[A role for microtubules in mental diseases?].
Microtubules are key cytoskeletal components in the cytoplasm of eukaryotic cells where they have pleiotropic and vital roles in functions such as cell division, trafficking or morphogenesis. Microtubules are especially abundant in neurons. Although microtubules are in many cells dynamic polymers, they exhibit an extreme state of stability in neurons. Previous work has indicated a central role of microtubule associated proteins called STOPs in neuronal microtubule stabilization. We have recently developed STOP null mice. These mice were devoid of stable brain microtubules but to our surprise had nevertheless an apparently normal brain anatomy. However the mice showed synaptic defects affecting different forms of long- and short-term synaptic plasticity. These synaptic defects were associated with severe behavioral defects that showed a remarkable sensitivity to long-term treatment with neuroleptics. We discuss the relationship of the phenotypes observed in STOP null mice with current models of schizophrenia in which the multiple, severe, and neuroleptic sensitive mental disorders caused by the disease are due to a "disease of the synapse".
Laboratoire du cytosquelette, département des réponses dynamiques et cellulaires, CEA-Grenoble, Inserm U366, 17, avenue des Martyrs, 38054 Grenoble, France.
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D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003599:Cytoskeleton / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008870:Microtubules / Q000502:physiology*; D008954:Models, Biological; D008959:Models, Neurological; D009473:Neuronal Plasticity; D009474:Neurons / Q000648:ultrastructure*; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology; D014404:Tubulin / Q000378:metabolism
D014150:Antipsychotic Agents; C491894:MAP6 protein, human; D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse; D014404:Tubulin