The suppression of brain cold-stable microtubules in mice induces synaptic defects associated with neuroleptic-sensitive behavioral disorders
Neurons contain abundant subsets of highly stable microtubules that resist depolymerizing conditions such as exposure to the cold. Stable microtubules are thought to be essential for neuronal development, maintenance, and function. Previous work has indicated an important role of the microtubule-ass...
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| Veröffentlicht in: | Genes & development 2002-09, Vol.16 (18), p.2350-2364 |
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| creator | Andrieux, Annie Salin, Paul A Vernet, Muriel Kujala, Pekka Baratier, Julie Gory-Fauré, Sylvie Bosc, Christophe Pointu, Hervé Proietto, Dominique Schweitzer, Annie Denarier, Eric Klumperman, Judith Job, Didier |
| description | Neurons contain abundant subsets of highly stable microtubules that resist depolymerizing conditions such as exposure to the cold. Stable microtubules are thought to be essential for neuronal development, maintenance, and function. Previous work has indicated an important role of the microtubule-associated protein STOP in the induction of microtubule cold stability. Here, we developed STOP null mice. These mice were devoid of cold-stable microtubules. In contrast to our expectations, STOP-/- mice had no detectable defects in brain anatomy but showed synaptic defects, with depleted synaptic vesicle pools and impaired synaptic plasticity, associated with severe behavioral disorders. A survey of the effects of psychotropic drugs on STOP-/- mice behavior showed a remarkable and specific effect of long-term administration of neuroleptics in alleviating these disorders. This study demonstrates that STOP is a major factor responsible for the intriguing stability properties of neuronal microtubules and is important for synaptic plasticity. Additionally, STOP-/- mice may yield a pertinent model for study of neuroleptics in illnesses such as schizophrenia, currently thought to result from synaptic defects. |
| doi_str_mv | 10.1101/gad.223302 |
| format | Article |
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Stable microtubules are thought to be essential for neuronal development, maintenance, and function. Previous work has indicated an important role of the microtubule-associated protein STOP in the induction of microtubule cold stability. Here, we developed STOP null mice. These mice were devoid of cold-stable microtubules. In contrast to our expectations, STOP-/- mice had no detectable defects in brain anatomy but showed synaptic defects, with depleted synaptic vesicle pools and impaired synaptic plasticity, associated with severe behavioral disorders. A survey of the effects of psychotropic drugs on STOP-/- mice behavior showed a remarkable and specific effect of long-term administration of neuroleptics in alleviating these disorders. This study demonstrates that STOP is a major factor responsible for the intriguing stability properties of neuronal microtubules and is important for synaptic plasticity. Additionally, STOP-/- mice may yield a pertinent model for study of neuroleptics in illnesses such as schizophrenia, currently thought to result from synaptic defects.</description><identifier>ISSN: 0890-9369</identifier><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.223302</identifier><identifier>PMID: 12231625</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Animals ; Anti-Anxiety Agents - pharmacology ; Antipsychotic Agents - pharmacology ; Behavior, Animal - drug effects ; Behavior, Animal - physiology ; Brain - pathology ; Brain - physiopathology ; Cold Temperature ; Disease Models, Animal ; Female ; Humans ; Male ; Mice ; Mice, Knockout ; Microscopy, Electron ; Microtubule-Associated Proteins - deficiency ; Microtubule-Associated Proteins - genetics ; Microtubule-Associated Proteins - physiology ; Microtubules - pathology ; Microtubules - physiology ; Neuronal Plasticity ; Research Paper ; Synapses - pathology ; Synapses - physiology ; Synaptic Transmission</subject><ispartof>Genes & development, 2002-09, Vol.16 (18), p.2350-2364</ispartof><rights>Copyright © 2002, Cold Spring Harbor Laboratory Press 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-4721d044fec64ae27ac25367c28668e752733be95d538eea1e9f796250ae607b3</citedby><cites>FETCH-LOGICAL-c404t-4721d044fec64ae27ac25367c28668e752733be95d538eea1e9f796250ae607b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC187434/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC187434/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12231625$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Andrieux, Annie</creatorcontrib><creatorcontrib>Salin, Paul A</creatorcontrib><creatorcontrib>Vernet, Muriel</creatorcontrib><creatorcontrib>Kujala, Pekka</creatorcontrib><creatorcontrib>Baratier, Julie</creatorcontrib><creatorcontrib>Gory-Fauré, Sylvie</creatorcontrib><creatorcontrib>Bosc, Christophe</creatorcontrib><creatorcontrib>Pointu, Hervé</creatorcontrib><creatorcontrib>Proietto, Dominique</creatorcontrib><creatorcontrib>Schweitzer, Annie</creatorcontrib><creatorcontrib>Denarier, Eric</creatorcontrib><creatorcontrib>Klumperman, Judith</creatorcontrib><creatorcontrib>Job, Didier</creatorcontrib><title>The suppression of brain cold-stable microtubules in mice induces synaptic defects associated with neuroleptic-sensitive behavioral disorders</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>Neurons contain abundant subsets of highly stable microtubules that resist depolymerizing conditions such as exposure to the cold. Stable microtubules are thought to be essential for neuronal development, maintenance, and function. Previous work has indicated an important role of the microtubule-associated protein STOP in the induction of microtubule cold stability. Here, we developed STOP null mice. These mice were devoid of cold-stable microtubules. In contrast to our expectations, STOP-/- mice had no detectable defects in brain anatomy but showed synaptic defects, with depleted synaptic vesicle pools and impaired synaptic plasticity, associated with severe behavioral disorders. A survey of the effects of psychotropic drugs on STOP-/- mice behavior showed a remarkable and specific effect of long-term administration of neuroleptics in alleviating these disorders. This study demonstrates that STOP is a major factor responsible for the intriguing stability properties of neuronal microtubules and is important for synaptic plasticity. 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| issn | 0890-9369 1549-5477 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Anti-Anxiety Agents - pharmacology Antipsychotic Agents - pharmacology Behavior, Animal - drug effects Behavior, Animal - physiology Brain - pathology Brain - physiopathology Cold Temperature Disease Models, Animal Female Humans Male Mice Mice, Knockout Microscopy, Electron Microtubule-Associated Proteins - deficiency Microtubule-Associated Proteins - genetics Microtubule-Associated Proteins - physiology Microtubules - pathology Microtubules - physiology Neuronal Plasticity Research Paper Synapses - pathology Synapses - physiology Synaptic Transmission |
| title | The suppression of brain cold-stable microtubules in mice induces synaptic defects associated with neuroleptic-sensitive behavioral disorders |
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