Implication of neuronal Ca2+ -sensor protein VILIP-1 in the glutamate hypothesis of schizophrenia.
Neurobiol Dis
; 32(1): 162-75, 2008 Oct.
Article
em En
| MEDLINE
| ID: mdl-18691652
ABSTRACT
Post mortem studies in the hippocampus of schizophrenia patients revealed increased expression of neuronal Ca(2+)-sensor VILIP-1 (visinin-like protein) and enhanced co-localization with alpha4beta2 nAChR in interneurons. To study the pathological role of VILIP-1, particularly in interneurons, in the context of the glutamate hypothesis of schizophrenia, we have used ketamine-treated rats, a NMDA receptor hypofunction model, and hippocampal cultures as model systems for schizophrenia. Treatment with ketamine leads to enhanced VILIP-1 expression in interneurons in rat hippocampal CA1 region. In cultures glutamate treatment led to an increase in VILIP-1-positive interneurons, which is not dependent on NMDA receptor but metabotropic glutamate receptor activation. VILIP-1 mainly co-localizes with the interneuron marker calretinin, mGluR1alpha and the VILIP-1 interaction partner alpha4beta2 nAChR in hippocampal slices. Overexpression of VILIP-1 leads to enhanced nAChR-dependent inhibitory postsynaptic current (IPSC) generation by interneurons. This novel molecular link between the pathological role of mGluRs, VILIP-1 and its interaction partner alpha4beta2 nAChR by converging pathological glutamatergic and nicotinergic transmission may underlie cognitive impairments in schizophrenia.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
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Cálcio
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Ácido Glutâmico
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Proteínas Sensoras de Cálcio Intracelular
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Neurocalcina
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Hipocampo
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Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article