SzSA YearBook 2018/19

SZENT-GYÖRGYI JUNIOR MENTORS
ÁKOS MENYHÁRT
Group of Cerebral Blood Flow and Metabolism,
Department of Medical Physics and Informatics,
University of Szeged
Address: Korányi fasor 8-10, H-6720 Szeged, Hungary
RESEARCH AREA
Glutamate excitotoxicity and cellular calcium overload
stand in the background of various neurological disorders
such as cerebral stroke, traumatic brain injury, epilepsy or
Parkinson’s disease. While neurons are highly sensitive to
ischemic injury, their more resistant protectors, astrocytes
are essential to restore glutamatergic signaling to the
physiological range. Astrocytes modulate neural excitability
and minimize brain damage through spatial buffering of
extracellular K+ and clearance of surplus neurotransmitters.
The most important trait of astrocytes is probably the
formation of an anatomical and functional “syncytium”,
a network created by cells attached to each other to
communicate by gap junctions (GJs). The anatomical
continuity of the main GJ proteins; Cx43 and Cx30, is
essential to/for the formation of the functional syncytium
of astrocytes. Phosphorylation of Cx43 essentially reduces
the conductance of GJs, and thereby affects interastrocytic
communication by altering gating and trafficking properties
of the channels.
Spreading depolarization (SD) is a slowly propagating wave
of neuronal and glial depolarization that occurs in the injured
brain and contributes to lesion expansion after ischemic
stroke. We have recently found impaired extracellular
potassium clearance during spreading depolarization
under simulated ischemic conditions. According to our
working hypothesis; SD causes CX43 phosphorylation,
reduces astrocytic spatial buffering capacity, and impairs
glutamate clearance and excitotoxicity in the ischemic
brain. Therefore, the major goals of our research are;
1. To demonstrate that astrocyte Cx43 phosphorylation
co-occurs with impaired spatial buffering and glutamate
clearance in global cerebral ischemia;
2. To improve cellular viability and achieve better outcome
from cerebral ischemic injury.
TECHNIQUES AVAILABLE IN THE LAB
Application of the Biopac© and LabChart© systems for
data acquisition and analysis, basic experimental surgical
techniques, electrophysiology (DC potential and EEG
recording, measurement of pH and extracellular potassium
concentration in the nervous tissue), experimental
microsurgery, image analysis, in vitro brain slice preparation,
intrinsic optical signal analysis, laser Doppler flowmetry,
laser-speckle contrast imaging of local cerebral blood flow,
pharmacology, statistical methods, computer programming
(MATlab) voltage-sensitive and pH-sensitive dye imaging of
cellular trans-membrane potential.
SELECTED PUBLICATIONS
Menyhárt, Á., Zölei-Szénási, D., Puskás T., Makra, P., Bari,
F., Farkas, E. (2017) Age or ischemia uncouples the blood
flow response, tissue acidosis, and direct current potential
signature of spreading depolarization in the rat brain. Am J
Physiol Heart Circ Physiol 313(2): H328-H337.
Menyhárt, Á., Zölei-Szénási, D., Puskás, T., Makra, P., Orsolya,
M.T., Szepes, B.É., Tóth, R., Ivánkovits-Kiss, O., Obrenovitch,
T.P., Bari, F., Farkas, E. (2017) Spreading depolarization
remarkably exacerbates ischemia-induced tissue acidosis in
the young and aged rat brain. Sci Rep 7(1): 1154.
Varga, D.P., Puskás, T., Menyhárt, Á., Hertelendy, P., Zölei-
Szénási, D., Tóth, R., Ivánkovits-Kiss, O., Bari, F., Farkas, E.
(2016) Contribution of prostanoid signaling to the evolution
of spreading depolarization and the associated cerebral
blood flow response. Sci Rep 6: 31402.
Menyhárt, Á., Makra, P., Szepes, B.É., Tóth, O.M., Hertelendy,
P., Bari, F., Farkas, E. (2015) High incidence of adverse
cerebral blood flow responses to spreading depolarization
in the aged ischemic rat brain. Neurobiol Aging 36(12):
3269-3277.
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