PhD Scientific Days 2024

Poster Session D - Neurosciences 1.

Selective Induction of Krebs Cycle Enzyme Subunits in the Parahippocampal Cortex of Suicide Victims

Text of the abstract

Altered functional connectivity in human brain networks has been reported in mood disorders. A moderating hub between resting state networks (RSNs) and the medial temporal lobe (MTL) is the parahippocampal cortex (PHC), where abnormal activity has been reported in depressed patients and suicide attempters. Alterations in neuronal mitochondrial function may contribute to depression and suicidal behavior, however, little is known about the underlying molecular level changes in relevant structures. Specifically, expressional changes related to suicide have not been reported in the PHC. Here, we compared the protein expression levels of genes encoding tricarboxylic acid (TCA) cycle enzymes in the PHC of suicide victims by reverse phase protein array (RPPA) and mRNA levels by RT-PCR. Postmortem human brain samples were collected from 12 control and 10 suicide individuals. The entorhinal cortex (EC), topographically anterior to the PHC in the parahippocampal gyrus, served as a control. RPPA analysis revealed that the protein levels of DLD, OGDH, SDHB, SUCLA2 and SUCLG2 subunits were significantly elevated in the PHC but not in the EC. Accordingly, the mRNA levels of respective subunits were also increased. The subunits with altered levels participate in enzyme complexes participating in the oxidative decarboxylation branch of glutamine catabolism. Our data hint on a potential role of glutaminolysis in the PHC in the pathophysiology of suicidal behavior.
Grant support was provided by NAP3 project of the HAS (NAP2022-I-3/2022 and NAP2022-I-4/2022), the NKFIH OTKA K134221, EFOP-3.6.3-VEKOP-16-2017-00009 and TKP2021-EGA-25 grants, the New National Excellence Program and Doctoral Student Scholarship Program of the Co-operative Doctoral Program of NKFIH, and the Gedeon Richter Plc. Centenary Foundation.