Thesis supervisor: Balázs Pál
Location of studies (in Hungarian): University of Debrecen, Faculty of Medicine, Department of Physiology Abbreviation of location of studies: DEÉI
Description of the research topic:
The progressive supranuclear palsy is a neurodegenerative disease characterized by aggregation of tau proteins in cortical and subcortical brain areas. Besides the cognitive decline, motor symptoms resembling Parkinson's disease occur as well. In a mouse model, symptoms of this disease were well modelled by selective lesion of the cholinergic neurons and accumulation of tau proteins in the pedunculopontine nucleus (PPN), a member of the mesencephalic locomotor system. However, besides PPN, other important areas are affected in the disease which are related to movement regulation. Probably the most important one is the substantia nigra.
We plan to investigate how astrocytic activity affects neuronal functions in the substantia nigra under normal conditions and during/after astrocytic overactivation.
The mouse models used for this project will express hM3D chemogenetic actuator, optogenetic actuators and iGluSnFr glutamate sensor in the astrocytes of the substantia nigra (SN). Actions of astrocytic activation on individual SN neurons will be evaluated with slice electrophysiology, in certain cases in a combination with glutamate imaging. Acute activation of astrocytes will be achieved by chemogenetic activation with ip. injection of the designer compound or by optogenetic activation by implanted optical fibers or portable LEDs. Chronic activation will be achieved by long lasting application of the designer compound in the drinking water of the animals. Behavioral tests will include footprint test, activity wheel test, acoustic startle test, Barnes maze test and drug preference test. Tests are followed by morphological analysis of astrocytes and neurons. We will check changes of extrasynaptic glutamate under different conditions by in vivo fluorescent imaging.
We will demonstrate how astrocytic activation acts on the neuronal networks of the SN and whether astrocytic overactivation can model progressive supranuclear palsy. We try to slower the possible progress of the disease by pharmacological inhibition astrocytic glutamate release.
Required language skills: English intermediate level Number of students who can be accepted: 1
Deadline for application: 2024-05-15
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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