c-fos, ERK1 / 2, MAP2, NOTCH1 proteins expression patterns in human cerebral cortex neurons after ischemic stroke

  • Authors: Sergeeva S.1, Lyundup A.V.1, Beregovykh V.V.1, Savin A.A.2, Litvitskiy P.F.1, Gorbacheva L.R.3, Kiseleva E.V.4, Breslavich I.D.3, Kutsenko K.I.5,6, Shishkina L.V.7
  • Affiliations:
    1. I.M. Sechenov First Moscow State Medical University (Sechenov University)
    2. A.I. Yevdokimov Moscow State University of Medicine and Dentistry
    3. Lomonosov Moscow State University
    4. Koltzov Institute of Developmental Biology of Russian Academy of Sciences
    5. Bureau of Forensic Medicine of Moscow Healthcare Department
    6. Educational Private Institution of Higher Education «International Legal Institute»
    7. N.N. Burdenko Scientific Research Neurosurgery
  • URL: https://vestnikramn.spr-journal.ru/jour/article/view/1295
  • DOI: https://doi.org/10.15690/vramn1295
Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Abstract


Background: the search for protein (these include c-fos, ERK1 / 2, MAP2, NOTCH1) expression that provide neuroplasticity mechanisms of the cerebral cortex after ischemic stroke (IS) patterns is an urgent task.

Aims: to reveal c-fos, ERK1 / 2, MAP2, NOTCH1 proteins expression patterns in human cerebral cortex neurons after IS.

Materials and methods: We studied 9 left middle cerebral artery (LMCA) IS patients cerebral cortex samples from 3 zones: 1 - the zone adjacent to the necrotic tissue focus; 2 - zone remote from the previous one by 4 - 7 cm; 3 - zone of the contralateral hemisphere, symmetric to the IS focus. Control samples were obtained from 3 accident died people. Identification of targeted proteins NSE, c-fos, ERK1 / 2, MAP2, NOTCH1 was performed by indirect immunoperoxidase immunohistochemical method.

Results: moving away from the ischemic focus, there is an increase in the density of neurons and a decrease in the damaged neurons proportion, the largest share of c-fos protein positive neurons in zone 2, NOTCH1 positive neurons in zone 1, smaller fractions of ERK1 / 2 and MAP2 positive neurons compared to the control only in samples of zone 1.

Conclusions: With the IS development, the contralateral hemisphere is intact tissue increased activation zone, while the zones 1 and 2 have pathological activation signs. In zone 1 of the range, the adaptive response of the tissue decreases, and in zone 2 it expands. Therefore, a key target for therapeutic intervention is zone 2.


Full Text

About the authors

Svetlana Sergeeva

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: svetlanapalna@mail.ru
ORCID iD: 0000-0002-0083-1213
SPIN-code: 4257-9498

Russian Federation, 8 Trubetskaya street, 119991, Moscow, Russia

кандидат медицинских наук, доцент кафедры патофизиологии

Aleksey V. Lyundup

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: lyundup@gmail.com
ORCID iD: 0000-0002-0102-5491
SPIN-code: 4954-3004

Russian Federation, 8 bld 2, Trubetskaya street, 119991 Moscow

MD, PhD

Valery V. Beregovykh

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: beregovykh@ramn.ru
ORCID iD: 0000-0002-0210-4570
SPIN-code: 5940-7554

Russian Federation, 8 Trubetskaya street, 119991, Moscow, Russia

академик РАН, доктор технических наук, профессор кафедры промышленной фармации

Aleksey A. Savin

A.I. Yevdokimov Moscow State University of Medicine and Dentistry

Email: lasavin@mail.ru
ORCID iD: 0000-0002-6340-8623
SPIN-code: 9162-6720

Russian Federation

Petr F. Litvitskiy

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: litvicki@mma.ru
ORCID iD: 0000-0003-0151-9114
SPIN-code: 6657-5937

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD, PhD, Professor

Liubov R. Gorbacheva

Lomonosov Moscow State University

Email: gorbacheva@mail.bio.msu.ru
ORCID iD: 0000-0002-3910-8831
SPIN-code: 4394-0575

Russian Federation

Ekaterina V. Kiseleva

Koltzov Institute of Developmental Biology of Russian Academy of Sciences

Email: evkiseleva@mail.ru
ORCID iD: 0000-0002-2270-6595
SPIN-code: 7421-8496

Russian Federation

Ilya D. Breslavich

Lomonosov Moscow State University

Email: br_i@inbox.ru
ORCID iD: 0000-0002-9321-9102
SPIN-code: 9615-9237

Russian Federation

Kirill I. Kutsenko

Bureau of Forensic Medicine of Moscow Healthcare Department;
Educational Private Institution of Higher Education «International Legal Institute»

Email: ceamler@gmail.com
ORCID iD: 0000-0001-9299-5153
SPIN-code: 8964-3717

Russian Federation

Lyudmila V. Shishkina

N.N. Burdenko Scientific Research Neurosurgery

Email: lshishkina@nsi.ru
ORCID iD: 0000-0001-7045-7223
SPIN-code: 6341-2050

Russian Federation

References

  • Литература
  • Pool E. M., Leimbach M., Binder E. et al. Network dynamics engaged in the modulation of motor behavior in stroke patients. Human brain mapping. 2018; 39 (3):1078-1092. doi: 10.1002/hbm.23872.
  • Kim D.H., Lee H.E., Kwon K.J. et al. Early immature neuronal death initiates cerebral ischemia-induced neurogenesis in the dentate gyrus. Neuroscience. 2015; 284:42-54. doi: 10.1016/j.neuroscience.2014.09.074.
  • Schuldiner O., Yaron A. Mechanisms of developmental neurite pruning. Cellular and Molecular Life Sciences. 2015; 72(1):101-119. doi: 10.1007/s00018-014-1729-6.
  • Maor-Nof M., Yaron A. Neurite pruning and neuronal cell death: spatial regulation of shared destruction programs. Current opinion in neurobiology. 2013;23(6):990-996. doi: 10.1016/j.conb.2013.06.007.
  • Шерстнев В.В., Юрасов В.В., Сторожева З.И. и др. Нейрогенез и апоптоз в зрелом мозге при формировании и упрочении долговременной памяти // Нейрохимия. – 2010. – Т. 27. – №2. – С. 130-137. [Sherstnev V.V., Yurasov V.V., Storozheva Z.I. et al. Neurogenesis and apoptosis in the mature brain during formation and consolidation of long-term memory. Neurochemical Journal. 2010;4(2):109-115]
  • Авдеев Д. Б., Акулинин В. А., Степанов А. С. и др. Плейотропные ферменты апоптоза и синаптическая пластичность гиппокампа белых крыс после окклюзии общих сонных артерий // Сибирский медицинский журнал. – 2018. – Т.33. – №3. – С. 102-110. doi: 10.29001/2073-8552-2018-33-3-102-110. [Avdeev D.V., Akulinin V.A., Stepanov A.S. et al. Pleiotropic enzymes of apoptosis and synaptic plasticity in albino rat hippocampus after occlusion of common carotid arteries. The Siberian Medical Journal. 2018;33(3):102-110. (In Russ.) doi: 10.29001/2073-8552-2018-33-3-102-110].
  • Roux P.P., Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 2004; 68: 320–344. doi: 10.1128/mmbr.68.2.320-344.2004.
  • Pernet V., Hauswirth W. W., Di Polo A. Extracellular signal-regulated kinase 1/2 mediates survival, but not axon regeneration, of adult injured central nervous system neurons in vivo. Journal of neurochemistry. 2005;93(1):72-83. doi: 10.1111/j.1471-4159.2005.03002.x.
  • Kim S. Y., Han Y. M., Oh M. et al. DUSP4 regulates neuronal differentiation and calcium homeostasis by modulating ERK1/2 phosphorylation. Stem cells and development. 2014;24(6):686-700. doi: 10.1089/scd.2014.0434.
  • Kaczmarek L. From c-Fos to MMP-9: In control of synaptic plasticity to produce healthy and diseased mind, a personal view. Postepy biochemii. 2018;64(2):101-109. doi: 10.18388/pb.2018_119.
  • Gao Y. J., Ji R. R. c-Fos and pERK, which is a better marker for neuronal activation and central sensitization after noxious stimulation and tissue injury? The open pain journal. 2009;2:11-17. doi: 10.2174/1876386300902010011.
  • Liu W., Wu W., Lin G. et al. Physical exercise promotes proliferation and differentiation of endogenous neural stem cells via ERK in rats with cerebral infarction. Molecular medicine reports. 2018;18(2):1455-64. doi: 10.3892/mmr.2018.9147.
  • Xiao P., Liu X. W., Zhao N. N. et al. Correlations of neuronal apoptosis with expressions of c-Fos and c-Jun in rats with post-ischemic reconditioning damage. European review for medical and pharmacological sciences. 2018;22(9):2832-2838. doi: 10.26355/eurrev_201805_14984.
  • Samandari H., Nabavizadeh F., Ashabi G. Age-related difference in protective effect of early post-conditioning on ischemic brain injury: possible involvement of MAP-2/Synaptophysin role. Metabolic brain disease. 2019;34(6):1771-80. doi: 10.1007/s11011-019-00484-3.
  • Tu M., Zhu P., Hu S. et al. Notch1 signaling activation contributes to adult hippocampal neurogenesis following traumatic brain injury. Medical science monitor: international medical journal of experimental and clinical research. 2017;23:5480. doi: 10.12659/MSM.907160.
  • Zhang X., Yang C., Gao J. et al. Voluntary running-enhanced synaptic plasticity, learning and memory are mediated by Notch1 signal pathway in C57BL mice. Brain Structure and Function. 2018;223(2):749-67. doi: 10.1007/s00429-017-1521-0.
  • Меркулов Г. А. Курс патологогистологической техники. – СПб: Медгиз, 1961. – 340 с. [Merkulov G. A. Course of histopathological technology. St. Petersburg: Medgiz; 1961. 340 p. (In Russ).]
  • Саркисов Д. С., Перов Ю. Л., Лысенко Л. В. Микроскопическая техника. – М.: Медицина, 1996. [Sarkisov D. S., Perov Yu. L., Lysenko L. V. Microscopic technology. M.: Medicine; 1996. (In Russ).]
  • Мальков П.Г., Франк Г.А., Москвина Л.В. и др. Основы обеспечения качества в гистологической лабораторной технике. Руководство / Под. ред. П.Г. Малькова, Г.А. Франка. – М.: У Никитских ворот, 2011. – 108 с. [Malkov P.G., Frank G.A., Moskvina L.V. et al. Fundamentals of quality assurance in histological laboratory technology. Leadership / Under. ed. P.G. Malkova, G.A. Franka. M.: U nikitskih vorot; 2011. 108 p.]
  • Мыцик А. В., Акулинин В. А., Степанов С. С., Ларионов П. М. Влияние ишемии на нейроглиальные взаимоотношения лобной коры большого мозга человека // Омский научный вестник. – 2013. – №1(118). – С.74-77. [Mytsik A.V., Akulinin V.A., Stepanov S.S., Larionov P.M. Ischemia influence of the neuroglial relations of frontal cortex of the human brain. Omskiy Nauchniy vestnik. 2013;1(118):74-77 (In Russ).]
  • Мыцик А. В. Использование программы ImageJ для автоматической морфометрии в гистологических исследованиях // Омский научный вестник. – 2011. – №2(100). – С. 187-189 [Mytsik А.V. Using ImageJ software application for automated morphometry of histological studies. Omskiy Nauchniy vestnik. 2011;2(100):187-189 (In Russ).]
  • McDowell J. J. Behavioral and neural Darwinism: Selectionist function and mechanism in adaptive behavior dynamics. Behavioural Processes. 2010;84(1):358-365. doi: 10.1016/j.beproc.2009.11.011.
  • Leigh R., Knutsson L., Zhou J., van Zijl P. C. Imaging the physiological evolution of the ischemic penumbra in acute ischemic stroke. Journal of Cerebral Blood Flow & Metabolism. 2018;38(9):1500-1516. doi: 10.1177/0271678X17700913.
  • Cunha R.A. How does adenosine control neuronal dysfunction and neurodegeneration?. Journal of neurochemistry. 2016;139(6):1019-55. doi: 10.1111/jnc.13724.
  • Neyazi B., Schwabe K., Alam M. et al. Neuronal expression of c-Fos after epicortical and intracortical electric stimulation of the primary visual cortex. Journal of chemical neuroanatomy. 2016;77:121-128. doi: 10.1016/j.jchemneu.2016.06.004.
  • Chen X., Shen J., Wang Y. et al. Up-regulation of c-Fos associated with neuronal apoptosis following intracerebral hemorrhage. Cellular and molecular neurobiology. 2015;35(3):363-76. doi: 10.1007/s10571-014-0132-z.

Statistics

Views

Abstract - 17

PDF (Russian) - 0

PDF (Russian) - 0

PlumX

Dimensions



Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies