کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4181063 1276632 2006 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Microtubule Stabilizer Ameliorates Synaptic Function and Behavior in a Mouse Model for Schizophrenia
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Microtubule Stabilizer Ameliorates Synaptic Function and Behavior in a Mouse Model for Schizophrenia
چکیده انگلیسی

BackgroundRecent data suggest that cytoskeletal defects may play a role in schizophrenia. We previously imitated features of schizophrenia in an animal model by disrupting gene coding for a microtubule-associated protein called STOP. STOP-null mice display synaptic defects in glutamatergic neurons, hyper-dopaminergy, and severe behavioral disorders. Synaptic and behavioral deficits are amended by neuroleptic treatment in STOP-null mice, providing an attractive model to test new antipsychotic agents. We examined the effects of a taxol-related microtubule stabilizer, epothilone D.MethodsMice were treated either with vehicle alone or with epothilone D. Treatment effects on synaptic function were assessed using electron-microscopy quantification of synaptic vesicle pools and electrophysiology in the CA1 region of the hippocampus. Dopamine transmission was investigated using electrochemical assays. Behavior was principally assessed using tests of maternal skills.ResultsIn STOP-null mice, treatment with epothilone D increased synaptic vesicle pools, ameliorated both short- and long-term forms of synaptic plasticity in glutamatergic neurons, and had a dramatic beneficial effect on mouse behavior.ConclusionsA microtubule stabilizer can have a beneficial effect on synaptic function and behavior, suggesting new possibilities for treatment of schizophrenia.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 60, Issue 11, 1 December 2006, Pages 1224–1230
نویسندگان
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