Alexei Verkhratsky

Alexei Verkhratsky, (Ukrainian: Олексій Верхратський,[3] Russian: Алексей Верхратский[4]) sometimes spelled Alexej, is a professor of neurophysiology at the University of Manchester best known for his research on the physiology and pathophysiology of neuroglia, calcium signalling, and brain ageing. He is an elected member and vice-president of Academia Europaea, of the German National Academy of Sciences Leopoldina, of the Real Academia Nacional de Farmacia (Spain), of the Slovenian Academy of Sciences and Arts, of Polish Academy of Sciences, and Dana Alliance for Brain Initiatives, among others. Since 2010. he is a Ikerbasque Research Professor and from 2012 he is deputy director of the Achucarro Basque Center for Neuroscience in Bilbao. He is a distinguished professor at Jinan University, China Medical University of Shenynag, and Chengdu University of Traditional Chinese Medicine and is an editor-in-chief of Cell Calcium, receiving editor for Cell Death and Disease, and Acta Physiologica and member of editorial board of many academic journals.

Alexei Verkhratsky
Олексій Верхратский
Born(1961-07-30)July 30, 1961[1]
Stanislaw (Ivano-Frankivsk), Galicia, Western Ukraine[2]
EducationPhD, D.Sc.
Alma materBogomoletz Institute of Physiology, Kyiv Medical Institute
Known forResearch on glial physiology and pathophysiology, calcium signalling, brain ageing
Spouse(s)Irina Verkhratska
ChildrenDina
AwardsCopernicus Gold Medal, Research Award of German Purine Club
Scientific career
FieldsNeurophysiology, neuroglia, neurones, how glia affects health and disease
InstitutionsUniversity of Manchester, Achucarro Basque Center for Neuroscience, Max-Delbrück Center of Molecular Medicine, Bogomoletz Institute of Physiology
Theses
  • Mechanisms of calcium signal generation in neurones and glial cells (1993)
  • Tetrodotoxin sensitive ionic currents in the membrane of isolated cardiomyocytes (1986)
Doctoral advisorPlaton Kostiuk

Family

Alexei is married to Irina Verkhratska and has a daughter, Dina. His father is Nestor Verkhratsky (Верхратський Нестoр Сергійович), a gerontologist who headed a laboratory at the Institute of Gerontology of the National Academy of Sciences of Ukraine.[5][6] His mother is Nina Verzykosvka (Вержиковська Ніна Василівна), who was a head of department at the same Institute. His grandfather is Sergey Verkhratsky (Верхратський Сергій Авраaмович) (ukr) who was head of the Department of Surgery in Ivano-Frankivsk National Medical University, a renowned historian of medicine, and a decorated veteran of both World Wars having received the Order of Lenin, Order of the Red Star, and Order of the Patriotic War.[7][8][9] His grandmother was Dina Shirman-Verkhratska (Ширман-Верхратська Діна Алексеевна), a well known gynaecologist.

Education

Alexei graduated from the Kyiv Medical Institute in 1983. Staying in Kyiv, he obtained a PhD under the supervision of Prof. Platon Kostyuk from the Bogomoletz Institute of Physiology in 1986 and he received a D.Sc. from the same Institute in 1993.[10][11]

Career

After completing his PhD, Alexei worked as a research scientist at the Department of General Physiology of the Nervous System, Bogomoletz Institute of Physiology for several years. In 1989, he went to Heidelberg University in the laboratory of Helmut Kettenmann, who introduced Alexei to neuroglial research. Alexei also was a guest scientist at the Research Group of Cellular Neurophysiology, Max Planck Institute for Biophysical Chemistry and the Department of Cellular Neuroscience of the Max Delbrück Center for Molecular Medicine in Germany in 1992 and 1993, respectively.

In the Ukraine, he was concurrently the Deputy director of the International Center of Molecular Physiology of the National Academy of Sciences of Ukraine and head of the Research Group of Cellular Neuroscience, Bogomoletz Institute of Physiology. He returned to Germany in 1995 as a senior research scientist at the Department of Cellular Neuroscience in the Max Delbrück Center for Molecular Medicine. Moving to the UK in 1999, he has held multiple positions at the University of Manchester including senior lecturer, reader, professor and chairman in the School of Biological Sciences.

Research

Glial physiology

In 1990, Verkhratsky discovered functional expression of low- and high-threshold Ca2+ channels in oligodendroglial precursors, this is the earliest finding underlying the concept of electrical excitability of NG2-glia.[12] When working in Berlin at the Max Delbruck Center for Molecular medicine Verkhratsky Verkhratsky and Kettenmann performed numerous seminal observation of intracellular Ca2+ signalling and defined the concept of glial Ca2+ excitability.[13] He was the first to demonstrate in situ functional expression of metabotropic purinoceptors linked to InsP3-induced Ca2+ release in oligodendroglia[14] and in cerebellar Bergmann astrocytes.[15]

After moving to Manchester, Verkhratsky focused on astroglia and characterised various aspects of astrocyte membrane physiology and regulation of glial [Ca2+]i dynamics. In particular, he discovered functional NMDA receptors in cortical astroglia, and demonstrated their synaptic activation[16] and contribution to astrocytic Ca2+ signalling triggered by neuronal activity. Subsequently, he identified a unique expression of highly ATP-sensitive P2X1/5 receptors in cortical astrocytes and characterised their role in translating neuronal synaptic activity to astroglial [Ca2+]i signalling.[17]

Verkhratsky further extended the concept of astroglial excitability as “ionic” excitability mediated by major ions, which create ionic signals coordinated in space and time; these ionic signals control the activity of astroglial homeostatic cascades and link neuronal firing and synaptic transmission to astrocyte functional responses.[18] The development of this concept begun from the very first recordings of astroglial Na+ signals in response to physiological stimulation in situ in cerebellar Bergmann radial astrocytes.[19] Subsequently, Verkhratsky analysed astroglial Na+ dynamics associated with the activity of glial glutamate transporters that are critical for glutamate clearance and glutamatergic transmission.[20] Verkhratsky found that activation of glial transporters either by exogenous glutamate or by activation of glutamatergic transmission results in large Na+ influx which generate substantial and long-lasting [Na+]i transients in processes of astrocytes. Based on these observations, he proposed a new concept astroglial Na+ signalling.[21] The concept of astroglial ionic excitability was further integrated in the theory of homeostatic astroglia[22] and is closely associated with the definition of an astroglial cradle, developed with Maiken Nedergaard,[23] that assigns to perisynaptic astrocytic processes a role of multifunctional compartment, which controls emergence, maturation, maintenance, performance and demise of synapses in the central nervous system. In a series of highly cited conceptual reviews he outlined basic principles of glial physiology and pathophysiology, which significantly influenced this rapidly developing area of neuroscience. Working with Arthur Butt, Verkhratsky published two textbooks on physiology and pathophysiology of neuroglia in 2007 and 2013 and have been the only didactic writings on neuroglia.

Cellular mechanisms of brain ageing

Verkhratsky conducted the first recordings of Ca2+ currents in aged sensory neurones in 1993.[24] He subsequently pioneered cytosolic Ca2+ recordings in aged neurones in situ, which gave direct experimental support for multiple aspects of a “Ca2+ theory of ageing”. Verkhratsky was the first to perform an in depth analysis of astrocytic structure and function in the ageing brain. He has demonstrated regional differences in astroglial morphological appearances, which ranged from cytoskeletom hypertrophy to cytoskeleton atrophy. He also found that large populations of astrocytes negative to classical marker GFAP but positive to glutamine synthetase or S100B protein do not show hypertrophic changes in the aged brain thus suggesting that brain senescence is not associated with widespread astrogliosis.[25] He also performed first detailed analysis of functional properties of glutamate transporters, glutamate and purinoceptors in old astrocytes in situ and found that brain ageing is associated with significant decrease in the density of these signalling molecules.[26]

Glial pathophysiology

Verkhratsky has developed a new concept of astroglial atrophy associated with the loss of function and glial paralysis as key elements of neuropathology; astroglial atrophy contributes to pathophysiology of several neurological diseases from neuropsychiatric disorders to neurodegeneration. First, in collaboration with Rodriguez, he discovered prominent inhibition of neurogenesis (linked to the radial astrocytes-neural stem cells) in the animal model of Alzheimer's disease.[27] Subsequently, he discovered morphological and functional evidence for astroglial atrophy at the early stages of AD that preceded the appearance of the typical neuronal histopathology in animal models;[28] these observations have been subsequently corroborated in experiments on astrocytes differentiated from pluripotent stem cells obtained from patients suffering from clinically confirmed Alzheimer's disease in both familial and sporadic forms.[29] He demonstrated deficient astrogliosis (indicative of functional atrophy) in the brain regions most vulnerable to Alzheimer-like pathology;[30] these deficits in astroglial protection can be associated with brain region-specific alterations of the Ca2+ signalling toolkit. He also found that environmental stimulation (enriched environment and physical stimulation) restored AD associated glial abnormalities.[31]

Physiology of neurones

Verkhratsky contributed to the identification of ER Ca2+ release mechanisms in neurones; he characterised in detail the caffeine-induced Ca2+ release in sensory neurones[32] and was the first to perform real-time measurements of intra-ER Ca2+ dynamics in neurones to demonstrate the graded nature of Ca2+-induced Ca2+ release.[33] Together with Denis Burdakov, he also found and characterised the link between physiological glucose changes and excitability of hypothalamic neurones.[34]

Honours and awards

Editorial commitments

Selected publications
  1. Verkhratsky, Alexei; Butt, Arthur (2007). Glial Neurobiology: A Textbook. John Wiley & Sons, Ltd. p. 232. doi:10.1002/9780470517796. ISBN 9780470015643.
  2. Verkhratsky, Alexei; Butt, Arthur (2013). Glial Physiology and Pathophysiology. John Wiley & Sons, Ltd. p. 556. doi:10.1002/9781118402061. ISBN 9780470978528.
  3. Burnstock, Geoffrey; Verkhratsky, Alexei (2012). Purinergic Signalling in the Nervous System. Springer Verlag. p. 715. ISBN 978-3-642-28863-0.
  4. Verkhratsky, Alexei; Nedergaard, Maiken (2018). "Physiology of Astroglia". Physiological Reviews. 98 (1): 239–389. doi:10.1152/physrev.00042.2016. PMC 6050349. PMID 29351512.
  5. Kettenmann, Helmut; Hanisch, Uwe-Karsten; Noda, Mami; Verkhratsky, Alexei (November 2011). "Physiology of Microglia". Physiological Reviews. American Physiological Society. 91 (2): 461–553. doi:10.1152/physrev.00011.2010. PMID 21527731.
  6. Kettenmann, Helmut; Kirchhoff, Frank; Verkhratsky, Alexei (2013). "Microglia: new roles for the synaptic stripper". Neuron. Cell Press. 77 (1): 10–18. doi:10.1016/j.neuron.2012.12.023. PMID 23312512. S2CID 7153421.
  7. Verkhratsky, Alexei (2005). "Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons". Physiological Reviews. American Physiological Society. 85 (1): 201–279. doi:10.1152/physrev.00004.2004. PMID 15618481.

See also

References
  1. "Curriculum Vitae Prof. Dr. Alexei Verkhratsky" (PDF). German National Academy of Sciences Leopoldina. Retrieved 18 August 2020.
  2. "Alexei Verkhratsky". Slovenian Academy of Sciences and Arts. Retrieved 29 July 2020.
  3. Олексій Верхратський (25 February 2005). "Лідери на задвірках, або Як вийти з найглибшої кризи, що охопила нашу академічну систему". ZN,UA (in Ukrainian). Retrieved 30 July 2020.
  4. "Верхратский Алексей". Expert.ru (in Russian). 20 July 2020. Retrieved 30 July 2020.
  5. Л. Ф. Андріанова. "Верхратський Нестір Сергійович". Encyclopedia of Modern Ukraine (in Ukrainian). Retrieved 4 August 2020.
  6. "Пішов з життя Нестор Верхратський (1931-2019)". National Academy of Medical Sciences of Ukraine (in Ukrainian). 8 July 2019. Retrieved 30 July 2020.
  7. "Верхратський Сергій Аврамович". Encyclopedia of Modern Ukraine (in Ukrainian). Retrieved 4 August 2020.
  8. "Медицинский труэнтизм как важная проблема культуры и развития общества". PetrSU (in Russian). Retrieved 4 August 2020.
  9. "Верхратский Сергей Аврамович". Info Farm (in Russian). 15 February 2016. Retrieved 4 August 2020.
  10. "Prof. A. Verkhratsky". Innovative Medicine Center. Retrieved 29 July 2020.
  11. "中国医科大学" 红医讲坛 "系列学术活动之院士高峰论坛-Alexei Verkhratsky院士讲座". Sohu (in Chinese). 3 June 2019. Retrieved 4 August 2020.
  12. Verkhratsky, Alexej N.; Trotter, J.; Kettenmann, Helmut (4 May 1990). "Cultured glial precursor cells from mouse cortex express two types of calcium currents". Neuroscience Letters. 112 (2–3): 194–198. doi:10.1016/0304-3940(90)90202-K. PMID 2163037. S2CID 42047089.
  13. Verkhratsky, Alexej; Orkand, Richard K.; Kettenmann, Helmut (1998). "Glial calcium: homeostasis and signaling function". Physiological Reviews. 78 (1): 99–141. doi:10.1152/physrev.1998.78.1.99. PMID 9457170.
  14. Kirischuk, S.; Scherer, J.; Kettenmann, H.; Verkhratsky, A. (1995). "Activation of P2-purinoreceptors triggered Ca2'release from InsP3-sensitive internal stores in mammalian". Journaal of Physiology. 483 (1): 41–57. doi:10.1113/jphysiol.1995.sp020566. PMC 1157870. PMID 7776240.
  15. Kirischuk, S.; Moller, T.; Voitenko, N.; Kettenmann, H.; Verkhratsky, A. (1 December 1995). "ATP-induced cytoplasmic calcium mobilization in Bergmann glial cells". Journal of Neuroscience. 15 (12): 7861–7871. doi:10.1523/JNEUROSCI.15-12-07861.1995. PMC 6577954. PMID 8613725. S2CID 14561085.
  16. Lalo, Ulyana; Pankratov, Yuri; Kirchhoff, Frank; North, R. Alan; Verkhratsky, Alexei (1 August 2006). "NMDA receptors mediate neuron-to-glia signaling in mouse cortical astrocytes". Journal of Neuroscience. Society for Neuroscience. 26 (10): 2673–2683. doi:10.1523/JNEUROSCI.4689-05.2006. PMC 6675155. PMID 16525046.
  17. Lalo, Ulyana; Pankratov, Yuri; Wichert, Sven P.; Rossner, Moritz J.; North, R. Alan; Kirchhoff, Frank; Verkhratsky, Alexei (21 May 2008). "P2X1 and P2X5 subunits form the functional P2X receptor in mouse cortical astrocytes". Journal of Neuroscience. Society for Neuroscience. 28 (21): 5473–5480. doi:10.1523/JNEUROSCI.1149-08.2008. PMC 3844808. PMID 18495881.
  18. Verkhratsky, Alexei; Untiet, Verena; Rose, Christine R. (7 February 2019). "Ionic signalling in astroglia beyond calcium". The Journal of Physiology. 598 (9): 1655–1670. doi:10.1113/JP277478. PMID 30734296. S2CID 73449598.
  19. Kirischuk, S.; Kettenmann, H.; Verkhratsky, A. (1997). "Na+/Ca2+ exchanger modulates kainate-triggered Ca2+ signaling in Bergmann glial cells in situ". FASEB J. 11 (7): 566–572. doi:10.1096/fasebj.11.7.9212080. PMID 9212080. S2CID 1531724.
  20. Kirischuk, Sergei; Kettenmann, Helmut; Verkhratsky, Alexei (2007). "Membrane currents and cytoplasmic sodium transients generated by glutamate transport in Bergmann glial cells". Pflugers Arch. 454 (2): 245–252. doi:10.1007/s00424-007-0207-5. PMID 17273865. S2CID 21379470.
  21. Kirischuk, Sergei; Parpura, Vladimir; Verkhratsky, Alexei (August 2012). "Sodium dynamics: another key to astroglial excitability?". Trends in Neurosciences. Elsevier Current Trends. 35 (8): 497–506. doi:10.1016/j.tins.2012.04.003. PMID 22633141. S2CID 31824.
  22. Verkhratsky, Alexei; Nedergaard, Maiken (2018). "Physiology of Astroglia". Physiological Reviews. 98 (1): 239–389. doi:10.1152/physrev.00042.2016. PMC 6050349. PMID 29351512.
  23. Nedergaard, M; Verkhratsky, A. (2012). "Artifact versus reality--how astrocytes contribute to synaptic events". Glia. 60 (7): 1013–1023. doi:10.1002/glia.22288. PMC 3340515. PMID 22228580.
  24. Kostyuk, P.; Pronchuk, N.; Savchenko, A.; Verkhratsky, A. (1 February 1993). "Calcium currents in aged rat dorsal root ganglion neurones". The Journal of Physiology. 461 (1): 467–483. doi:10.1113/jphysiol.1993.sp019523. PMC 1175267. PMID 8394426.
  25. Rodríguez, José J.; Yeh, Chia-Yu; Slavica, Terzieva; Olabarria, Markel; Kulijewicz-Nawrot, Magdalena; Verkhratsky, Alexei (January 2014). "Complex and region-specific changes in astroglial markers in the aging brain". Neurobiology of Aging. Elsevier. 35 (1): 15–23. doi:10.1016/j.neurobiolaging.2013.07.002. PMID 23969179. S2CID 22108216.
  26. Lalo, Ulyana; Palygin, Oleg; North, Richard Alan; Verkhratsky, Alexei; Pankratov, Yuriy (27 January 2011). "Age‐dependent remodelling of ionotropic signalling in cortical astroglia". Aging Cell. Blackwell Publishing Ltd. 10 (3): 392–402. doi:10.1111/j.1474-9726.2011.00682.x. PMID 21272193. S2CID 14078455.
  27. Rodríguez, José J.; Jones, Victoria C.; Masashi, Tabuchi; Allan, Stuart M.; Knight, Elysse M.; LaFerla, Frank M.; Oddo, Salvatore; Verkhratsky, Alexei (13 August 2008). "Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer's disease". PLOS ONE. Public Library of Science. 3 (8): e2935. Bibcode:2008PLoSO...3.2935R. doi:10.1371/journal.pone.0002935. PMC 2492828. PMID 18698410.
  28. Olabarria, Markel; Noristani, Harun N.; Verkhratsky, Alexei; Rodríguez, José J. (5 February 2010). "Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer's disease". Glia. 58 (7): 831–838. doi:10.1002/glia.20967. PMID 20140958. S2CID 22665630.
  29. Jones, Vicky Claire; Atkinson-Dell, Rebecca; Verkhratsky, Alexei; Mohamet, Lisa (23 March 2017). "Aberrant iPSC-derived human astrocytes in Alzheimer's disease". Cell Death & Disease. 8 (3): e2696. doi:10.1038/cddis.2017.89. PMC 5386580. PMID 28333144.
  30. Yeh, CY; Vadhwana, B.; Verkhratsky, A.; Rodriguez, JJ (2011). "Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease". ASN Neuro. 3 (5): 271–279. doi:10.1042/AN20110025. PMC 3243908. PMID 22103264. S2CID 1043017.
  31. Rodriguez, JJ; Terzieva, S.; Olabarria, M.; Lanza, RG; Verkhratsky, A. (2013). "Enriched environment and physical activity reverse astrogliodegeneration in the hippocampus of AD transgenic mice". Cell Death Dis. 4 (6): e678. doi:10.1038/cddis.2013.194. PMC 3702309. PMID 23788035.
  32. Usachev, Y.; Shmigol, A.; Pronchuk, N.; Kostyuk, P.; Verkhratsky, A. (1993). "Caffeine-induced calcium release from internal stores in cultured rat sensory neurons". Neuroscience. 57 (3): 845–859. doi:10.1016/0306-4522(93)90029-F. PMID 8309540. S2CID 24276265.
  33. Solovyova, N.; Veselovsky, N.; Toescu, E. C.; Verkhratsky, A. (2002). "Ca2+ dynamics in the lumen of the endoplasmic reticulum in sensory neurons: direct visualization of Ca2+-induced Ca2+ release triggered by physiological Ca2+ entry". EMBO J. 21 (4): 622–630. doi:10.1093/emboj/21.4.622. PMC 125857. PMID 11847110.
  34. Burdakov, D.; Gerasimenko, O.; Verkhratsky, A. (2005). "Physiological changes in glucose differentially modulate the excitability of hypothalamic MCH and orexin neurons in situ". Journal of Neuroscience. 25 (9): 2429–2433. doi:10.1523/JNEUROSCI.4925-04.2005. PMC 6726089. PMID 15745970. S2CID 18796484.
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  39. "老年慢性重大疾病药学学术大会暨第七届广东省药学会老年药学专业委员会2019学术年会在广州召开". GuangDong Pharmaceutical Association (in Chinese). 24 December 2019. Retrieved 4 August 2020.
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