CNS and Neurological Disorders - Drug Targets

, том 21 , издание 3 , страницы 278-289

Neurokinin-1 Receptor Antagonist Reverses Functional CNS Alteration Caused by Combined γ-rays and Carbon Nuclei Irradiation

Viktor S. Kokhan ¹

Sofia Mariasina ^{2, 3}

Vladimir A. Pikalov ^{4, 5}

Д. А. Абаимов ⁶

Siva G. Somasundaram ^{7, 8}

Cecil E. Kirkland ^{7, 8}

Gjumrakch Aliev ^{9, 10}

Скрыть аффилиации авторов Показать аффилиации авторов: 10 аффилиаций

V.P. Serbsky Federal Medical Research Centre for Psychiatry and Narcology, Moscow, Russia |

Department of Biochemistry, M.V. Lomonosov Moscow State University, Moscow, Russia |

⁴

Institute for High Energy Physics A.A. Logunov of NRC “Kurchatov Institute”, Protvino, Russia |

⁵

Institute for High Energy Physics A.A. Logunov of NRC “Kurchatov Institute”, Protvino, Russia |

⁶

Research Centre of Neurology, Moscow, Russia |

⁷

Department of Biological Sciences, Salem University, Salem, WV 26426, USA |

⁸

Department of Biological Sciences, Salem University, Salem, WV 26426, USA |

⁹

I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Sechenov University, 8/2 Trubetskaya Str., Moscow 119991, Russia | Research Institute of Human Morphology,3 Tsyurupy Street, Moscow 117418, Russian Federation | Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Russia | GALLY International Research Institute, 7733 Louis Pasteur Drive, #330, San Antonio, TX 78229, USA |

¹⁰

Тип публикации: Journal Article

Дата публикации: 2022-03-01

Bentham Science Publishers Ltd.

CNS and Neurological Disorders - Drug Targets

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SJR: 0.710

CiteScore: 5.5

Impact factor: 3.0

ISSN: 18715273, 19963181

DOI: 10.2174/1871527320666210122092330

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PubMed ID: 33480350

Pharmacology

General Neuroscience

Краткое описание

Background:

Ionizing Radiation (IR) is one of the major limiting factors for human deep-space missions. Preventing IR-induced cognitive alterations in astronauts is a critical success factor. It has been shown that cognitive alterations in rodents can be inferred by alterations of a psycho- emotional balance, primarily an anxiogenic effect of IR. In our recent work, we hypothesized that the neurokinin-1 (NK1) receptor might be instrumental for such alterations.

Objective:

The NK1 receptor antagonist rolapitant and the classic anxiolytic diazepam (as a comparison drug) were selected to test this hypothesis on Wistar rats.

Method:

Pharmacological substances were administered through intragastric probes. We used a battery of tests for a comprehensive ethological analysis. High-performance liquid chromatography was applied to quantify monoamines content. An analysis of mRNA expression was performed by real-time PCR. Protein content was studied by the Western blotting technique.

Results:

Our salient finding includes no substantial changes in anxiety, locomotor activity and cognitive abilities of treated rats under irradiation. No differences were found in the content of monoamines. We discovered a synchronous effect on mRNA expression and protein content of 5- HT2a and 5-HT4 receptors in the prefrontal cortex, as well as decreased content of serotonin transporter and increased content of tryptophan hydroxylase in the hypothalamus of irradiated rats. Rolapitant affected the protein amount of a number of serotonin receptors in the amygdala of irradiated rats.

Conclusion :

Rolapitant may be the first atypical radioprotector, providing symptomatic treatment of CNS functional disorders in astronauts caused by IR.

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Kokhan V. S. et al. Neurokinin-1 Receptor Antagonist Reverses Functional CNS Alteration Caused by Combined γ-rays and Carbon Nuclei Irradiation // CNS and Neurological Disorders - Drug Targets. 2022. Vol. 21. No. 3. pp. 278-289.

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Kokhan V. S., Mariasina S., Pikalov V. A., Абаимов Д. А., Somasundaram S. G., Kirkland C. E., Aliev G. Neurokinin-1 Receptor Antagonist Reverses Functional CNS Alteration Caused by Combined γ-rays and Carbon Nuclei Irradiation // CNS and Neurological Disorders - Drug Targets. 2022. Vol. 21. No. 3. pp. 278-289.

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TY - JOUR

DO - 10.2174/1871527320666210122092330

UR - https://www.eurekaselect.com/190584/article

TI - Neurokinin-1 Receptor Antagonist Reverses Functional CNS Alteration Caused by Combined γ-rays and Carbon Nuclei Irradiation

T2 - CNS and Neurological Disorders - Drug Targets

AU - Kokhan, Viktor S.

AU - Mariasina, Sofia

AU - Pikalov, Vladimir A.

AU - Абаимов, Д. А.

AU - Somasundaram, Siva G.

AU - Kirkland, Cecil E.

AU - Aliev, Gjumrakch

PY - 2022

DA - 2022/03/01

PB - Bentham Science Publishers Ltd.

SP - 278-289

IS - 3

VL - 21

PMID - 33480350

SN - 1871-5273

SN - 1996-3181

ER -

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@article{2022_Kokhan,

author = {Viktor S. Kokhan and Sofia Mariasina and Vladimir A. Pikalov and Д. А. Абаимов and Siva G. Somasundaram and Cecil E. Kirkland and Gjumrakch Aliev},

title = {Neurokinin-1 Receptor Antagonist Reverses Functional CNS Alteration Caused by Combined γ-rays and Carbon Nuclei Irradiation},

journal = {CNS and Neurological Disorders - Drug Targets},

year = {2022},

volume = {21},

publisher = {Bentham Science Publishers Ltd.},

month = {mar},

url = {https://www.eurekaselect.com/190584/article},

number = {3},

pages = {278--289},

doi = {10.2174/1871527320666210122092330}

}

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Kokhan, Viktor S., et al. “Neurokinin-1 Receptor Antagonist Reverses Functional CNS Alteration Caused by Combined γ-rays and Carbon Nuclei Irradiation.” CNS and Neurological Disorders - Drug Targets, vol. 21, no. 3, Mar. 2022, pp. 278-289. https://www.eurekaselect.com/190584/article.