Mechanism of action of the new ethanolamine derivative bis{2-[(2E)-4-hydroxy-4-oxobut-2-enoyloxy]-N,N-diethylethanaminium}butanedioate

Yu I. Sysoev, E. A. Popugaeva, D. P. Chernyuk, I. A. Titovich, E. V. Zagladkina, V. C. Bolotova, Ilya Bezprozvanny, S. V. Okovityi

Research output: Contribution to journalArticle

Abstract

The mechanism of neuroprotective action of a new ethanolamine derivative, bis{2-[(2E)-4-hydroxy-4-oxobut-2-enoyloxy]-N,N-diethylethanaminium}butane-dioate (FDES), was studied by means of dendritic spines visualization in a confocal microscope, calcium imaging in postsynaptic dendritic spines, and knockdown of protein expression in primary mice hippocampal cells culture by RNA interference. It was established that a possible mechanism of FDES action is related to the activation of neuronal store-operated calcium entry (nSOCE) into postsynaptic dendritic spines. During knockdown of the TRPC6 channels (the main regulators of hippocampal SOCE), the hippocampal culture FDES did not activate calcium entry into hippocampal neurons, which indicated the specificity of FDES action on nSOCE. On the model of cerebral ischemia, FDES in comparison to reference agents (citicoline and cytoflavin) improved short-term memory of rats in the Barnes maze test (reduced the number of errors by 71%, p = 0.0023) with respect to data received 24 h before the test. In the nanomolar dose range, FDES was found to demonstrate neuroprotective properties in primary hippocampal culture, as manifested in the ability to protect mushroom spines from amyloid synaptotoxicity by 15% (p ≤ 0.0001), which resulted in stabilizing and enhancing synaptic transmission. The obtained results indicate that FDES is of interest for further investigation as a neuroprotective agent.

Original languageEnglish (US)
Pages (from-to)3-10
Number of pages8
JournalEksperimental'naya i Klinicheskaya Farmakologiya
Volume82
Issue number4
DOIs
StatePublished - Jan 1 2019

Fingerprint

Ethanolamine
Dendritic Spines
Calcium
Derivatives
Cytidine Diphosphate Choline
Aptitude
Agaricales
Neuroprotective Agents
RNA Interference
Brain Ischemia
Short-Term Memory
Cell culture
Amyloid
Synaptic Transmission
Neurons
Rats
Spine
Microscopes
Visualization
Cell Culture Techniques

Keywords

  • Cell culture
  • Citicoline
  • Cytoflavin
  • Dendritic spines
  • Ethanolamine derivative
  • Memory
  • Neuroprotection
  • Rats

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Mechanism of action of the new ethanolamine derivative bis{2-[(2E)-4-hydroxy-4-oxobut-2-enoyloxy]-N,N-diethylethanaminium}butanedioate. / Sysoev, Yu I.; Popugaeva, E. A.; Chernyuk, D. P.; Titovich, I. A.; Zagladkina, E. V.; Bolotova, V. C.; Bezprozvanny, Ilya; Okovityi, S. V.

In: Eksperimental'naya i Klinicheskaya Farmakologiya, Vol. 82, No. 4, 01.01.2019, p. 3-10.

Research output: Contribution to journalArticle

Sysoev, Yu I. ; Popugaeva, E. A. ; Chernyuk, D. P. ; Titovich, I. A. ; Zagladkina, E. V. ; Bolotova, V. C. ; Bezprozvanny, Ilya ; Okovityi, S. V. / Mechanism of action of the new ethanolamine derivative bis{2-[(2E)-4-hydroxy-4-oxobut-2-enoyloxy]-N,N-diethylethanaminium}butanedioate. In: Eksperimental'naya i Klinicheskaya Farmakologiya. 2019 ; Vol. 82, No. 4. pp. 3-10.
@article{f075f335a27b49869d7d35e51b4cacf0,
title = "Mechanism of action of the new ethanolamine derivative bis{2-[(2E)-4-hydroxy-4-oxobut-2-enoyloxy]-N,N-diethylethanaminium}butanedioate",
abstract = "The mechanism of neuroprotective action of a new ethanolamine derivative, bis{2-[(2E)-4-hydroxy-4-oxobut-2-enoyloxy]-N,N-diethylethanaminium}butane-dioate (FDES), was studied by means of dendritic spines visualization in a confocal microscope, calcium imaging in postsynaptic dendritic spines, and knockdown of protein expression in primary mice hippocampal cells culture by RNA interference. It was established that a possible mechanism of FDES action is related to the activation of neuronal store-operated calcium entry (nSOCE) into postsynaptic dendritic spines. During knockdown of the TRPC6 channels (the main regulators of hippocampal SOCE), the hippocampal culture FDES did not activate calcium entry into hippocampal neurons, which indicated the specificity of FDES action on nSOCE. On the model of cerebral ischemia, FDES in comparison to reference agents (citicoline and cytoflavin) improved short-term memory of rats in the Barnes maze test (reduced the number of errors by 71{\%}, p = 0.0023) with respect to data received 24 h before the test. In the nanomolar dose range, FDES was found to demonstrate neuroprotective properties in primary hippocampal culture, as manifested in the ability to protect mushroom spines from amyloid synaptotoxicity by 15{\%} (p ≤ 0.0001), which resulted in stabilizing and enhancing synaptic transmission. The obtained results indicate that FDES is of interest for further investigation as a neuroprotective agent.",
keywords = "Cell culture, Citicoline, Cytoflavin, Dendritic spines, Ethanolamine derivative, Memory, Neuroprotection, Rats",
author = "Sysoev, {Yu I.} and Popugaeva, {E. A.} and Chernyuk, {D. P.} and Titovich, {I. A.} and Zagladkina, {E. V.} and Bolotova, {V. C.} and Ilya Bezprozvanny and Okovityi, {S. V.}",
year = "2019",
month = "1",
day = "1",
doi = "10.30906/0869-2092-2019-82-4-3-10",
language = "English (US)",
volume = "82",
pages = "3--10",
journal = "Eksperimental'naya i Klinicheskaya Farmakologiya",
issn = "0869-2092",
publisher = "Izdatelstvo Meditsina",
number = "4",

}

TY - JOUR

T1 - Mechanism of action of the new ethanolamine derivative bis{2-[(2E)-4-hydroxy-4-oxobut-2-enoyloxy]-N,N-diethylethanaminium}butanedioate

AU - Sysoev, Yu I.

AU - Popugaeva, E. A.

AU - Chernyuk, D. P.

AU - Titovich, I. A.

AU - Zagladkina, E. V.

AU - Bolotova, V. C.

AU - Bezprozvanny, Ilya

AU - Okovityi, S. V.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The mechanism of neuroprotective action of a new ethanolamine derivative, bis{2-[(2E)-4-hydroxy-4-oxobut-2-enoyloxy]-N,N-diethylethanaminium}butane-dioate (FDES), was studied by means of dendritic spines visualization in a confocal microscope, calcium imaging in postsynaptic dendritic spines, and knockdown of protein expression in primary mice hippocampal cells culture by RNA interference. It was established that a possible mechanism of FDES action is related to the activation of neuronal store-operated calcium entry (nSOCE) into postsynaptic dendritic spines. During knockdown of the TRPC6 channels (the main regulators of hippocampal SOCE), the hippocampal culture FDES did not activate calcium entry into hippocampal neurons, which indicated the specificity of FDES action on nSOCE. On the model of cerebral ischemia, FDES in comparison to reference agents (citicoline and cytoflavin) improved short-term memory of rats in the Barnes maze test (reduced the number of errors by 71%, p = 0.0023) with respect to data received 24 h before the test. In the nanomolar dose range, FDES was found to demonstrate neuroprotective properties in primary hippocampal culture, as manifested in the ability to protect mushroom spines from amyloid synaptotoxicity by 15% (p ≤ 0.0001), which resulted in stabilizing and enhancing synaptic transmission. The obtained results indicate that FDES is of interest for further investigation as a neuroprotective agent.

AB - The mechanism of neuroprotective action of a new ethanolamine derivative, bis{2-[(2E)-4-hydroxy-4-oxobut-2-enoyloxy]-N,N-diethylethanaminium}butane-dioate (FDES), was studied by means of dendritic spines visualization in a confocal microscope, calcium imaging in postsynaptic dendritic spines, and knockdown of protein expression in primary mice hippocampal cells culture by RNA interference. It was established that a possible mechanism of FDES action is related to the activation of neuronal store-operated calcium entry (nSOCE) into postsynaptic dendritic spines. During knockdown of the TRPC6 channels (the main regulators of hippocampal SOCE), the hippocampal culture FDES did not activate calcium entry into hippocampal neurons, which indicated the specificity of FDES action on nSOCE. On the model of cerebral ischemia, FDES in comparison to reference agents (citicoline and cytoflavin) improved short-term memory of rats in the Barnes maze test (reduced the number of errors by 71%, p = 0.0023) with respect to data received 24 h before the test. In the nanomolar dose range, FDES was found to demonstrate neuroprotective properties in primary hippocampal culture, as manifested in the ability to protect mushroom spines from amyloid synaptotoxicity by 15% (p ≤ 0.0001), which resulted in stabilizing and enhancing synaptic transmission. The obtained results indicate that FDES is of interest for further investigation as a neuroprotective agent.

KW - Cell culture

KW - Citicoline

KW - Cytoflavin

KW - Dendritic spines

KW - Ethanolamine derivative

KW - Memory

KW - Neuroprotection

KW - Rats

UR - http://www.scopus.com/inward/record.url?scp=85070776276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070776276&partnerID=8YFLogxK

U2 - 10.30906/0869-2092-2019-82-4-3-10

DO - 10.30906/0869-2092-2019-82-4-3-10

M3 - Article

VL - 82

SP - 3

EP - 10

JO - Eksperimental'naya i Klinicheskaya Farmakologiya

JF - Eksperimental'naya i Klinicheskaya Farmakologiya

SN - 0869-2092

IS - 4

ER -