Dopamine receptors and key elements of the neurotrophins (BDNF, CDNF) expression patterns during critical periods of ontogenesis in the brain structures of mice with autism-like behavior (BTBR) or its absence (С57BL/6J)

Analysis of the mechanisms underlying autism spectrum disorder (ASD) is an urgent task due to the everincreasing prevalence of this condition. The study of critical periods of neuroontogenesis is of interest, since the manifestation of ASD is often associated with prenatal disorders of the brain dev...

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Main Authors: P. D. Pravikova, M. A. Arssan, E. A. Zalivina, E. M. Kondaurova, E. A. Kulikova, I. I. Belokopytova, V. S. Naumenko
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2024-07-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/4183
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author P. D. Pravikova
M. A. Arssan
E. A. Zalivina
E. M. Kondaurova
E. A. Kulikova
I. I. Belokopytova
V. S. Naumenko
author_facet P. D. Pravikova
M. A. Arssan
E. A. Zalivina
E. M. Kondaurova
E. A. Kulikova
I. I. Belokopytova
V. S. Naumenko
author_sort P. D. Pravikova
collection DOAJ
description Analysis of the mechanisms underlying autism spectrum disorder (ASD) is an urgent task due to the everincreasing prevalence of this condition. The study of critical periods of neuroontogenesis is of interest, since the manifestation of ASD is often associated with prenatal disorders of the brain development. One of the currently promising hypotheses postulates a connection between the pathogenesis of ASD and the dysfunction of neurotransmitters and neurotrophins. In this study, we investigated the expression of key dopamine receptors (Drd1, Drd2), brain-derived neurotrophic factor (Bdnf), its receptors (Ntrkb2, Ngfr) and the transcription factor Creb1 that mediates BDNF action, as well as cerebral dopamine neurotrophic factor (Cdnf) during the critical periods of embryogenesis (e14 and e18) and postnatal development (p14, p28, p60) in the hippocampus and frontal cortex of BTBR mice with autism-like behavior compared to the neurotypical C57BL/6 J strain. In BTBR embryos, on the 14th day of prenatal development, an increase in the expression of the Ngfr gene encoding the p75NTR receptor, which may lead to the activation of apoptosis, was found in the hippocampus and frontal cortex. A decrease in the expression of Cdnf, Bdnf and its receptor Ntrkb2, as well as dopamine receptors (Drd1, Drd2) was detected in BTBR mice in the postnatal period of ontogenesis mainly in the frontal cortex, while in the hippocampus of mature mice (p60), only a decrease in the Drd2 mRNA level was revealed. The obtained results suggest that the decrease in the expression levels of CDNF, BDNF-TrkB and dopamine receptors in the frontal cortex in the postnatal period can lead to significant changes in both the morphology of neurons and dopamine neurotransmission in cortical brain structures. At the same time, the increase in p75NTR receptor gene expression observed on the 14th day of embryogenesis, crucial for hippocampus and frontal cortex development, may have direct relevance to the manifestation of early autism.
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spelling doaj-art-47fe0127efc5451895969b1595aafc992025-02-01T09:58:13ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592024-07-0128440741510.18699/vjgb-24-461475Dopamine receptors and key elements of the neurotrophins (BDNF, CDNF) expression patterns during critical periods of ontogenesis in the brain structures of mice with autism-like behavior (BTBR) or its absence (С57BL/6J)P. D. Pravikova0M. A. Arssan1E. A. Zalivina2E. M. Kondaurova3E. A. Kulikova4I. I. Belokopytova5V. S. Naumenko6Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesAnalysis of the mechanisms underlying autism spectrum disorder (ASD) is an urgent task due to the everincreasing prevalence of this condition. The study of critical periods of neuroontogenesis is of interest, since the manifestation of ASD is often associated with prenatal disorders of the brain development. One of the currently promising hypotheses postulates a connection between the pathogenesis of ASD and the dysfunction of neurotransmitters and neurotrophins. In this study, we investigated the expression of key dopamine receptors (Drd1, Drd2), brain-derived neurotrophic factor (Bdnf), its receptors (Ntrkb2, Ngfr) and the transcription factor Creb1 that mediates BDNF action, as well as cerebral dopamine neurotrophic factor (Cdnf) during the critical periods of embryogenesis (e14 and e18) and postnatal development (p14, p28, p60) in the hippocampus and frontal cortex of BTBR mice with autism-like behavior compared to the neurotypical C57BL/6 J strain. In BTBR embryos, on the 14th day of prenatal development, an increase in the expression of the Ngfr gene encoding the p75NTR receptor, which may lead to the activation of apoptosis, was found in the hippocampus and frontal cortex. A decrease in the expression of Cdnf, Bdnf and its receptor Ntrkb2, as well as dopamine receptors (Drd1, Drd2) was detected in BTBR mice in the postnatal period of ontogenesis mainly in the frontal cortex, while in the hippocampus of mature mice (p60), only a decrease in the Drd2 mRNA level was revealed. The obtained results suggest that the decrease in the expression levels of CDNF, BDNF-TrkB and dopamine receptors in the frontal cortex in the postnatal period can lead to significant changes in both the morphology of neurons and dopamine neurotransmission in cortical brain structures. At the same time, the increase in p75NTR receptor gene expression observed on the 14th day of embryogenesis, crucial for hippocampus and frontal cortex development, may have direct relevance to the manifestation of early autism.https://vavilov.elpub.ru/jour/article/view/4183autismbtbr and с57bl/6 j micebdnfcdnfdopamine receptorsontogenesishippocampusfrontal cortex
spellingShingle P. D. Pravikova
M. A. Arssan
E. A. Zalivina
E. M. Kondaurova
E. A. Kulikova
I. I. Belokopytova
V. S. Naumenko
Dopamine receptors and key elements of the neurotrophins (BDNF, CDNF) expression patterns during critical periods of ontogenesis in the brain structures of mice with autism-like behavior (BTBR) or its absence (С57BL/6J)
Вавиловский журнал генетики и селекции
autism
btbr and с57bl/6 j mice
bdnf
cdnf
dopamine receptors
ontogenesis
hippocampus
frontal cortex
title Dopamine receptors and key elements of the neurotrophins (BDNF, CDNF) expression patterns during critical periods of ontogenesis in the brain structures of mice with autism-like behavior (BTBR) or its absence (С57BL/6J)
title_full Dopamine receptors and key elements of the neurotrophins (BDNF, CDNF) expression patterns during critical periods of ontogenesis in the brain structures of mice with autism-like behavior (BTBR) or its absence (С57BL/6J)
title_fullStr Dopamine receptors and key elements of the neurotrophins (BDNF, CDNF) expression patterns during critical periods of ontogenesis in the brain structures of mice with autism-like behavior (BTBR) or its absence (С57BL/6J)
title_full_unstemmed Dopamine receptors and key elements of the neurotrophins (BDNF, CDNF) expression patterns during critical periods of ontogenesis in the brain structures of mice with autism-like behavior (BTBR) or its absence (С57BL/6J)
title_short Dopamine receptors and key elements of the neurotrophins (BDNF, CDNF) expression patterns during critical periods of ontogenesis in the brain structures of mice with autism-like behavior (BTBR) or its absence (С57BL/6J)
title_sort dopamine receptors and key elements of the neurotrophins bdnf cdnf expression patterns during critical periods of ontogenesis in the brain structures of mice with autism like behavior btbr or its absence с57bl 6j
topic autism
btbr and с57bl/6 j mice
bdnf
cdnf
dopamine receptors
ontogenesis
hippocampus
frontal cortex
url https://vavilov.elpub.ru/jour/article/view/4183
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