IDENTIFYING IMPAIRED CORTICAL NEURONAL POPULATIONS IN SCHIZOPHRENIA WITH IMMUNOHISTOCHEMISTRY AND RNA-SCOPE
01/29/2020
Teadora Tyler1, Lilla Roszik1, Erzsebet Frank1, Virginia Feher1, Dora Mandic2, Zdravko Petanjek2, Istvan Adorjan1, 3
1 Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest
2 Croatian Institute for Brain Research, University of Zagreb, Zagreb
3 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford
The current view on the etiology of neuropsychiatric disorders, such as schizophrenia, holds that excitatory/inhibitory imbalance plays a major role in these conditions. The most investigated brain region is the dorsolateral prefrontal cortex (Brodmann area 9) in schizophrenia. Although extensively studied, there is no consensus on alterations present at neuronal population level. Most post-mortem studies on the prefrontal cortex from patients with schizophrenia did not find any significant change in the density of major interneuronal subclasses such as calretinin, calbindin or parvalbumin. However, when taking into account the hippocampal and anterior cingulate cortex, the parvalbumin-immunoreactive population was found to be decreased. Our work reveals characteristic neuroanatomical phenotypes with changes in the distribution and density of specific interneurons such as the calretinin- and parvalbumin-immunoreactive populations. Considering the layerwise distribution of the aforementioned neuronal subtypes, layer 2 and 3 were particularly affected. These results were confirmed by RNA-scope experiments revealing the spatial distribution of impaired populations in the dorsolateral prefrontal cortex. Our study provides the comprehensive landscape on cortical neuronal populations in schizophrenia based on a multidisciplinary approach employing quantitative immunohistochemical analysis and RNA-scope.