Estudio de la actividad neuronal de la corteza auditiva en un modelo animal de enfermedad mental con displasia cortical

Zusammenfassung

STUDY OF NEURONAL ACTIVITY OF THE HEARING CORTEX IN AN ANIMAL MODEL OF MENTAL DISEASE WITH CORTICAL DYSPLASIA ABSTRACT INTRODUCTION.- The etiopathogenesis of schizophrenia is unknown, but currently the most accepted hypothesis it is related with the neuronal development disorders. Several studies report that morpho-pathological alterations of the frontal and temporal cortex in schizophrenic patients would be compatible with anomalies in the neuronal migration processes. LIS1 protein and phospholipid platelet activating factor (PAF) play an important role in neuronal migration during the cerebral cortex development, so it is possible that both could be altered in some way in psychotic patients. HYPOTHESIS.- Under basal conditions, the significant decrease of interneurones in the superficial layers of the cerebral cortex and the primary auditory cortex (A1) could increase neuronal activity in mutant mouse (Lis1/sLis1) compare to Wild Type (WT) mouse. The study of the auditory area of the human brain with lysencephaly would show the same deficiency of inhibitory neurons in the superficial layers of the cortex, which would allow us to speculate with the possibility of this anomaly in the neuronal migration as the base of auditory hallucinations in schizophrenia. OBJECTIVES.- To describe the structural alterations of the auditory cortex and to study the basal activity of the auditory cortex of the Lis1/sLis1 mutant mice. To describe the structural alterations of the temporal cortex in the brain of a patient diagnosed with lysencephaly type I. To develop a physiopathological hypothesis to explain the structural abnormalities may be involved in auditory hallucinations in schizophrenia. MATERIAL AND METHODS.- We study the auditory cortex of these mice under normal ambient noise conditions and evaluated the activation of cortical neurons in a non-specific excitation state. We analyze gene expression by rapid response (c-fos) neuronal activity. To do this, we will use the following groups: A.) Control group mice: 10 WT mice. B.) Experimental mice: 10 Lis1 / sLis1 mutant mice. Experimental design: - Morphological study of the auditory cortex of heterozygous mutants by immunohistochemistry and cytoarchitectural stains. - Determination of c-fos expression as a marker of neuronal activity in the auditory cortex under normal conditions. In WT and Lis1/sLis1 mice under the same ambient noise conditions. For the quantification, the Image J program was used and the statistical analysis was performed with the Sigmaplot v11.0 program. Paired comparisons of mean counts of c-fos positive cells between the mutant Lis1 / sLis1 and WT were performed. Data were compared as mean plus standard error using Student's t-test. - Morphological study of the auditory cortex of a human brain diagnosed with lysencephaly. RESULTS AND CONCLUSIONS.- In WT mice, A1 cortex show a less number of cells with intense expression of c-fos, mainly in layer II and V. In the mutant mouse Lis1 / sLis1, a large increase of intensely c-fos positive neurons is observed in Layers II, IV and V (P0.05). The auditory cortex of the mutant mouse Lis1 / sLis1 presents an alteration of the migration of the GABAergic interneurons in the cortex A1. Futhermore has an increased activity of A1 cortex neurons under basal ambient noise conditions. The temporal cortex of a human brain with lysencephaly type I presents an alteration of the migration of the GABAergic neurons of the superficial layers. The similarities observed in our study between the A1 cortex of the Lis1 / sLis1 mouse and the temporal cortex of the human with lisencephaly could provide us a model for the study of neurobiological causes related with auditory hallucinations.