PhD Scientific Days 2025

Poster Session III. - R: Neurosciences

Transcriptional Profiling of the Parahippocampal Cortex (PHC) in Suicide Victims

Name of the presenter

Hajdu Tamara

Institute/workplace of the presenter

Semmelweis University Department of Anatomy, Histology and Embryology

Authors

Tamara Hajdu¹, Fanni Dóra^1,2, Éva Renner², Alán Alpár^2,3, Miklós Palkovits², Árpád Dobolyi¹

1: Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest 1094, Hungary
2: Human Brain Tissue Bank, Semmelweis University, Budapest 1094, Hungary
3: Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest 1094, Hungary

Text of the abstract

Suicide represents a critical outcome in mental diseases, often marked by dysregulated neural network dynamics, particularly within the default mode network (DMN). The parahippocampal cortex (PHC), a DMN hub region, modulates processes ranging from episodic memory to emotional responses. Enhanced PHC activity has been recorded in suicide attempters, and our prior proteomic work highlights mitochondrial glutaminolytic anomalies in the PHC, however, the transcriptomic architecture underlying suicidal behaviour remains still unexamined.
This study aimed to identify transcriptional alterations in the PHC associated with suicidal behavior integrating RNA sequencing and targeted validation to map the major molecular mechanisms. Postmortem PHC tissues from 11 suicide decedents and 11 demographically matching controls underwent RNA extraction. Differential gene expression was analyzed via the DESeq2 software package.
Transcriptional profiling identified 201 downregulated and 171 upregulated genes (|L2FC| > 1, padj < 0.05). The Gene Ontology (GO) enrichment, the STRING protein-protein interaction (PPI) network and the Reactome Pathway analysis of downregulated genes highlighted deficits in ATP synthesis and G protein-coupled receptor signalling indicating mitochondrial and synaptic inefficiency. The PPI mapping showed suppressed chemokine pathway suggesting attenuated neuroimmunity. Conversely, the GO annotation and the PPI network analysis revealed that the upregulated genes implicated hyperactive axonal myelination pointing to altered neural connectivity. The subsequent qRT-PCR examinations revealed a very high correlation with sequencing data and confirmed diminished oxytocin receptor (OXTR), oxidative phosphorylation (MT-ATP6, MT-ND4), and the adhesion G protein-coupled receptor G7 (ADGRG7), alongside elevated gliomedin (GLDN), ichthyin (NIPAL4), and plakophilin-1 (PKP1) in suicide.
These findings define a PHC-specific molecular signature in suicide characterized by dysregulated neuroimmune crosstalk, mitochondrial bioenergetics, and aberrant myelination offering novel therapeutic advances.
Funding: NAP3 project of the HAS (NAP2022-I-3/2022 and NAP2022-I-4/2022), NKFIH OTKA K146077 and OTKA National Research Excellence program 151425, TKP2021-EGA-25, and Gedeon Richter Talentum Foundation in framework of Gedeon Richter Excellence PhD Scholarship.