Neurosciences
Dr. Balázs Pósfai, PhD
Institute of Experimental Medicine
+36303313010
posfai.balazs@koki.hu
Loss of Microglial P2Y12 Receptor Scales with Severity of Neurological Diseases
Balázs Pósfai1, Sára Vida1, Krisztina Tóth1, Cecília Szekeres-Paraczky1, Zsófia Maglóczky1, Ana Rita Brás1, Péter Gombás2, Lóránd Erőss3, Ádám Dénes1
1: Institute of Experimental Medicine
2: Department of Pathology, St. Borbála Hospital, Tatabánya
3: Institute of Neurosurgery and Neurointervention, Faculty of Medicine, Semmelweis University
Szóbeli
Neurosciences
English
Neurosciences
Introduction: Understanding the mechanisms of neurological diseases is one of the most urgent challenges of medicine. In recent years, our workgroup has contributed to the understanding of the homeostatic and neuroprotective roles of microglia, the brain’s main immune cell under both physiological and pathological conditions. The microglia-specific purinergic P2Y12 receptor is essential in microglial homeostatic functions, and a key element of intercellular communication with neurons and vascular elements. Unveiling alterations in P2Y12 receptor expression levels in global (e.g. Alzheimer’s disease) and focal (e.g. epilepsy) neuropathologies leads to a better understanding of these disorders.
Aims: To assess microglial P2Y12 receptor expression levels in different human neurological pathologies.
Methods: In this study we utilized human brain samples from different sources: for the epilepsy investigations, control human tissues were obtained from subjects who died from causes not directly involving any brain disease, autopsies took place in Saint Borbála Hospital, Tatabánya. Patients with drug resistant temporal lobe epilepsy underwent surgery in the National Institute of Clinical Neurosciences in Budapest, within the framework of the Hungarian Epilepsy Surgery Program. For the Alzheimer’s disease analysis, control and pathological samples were obtained from the Netherlands Brain Bank. We performed immunofluorescent labelling and single cell RNA sequencing on a subset of the samples.
Results and conclusions: Our results show that P2Y12 receptor expression scales with the severity of disease in human epilepsy: patients with hippocampal sclerosis show lower levels of P2Y12 receptor expression in their temporal cortex, and microglia-neuron contacts are significantly altered mimicking changes seen in P2Y12 receptor-deficient mice. In the Alzheimer’s patients, single cell RNA sequencing revealed a drastic loss of microglial P2Y12 receptor, accompanied by a shift in the ratio of microglial subtypes.
Funding: Supported by the EKÖP-2024-67 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund and SORLA-FIX JPND.
Semmelweis University
Ádám Dénes
I do not give consent to the publication of my abstract on the website of the congress.
after finishing doctoral studies with absolutorium (PhD)
Szabad
elfogadva
szóbeli
nem hagyta jóvá
8930
09:00
09:15