Інститут біохімії ім. О.В Палладіна НАН України

Palladin Institute of Biochemistry of the NAS of Ukraine

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Department of Neurochemistry


Head – Nina H. Himmelreich,
Ph.D.
Tel.:+ (380-44) 234-32-54

Current project:

Regulatory mechanisms and modulatory pathways of presynaptic processes: release and transmembrane transport of neurotransmitters as key steps of neurotransmission

The present study is aimed at uncovering mechanisms for regulation of glutamate and GABA release from nerve terminals and transporter-mediated fluxes of the neurotransmitter molecules across the plasma membrane, and at analysis of conditions
causing the transporter-mediated neurotransmitter fluxes in reversed direction. Our efforts are focused on the following topics: a role of plasma membrane structure, particularly the role of membrane cholesterol, in the transporter-mediated fluxes
of neurotransmitter molecules through the plasma membrane, in exocytotic process as a whole and in fusion of the synaptic vesicles with plasma membrane; a role of presynaptic receptors in modulation of neurotransmission; testing of venoms
for searching new natural neuroactive compounds. Main experiments are performed with using nerve terminals of neurons from different area of rat brain, cell-free model system consisting of synaptic vesicles and plasma membrane fraction, bilayer lipid membrane.

Effect of perinatal hypoxia, as factor of producing long-lasting changes in seizure susceptibility, on presynaptic plasma membrane GABA transportes and receptors.

In this study, our main efforts are aimed at understanding consequences of damage of the premature brain by hypoxia, a naturally occurring form of perinatal injury. For understanding whether neonatal GABA-ergic neurons are affected by
perinatal brain insults at least three topics are in focus of our attention: a level of ATP; activity and kinetic properties of a process of GABA reuptake via plasma membrane GABA transporters and release of GABA by exocytosis; role of presynaptic GABA receptors in development of consequences evoked by perinatal hypoxia.Experiments are performed using nerve terminals of cortex, hippocampus and thalamus of rat brain.

STCU Project P-322
Partner- U.S. Environmental Protection Agency
Regional evaluation of mining-related metals contamination, risks, and innovative remediation technologies in Ukraine and Georgia. Effects of the mining waste metals on the glutamatergic and GABA ergic transmission in brain.

The goal of this research is to estimate the neurotoxicity risks for health from exposure to manganese, lead and cadmium, the major mining contaminant metals that are present in today's environment of Tchiature region of Georgia and Kryvyi Rig basin of Ukraine. The importance of studying is underscored by the role of these mining metals as risk factors in early dysfunction of brain, neurotoxicity and development of the neurodegenerative diseases. An effective strategy for identification of risk factors and designing neurotoxicity prevention strategies would be the investigations of mining waste metal effects on the
glutamatergic and GABAergic transmission using isolated nerve terminals from rat brain as tools.

Project « Neuron » within the frame of the National Space Program of UkraineSynaptic transmission in rat brain under altered gravity conditions.

Exposure to altered gravity environment influences many life functions of mammalian organism. The aim of this study was to investigate the effect of hypergravity on the release of glutamate and GABA from nerve terminals triggering neurotransmission process, and active neurotransmitter reuptake (affinity, kinetic properties) mediated by plasma membrane trasporters that is prominent for the termination of neurotransmission.

Selected publications (2001-2008):
1. L.G.Storchak, M.V.Linetska, N.H.Himmelreich. Okadaic acid and cyclosporin A modulate [3H]GABA release from rat brain synaptosomes. Neurochemшіstry Int. 35, 445-451, 2001

2. М.V. Linetska, L.G. Storchak, N.H. Himmelreich. Does extracellular calcium determine what pool of GABA is the target for ?-latrotoxin? Neurochemistry Int. 40, 387-395, 2002.

3. Н.Г. Гіммельрейх. a-Латротоксин як інструмент дослідження нейросекреції. Укр.біохім.журн. 74, 26-35, 2002.

4. О.Я. Шатурський, Т.М.Волкова , Н.Г. Гіммельрейх, Є.В.Грішин. Іон провідні властивості білкових пор, утворених латроінсектотоксином із отрути павука каракурта в бішарових ліпідних мембранах. Укр.біохім.журн. 74, 92, 2002.

5. Борисова Т.А., Крысанова Н.В., Гиммельрейх Н.Г. Изменение накопления L-[14C]-глутамата нервными окончаниями мозжечка и больших полушарий головного мозга крыс в условиях моделированной гипергравитации. Космическая наука и технология, 8, 101-106, 2002.

6. M.V.Linetska, L.G.Storchak, N.H.Himmelreich.?Phenylarsine oxide inhibits alpha-latrotoxin-stimulated [3H]GABA release from rat brain synaptosomes. Neurochemistry Int. 42, 583-590, 2003.

7. Borisova T., Krisanova N., Himmelreich N. Na+-dependent glutamate efflux from rat brain synaptosomes under extremal condition, Journal of Gravitational Physiology, 10, 43-44, 2003.

8. T.A.Borisova, N.V Krisanova, N.H. Himmelreich. Exposure of animals to artificial gravity conditions leads to the alteration of the glutamate release from rat cerebral hemispheres nerve terminals, Advances in Space Research, 33, 1362-1367, 2004.

9. Linetska M.V., Storchak L.G. Tarasenko A.S., Himmelreich N. H. Involvement of membrane GABA transporter in ?-latrotoxin-stimulated [3H]GABA release. Neurochemistry Int., 44, 303-312, 2004.

10. О. Трикаш, В.П. Гуменюк, В.І. Чернишов. Злиття ізольованих синаптичних везикул як модель останнього етапу регульованого екзоцитозу. Нейрофизиология, т. 36, 272-281, 2004.

11. A.S. Tarasenko, O.G. Kostrzhevska, L.G. Storchak, M.V. Linetska, T.A. Borisova and N.H. Himmelreich . Phenylarsine oxide is able to dissipate synaptic vesicle acidic pool. Neurochemistry Int. 46, 541-550, 2005.

12. Борисова Т.А., Позднякова Н.Г., Крысанова Н.В., Гиммельрейх Н.Г. ГАМК и глутамат: экзоцитоз и Nа+-зависимое освобождение из нервных окончаний головного мозга в экстремальных условиях. Космічна наука і технологія 11, 98-102, 2005.

13. Малишева М.К., Гіммельрейх Н.Г., Колчиньська Л.І.,., Цивкін В.М., Прудников І.М, Кастрикіна Т.Ф., Сторчак Л.Г., Костржевська О.Г., Тарасенко А.С., Лінецька М.В. Дослідження впливу оксиду азоту на процес нейросекреції.
Фундаментальні орієнтири науки, Київ, Академперіодика , с.130-147, 2005.

14. Т.A.Borisova, N.H. Himmelreich. Centrifuge-induced hypergravity: [3H]GABA and L-[14C]glutamate uptake, exocytosis and efflux mediated by high-affinity, sodium-dependent transporters, Advances in Space Research 36, 1340-1345, 2005.

15. Borisova Tatiana, Krisanova Natalia, Himmelreich Nina. Comparison of the еffects of DL-threo-?-benzyloxyaspartate on the glutamate release from synaptosomes before and after exposure of rats to artificial gravity. J. Grav. Physiol. 12, 23-24, 2005.

16. T.A. Borisova, N.V. Krisanova, N. H.Himmelreich: Artificial gravity loading increases the effects of the glutamate transporter inhibitors on the glutamate release and uptake in rat brain nerve terminals. Microgravity sci. technol., XVIII-3/4, 230-233, 2006

17. Borisova Tatiana & Krisanova Natalia Ground-based hypergravity simulated modeling changed the effects of the glutamate transporter inhibitor on the carrier-mediated glutamate release in low [Na +] media from rat brain nerve terminals. Journal of Gravitational Physiology, 2006, 13, 137-138.

18. Tarasenko A.S., Linetska M..V., Storchak L.G., Himmelreich N.H. Improvement of metabolic competence of isolated nerve terminals by extracellular pyruvate. Ukr. Biochim.zhurn. №5. 51-62, 2006.

19. Tarasenko A.S., Linetska M..V., Storchak L.G., Himmelreich N.H. Effectiveness of extracellular lactate/pyruvate for sustaining the synaptic vesicle proton gradient generation and vesicular accumulation of ?-aminobutyric acid . J Neurochem. 99, 787–796, 2006.

20. Trikash I., Kolchinska L. Fusion of synaptic vesicles and plasma membrane in the presense of synaptosomal soluble proteins. Neurochemistry Int. 49, 270-275, 2006.

21. Shatursky O.Ya., Volkova T.M., Romanenko O.V., Himmelreich N.H., Grishin E.V. Vitamin B1 thiazole derivative reduces transmembrane current through ionic channels formed by toxins from black widow spider venom and sea anemone in planar phospholipids membranes. Biochim. Biophys. Acta, 1768, 207-217, 2007.

22. Shatursky O.Ya., Volkova T.M., Himmelreich N.H., Grishin E.V. The geometry of the ionic channel lumen formed by a-latroinsectotoxin from black widow spider venom in the bilayer lipid membranes. Biochim. Biophys. Acta 1768, 2757-2763, 2007.

23. Vassilevski A.A., Kozlov S.A., Zhmak M.N., Kudelina I.A., Dubovski P.V., Shatursky O.Ya. , Arseniev A.S., Grishin E.V. Synthetic analogues of antimicrobial peptides from the venom of the central Asian spider Lachesana tarabaevi. Russian J. Bioorg. Chem., 33, 376-382, 2007

24. Borisova Tatiana & Kasatkina Ludmila. Glutamate transporters of blood platelets as potential peripheral markers to analyze changes of glutamate transport activity in brain under altered gravity conditions. J.Gravit. Physiol. 14, 81-82, 2007.

25.Tarasenko A.S., Storchak L.G. and Himmelreich N.H. ?-Latrotoxin affects mitochondrial potential and synaptic vesicle proton gradient of nerve terminals. Neurochemistry Int., 2, 392-400, 2008.

26. Trikash, I.O., Volynets, G.P., Remenyak, O.V., Gorchev,V.F., Docking, fusion of synaptic vesicles in cell-free model system of exocytosis. Neurochemistry Int., doi:10.1016/j.neuint.2008.09.010

Staff of the Department of Neurochemistry:

Borisova T. O., PhD, senior researcher
Parkhomenko M.T., PhD, leading researcher
Pozdnyakova N.G., PhD, researcher
Tarasenko A.S., PhD, senior researcher
Trikash I.O., PhD, senior researcher
Storchak L.G., PhD, senior researcher
Shatursky O.Ya., PhD, senior researcher
Yatsenko L.M., PhD, researcher

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