgvPj5OeqMx4hYJWGHvpNW3c0xaudxxBq16V1l_YbTCvs4i6m62s_hNTZtK0NpgaGgCGFsnO-hSaFK9eNiy-dr39DHwXC0-SRhSbgs2k9Sb5__PDt7PPi_OLT6uz0fGFUXvQLyIURHEurjERmFZMFZCY3MaSwsgY4NRZBopEyF5bbwiLNSxCSZYWwlJ8kL_e6u8YFPZkTNGV5wQQjeRaJ1Z6oHGz1ztct-GvtoNY3AefXGnxfmwZ1JfOSC5FDUcmsUgZKLgmDeLSyViqIWu-n04ayxcpEezw0M9H5Tldv9Nr90kwVStLxMm8mAe8uBwy9butgsGmgQzcErTKhqGAZ-TfJucg4VaMFr_4i77dhotYQX1p31sULmlFTn2aKF4zyTEZqeQ8Vvwpj6WPL2TrGZwlvZwmR6fGqX8cWCXr19cv_sxc_5uzrA3aD0PSb4JrhprnmYLYHjXcheLR31aBEjxNz64YeJ0ZPExPTXhxW8i7pdkT4H4jyEkk</recordid><startdate>20100106</startdate><enddate>20100106</enddate><creator>Yamada, Kohei</creator><creator>Matsuzaki, Shinsuke</creator><creator>Hattori, Tsuyoshi</creator><creator>Kuwahara, Ryusuke</creator><creator>Taniguchi, Manabu</creator><creator>Hashimoto, Hitoshi</creator><creator>Shintani, Norihito</creator><creator>Baba, Akemichi</creator><creator>Kumamoto, Natsuko</creator><creator>Yamada, Kazuo</creator><creator>Yoshikawa, Takeo</creator><creator>Katayama, Taiichi</creator><creator>Tohyama, Masaya</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20100106</creationdate><title>Increased stathmin1 expression in the dentate gyrus of mice causes abnormal axonal arborizations</title><author>Yamada, Kohei ; Matsuzaki, Shinsuke ; Hattori, Tsuyoshi ; Kuwahara, Ryusuke ; Taniguchi, Manabu ; Hashimoto, Hitoshi ; Shintani, Norihito ; Baba, Akemichi ; Kumamoto, Natsuko ; Yamada, Kazuo ; Yoshikawa, Takeo ; Katayama, Taiichi ; Tohyama, Masaya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c789t-a85c53ebf7c6e2f7269a4c8c3eb7edfca31cfea6ec6685f3f9fe18ba562495f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>ASCL1 protein</topic><topic>Axons</topic><topic>Behavior</topic><topic>Brain</topic><topic>Child development</topic><topic>Chromatin Immunoprecipitation</topic><topic>Dentate gyrus</topic><topic>Dentate Gyrus - 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Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamada, Kohei</au><au>Matsuzaki, Shinsuke</au><au>Hattori, Tsuyoshi</au><au>Kuwahara, Ryusuke</au><au>Taniguchi, Manabu</au><au>Hashimoto, Hitoshi</au><au>Shintani, Norihito</au><au>Baba, Akemichi</au><au>Kumamoto, Natsuko</au><au>Yamada, Kazuo</au><au>Yoshikawa, Takeo</au><au>Katayama, Taiichi</au><au>Tohyama, Masaya</au><au>Kato, Tadafumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased stathmin1 expression in the dentate gyrus of mice causes abnormal axonal arborizations</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-01-06</date><risdate>2010</risdate><volume>5</volume><issue>1</issue><spage>e8596</spage><epage>e8596</epage><pages>e8596-e8596</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in multiple brain functions. To clarify the cause of abnormal behavior in PACAP deficient-mice, we attempted the identification of genes whose expression was altered in the dentate gyrus of PACAP-deficient mice using the differential display method. Expression of stathmin1 was up-regulated in the dentate gyrus at both the mRNA and protein levels. PACAP stimulation inhibited stathmin1 expression in PC12 cells, while increased stathmin1expression in neurons of the subgranular zone and in primary cultured hippocampal neurons induced abnormal arborization of axons. We also investigated the pathways involved in PACAP deficiency. Ascl1 binds to E10 box of the stathmin1 promoter and increases stathmin1 expression. Inhibitory bHLH proteins (Hes1 and Id3) were rapidly up-regulated by PACAP stimulation, and Hes1 could suppress Ascl1 expression and Id3 could inhibit Ascl1 signaling. We also detected an increase of stathmin1 expression in the brains of schizophrenic patients. These results suggest that up-regulation of stathmin1 in the dentate gyrus, secondary to PACAP deficiency, may create abnormal neuronal circuits that cause abnormal behavior.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20062533</pmid><doi>10.1371/journal.pone.0008596</doi><tpages>e8596</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2010-01, Vol.5 (1), p.e8596-e8596 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1289252084 |
| source | Publicly Available Content Database; PubMed Central |
| subjects | Animals ASCL1 protein Axons Behavior Brain Child development Chromatin Immunoprecipitation Dentate gyrus Dentate Gyrus - metabolism Differential display Drosophila Female Gene expression Genes Helix-loop-helix proteins (basic) Hippocampus Hypotheses Immunohistochemistry Insects Laboratories Lung cancer Male Medical imaging Medicine Mental Health/Child and Adolescent Psychiatry Mental Health/Neuropsychiatric Disorders Mental Health/Schizophrenia and Other Psychoses Mice Mice, Knockout Microscopy, Immunoelectron mRNA Neural networks Neurobiology Neurological Disorders/Developmental and Pediatric Neurology Neurological Disorders/Movement Disorders Neurological Disorders/Neuropsychiatric Disorders Neurons Neuroscience/Neurobiology of Disease and Regeneration Neuroscience/Neurodevelopment Neurosciences PC12 Cells Pharmaceutical sciences Pheochromocytoma cells Pituitary adenylate cyclase-activating polypeptide Pituitary Adenylate Cyclase-Activating Polypeptide - physiology Pregnancy Prostate Proteins Psychiatry Rats Reverse Transcriptase Polymerase Chain Reaction RNA RNA, Messenger - genetics Rodents Schizophrenia Serotonin Signaling Stathmin - genetics Stathmin - metabolism Stimulation Transgenic animals Up-Regulation |
| title | Increased stathmin1 expression in the dentate gyrus of mice causes abnormal axonal arborizations |
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