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Investigating the role of purinergic receptors in the pathophysiology of schizophrenia using human induced pluripotent stem cell (IPSC)-based in vitro model

Collaboration with the group of Prof. János Réthelyi, M.D., Ph.D. (Department of Psychiatry and Psychotherapy, SE)

Extracellular purines and pyrimidines are key neurotransmitters and neuromodulators of the central and peripheral nervous systems. They act pre- and postsynaptically through purinergic receptors classified as P1 and P2 receptors. P1 receptors are adenosine receptors, whereas P2 receptors are activated by other extracellular purine and pyrimidine nucleotides such as ATP, ADP, UTP, UDP or UDP-glucose.

The present hypotheses about the etiology of schizophrenia include both the dysfunctions of the mesocorticolimbic dopamine system and the glutamatergic afferents from the prefrontal cortex to the ventral tegmental area. As purinergic signaling modulates dopaminergic and glutamatergic neurotransmission in the brain, the impaired function of this system might be involved in the development of schizophrenia.

Fibroblasts from patients affected by schizophrenia and from their healthy relatives are reprogrammed into induced pluripotent stem cells (IPSCs) in the laboratory of our collaborators. IPSCs are further differentiated into mature, postmitotic neuron-like phenotype. Our group is planning to examine the mRNA and protein expressions of purinergic receptors in the different stages of this maturation process by quantitative RT-PCR and immunocytochemistry, respectively. Furthermore, we are interested in the functional analyses of distinct purinergic receptors using patch clamp electrophysiology.

Learning opportunity to acquire skills in the following techniques: quantitative RT-PCR, immunocytochemistry, patch clamp electrophysiology.