Lower number of cerebellar Purkinje neurons in psychosis is associated with reduced reelin expression

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 9; pp. 4407 - 4411
• Main Authors: Maloku, Ekrem, Covelo, Ignacio R, Hanbauer, Ingeborg, Guidotti, Alessandro, Kadriu, Bashkim, Hu, Qiaoyan, Davis, John M, Costa, Erminio
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02.03.2010; National Acad Sciences
• Subjects: adults; Aged; Animals; Antipsychotic agents; Biological Sciences; Bipolar Disorder - metabolism; Bipolar Disorder - pathology; Brain; Cell Adhesion Molecules, Neuronal - metabolism; Cells; Cerebellum; Cohort Studies; Comparative studies; Down regulation; extracellular matrix; Extracellular Matrix Proteins - metabolism; Female; gene expression regulation; heterozygosity; Humans; illicit drugs; In Situ Hybridization; Linear density; Male; Mental disorders; Messenger RNA; Mice; Middle Aged; Nerve Tissue Proteins - metabolism; Neurons; patients; protein synthesis; Proteins; Psychosis; Purkinje cells; Purkinje Cells - pathology; Receptors; Rodents; Schizophrenia; Schizophrenia - metabolism; Schizophrenia - pathology; Serine Endopeptidases - metabolism; Tissues
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0914483107

Reelin is an extracellular matrix protein synthesized in cerebellar granule cells that plays an important role in Purkinje cell positioning during cerebellar development and in modulating adult synaptic function. In the cerebellum of schizophrenia (SZ) and bipolar (BP) disorder patients, there is a marked decrease ([almost equal to]50%) of reelin expression. In this study we measured Purkinje neuron density in the Purkinje cell layer of cerebella of 13 SZ and 17 BP disorder patients from the McLean 66 Cohort Collection, Harvard Brain Tissue Resource Center. The mean number of Purkinje neurons (linear density, neurons per millimeter) was 20% lower in SZ and BP disorder patients compared with nonpsychiatric subjects (NPS; n = 24). This decrease of Purkinje neuron linear density was unrelated to postmortem interval, pH, drugs of abuse, or to the presence, dose, or duration of antipsychotic medications. A comparative study in the cerebella of heterozygous reeler mice (HRM), in which reelin expression is down-regulated by [almost equal to]50%, showed a significant loss in the number of Purkinje cells in HRM (10-15%) compared with age-matched (3-9 months) wild-type mice. This finding suggests that lack of reelin impairs GABAergic Purkinje neuron expression and/or positioning during cerebellar development.