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Reduced Density of Cholinergic Interneurons in the Ventral Striatum in Schizophrenia: An In Situ Hybridization Study

2005; Elsevier BV; Volume: 58; Issue: 5 Linguagem: Inglês

10.1016/j.biopsych.2005.04.007

1873-2402

Daphne J. Holt, Susan E. Bachus, Thomas M. Hyde, Michael Wittie, Mary M. Herman, Mark Vangel, Clifford B. Saper, Joel E. Kleinman,

Neuroscience and Neuropharmacology Research

Background The role of the striatum in the pathophysiology of schizophrenia is not understood. In a previous postmortem study, we found a reduction in the density of striatal interneurons that stain immunohistochemically for choline acetyltransferase (ChAT) in schizophrenia. Methods To determine whether this finding represents a specific alteration in ChAT gene expression, we used in situ hybridization to study the striatum of 11 control and 9 schizophrenic subjects with oligonucleotide probes complementary to human ChAT mRNA, preprosomatostatin (PPS) mRNA, and β-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and β-actin mRNA expression levels were measured. Results There were no significant differences between the two groups in densities of PPS mRNA-positive neurons and levels of β-actin mRNA expression throughout the striatum, or in densities of ChAT mRNA-positive neurons in the caudate nucleus or putamen. However, in the ventral striatum, the mean density of ChAT mRNA-positive neurons was reduced to 26% of control levels in the schizophrenic group. Conclusions There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia. The role of the striatum in the pathophysiology of schizophrenia is not understood. In a previous postmortem study, we found a reduction in the density of striatal interneurons that stain immunohistochemically for choline acetyltransferase (ChAT) in schizophrenia. To determine whether this finding represents a specific alteration in ChAT gene expression, we used in situ hybridization to study the striatum of 11 control and 9 schizophrenic subjects with oligonucleotide probes complementary to human ChAT mRNA, preprosomatostatin (PPS) mRNA, and β-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and β-actin mRNA expression levels were measured. There were no significant differences between the two groups in densities of PPS mRNA-positive neurons and levels of β-actin mRNA expression throughout the striatum, or in densities of ChAT mRNA-positive neurons in the caudate nucleus or putamen. However, in the ventral striatum, the mean density of ChAT mRNA-positive neurons was reduced to 26% of control levels in the schizophrenic group. There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia.