Implication of neuronal Ca2+ -sensor protein VILIP-1 in the glutamate hypothesis of schizophrenia.

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.

• Authors: Paul Gierke, Congjian Zhao, Hans-Gert Bernstein, Cornelia Noack, Rene Anand, Uwe Heinemann, Karl-Heinz Braunewell
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 32 Issue 1 Pg. 162-75 (Oct 2008) ISSN: 1095-953X [Electronic] United States
• PMID: 18691652 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intracellular Calcium-Sensing Proteins
• Neurocalcin
• Receptors, Metabotropic Glutamate
• Receptors, Nicotinic
• VSNL1 protein, human
• metabotropic glutamate receptor type 1
• nicotinic receptor alpha4beta2
• Glutamic Acid
• Ketamine
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Cells, Cultured
• Dentate Gyrus (metabolism)
• Female
• Glutamic Acid (metabolism, physiology)
• Hippocampus (metabolism, pathology)
• Humans
• Interneurons (metabolism, pathology)
• Intracellular Calcium-Sensing Proteins (metabolism)
• Ketamine (administration & dosage)
• Male
• Neurocalcin (metabolism)
• Neurons (metabolism, pathology)
• Rats
• Rats, Wistar
• Receptors, Metabotropic Glutamate (metabolism, physiology)
• Receptors, Nicotinic (metabolism)
• Schizophrenia (metabolism, pathology)