PhD Scientific Days 2022

Neurosciences I. (Poster discussion will take place in the Aula during the Coffee Break)

Prefrontal Calretinin and Parvalbumin Interneurons in Schizophrenia

Text of the abstract

Introduction: Excitatory/inhibitory imbalance plays a major role in neuropsychiatric disorders such as schizophrenia (SCH). The prefrontal cortex had been studied extensively, yet there is no consensus on alterations regarding interneuronal composition in patients with SCH. In the last decades several independent workgroups observed both decreased and unchanged densities of parvalbumin (PV+) neurons and only one study reported the decreased density of calretinin (CR+) neurons in the Brodmann area 9 in SCH. Recently, several single cell RNA sequencing studies have also tried to elucidate the molecular background of SCH.

Aim: We aim to give a comprehensive view of all major interneuronal cell types in the dorsolateral prefrontal cortex (DLPFC) and their possible impairment in SCH.

Methods: Formalin-fixed tissue from 15 cases with SCH and 15 age- and gender matched control (CTR) cases obtained from several brain banks was immunohistochemically stained. We quantified CR+ and PV+ neurons in cortical columns after delineating cortical layers based on Nissl staining. Linear mixed models were applied for statistical evaluation of layerwise density values.

Results: CR+ interneuron density was significantly lower in cortical layer II of the SCH group. Interestingly, the SCH samples could be subdivided into a ‘control-like’ group with no density reduction and an ‘affected’ group with considerably lower density values, not confounded by age, gender or post mortem interval (PMI). PV+ cell density was also reduced; however, it was strongly correlated with PMI.

Conclusion: It is important to further study within-group differences as it may lead to the better understanding of schizophrenia. Cell types identified as impaired can be subjects of targeted experiments such as iPSC assays and organoid models, which hold the potential of revealing neurodevelopmental mechanisms underlying illness in postnatal life.

Funding: The project was funded by the Institutional Excellence in Higher Education Grant (FIKP, Semmelweis University), Semmelweis Fund for Science and Innovation, Semmelweis Departmental Start-up Grant, the Science and Technology Fund 2019-2021 (NKFIH), the ÚNKP-21 Bolyai/Bolyai+ Grants, and the Thematic Excellence Programme 2021.