ALTERATIONS IN THE EXPRESSION OF DOPAMINE CATABOLISM GENES IN DAT-KO RATS WITH INDUCED VALPROATE SYNDROME



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Abstract

Background. Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are complex disorders of nervous development. Both diseases are diagnosed in childhood and are often comorbital. Rats with a knockout of the dopamine transporter gene (DAT) exhibit symptoms characteristic of ADHD. Prenatal treatment with valproic acid (VPA) is used to model ASD. Dysfunction of the dopaminergic system may be one of the causes of ADHD and ASD. However the neurochemical mechanisms underlying dysfunction of the dopaminergic system and contributing to the pathogenesis of ADHD require further studies. Therefore, the aim of the work was to investigate the expression levels of dopamine catabolism genes in heterozygous rats with a knockout of the DAT encoding gene and induced valproate syndrome.

Materials and methods. The work was performed on 32 rats aged 40 days (adolescence). In total, 4 groups of baby rats were formed in the study - (DAT:Salt), (DAT:VPA), (WT:VPA) and (WT:Salt), where DAT/WT is the presence or absence of a genetic factor (DAT is a heterozygote for knockout of the SLC6A3 gene, WT is the wild type), VPA/Salt is the presence or absence of a toxic factor (induced valproate syndrome).

Results. The expression of mRNA monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in the midbrain was reduced in the groups (DAT:Sat), (DAT:VPA), (WT:VPA) compared to the control group (WT:Salt). The expression mRNA of catechol-O-methyltransferase (COMT) mRNA in the midbrain of rats (DAT:Salt) is significantly higher than in the control group (WT:Salt), however, the treatment with VPA leads to a decrease in COMT expression in heterozygous rats by knocking out the SLC6A3 gene. No changes in the expression of MAO-A, MAO-B, COMT mRNA were observed in the prefrontal cortex and striatum.  

Conclusion. The development of valproate syndrome and/or reduce dopamine reuptake leads to a decrease in the levels of monoamine oxidase A and monoamine oxidase B mRNA in the rat midbrain. Prenatal exposure to VPA led to a decrease in the level of COMT mRNA in the midbrain of heterozygous rats by knockout of the DAT gene.

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About the authors

I R Nazarov

Санкт-Петербургский государственный университет

Author for correspondence.
Email: inazarovgm@gmail.com
ORCID iD: 0009-0003-3789-0836
Russian Federation, 199034, Россия, Санкт-Петербург, Университетская набережная, д. 7/9

D A Obukhova

ФГБНУ "Институт экспериментальной медицины"; Санкт-Петербургский государственный университет

Email: obuhowadaria@gmail.com
ORCID iD: 0009-0002-4287-0808

Физиологический отдел им. И.П. Павлова, лаборатория нейрохимии; Биологический факультет, кафедра биохимии

197022, Россия, Санкт-Петербург, ул. Академика Павлова, 12; 199034, Россия, Санкт-Петербург, Университетская набережная, д. 7/9

V M Kudrinskaya

ФГБНУ "Институт экспериментальной медицины"; Санкт-Петербургский Политехнический Университет Петра Великого

Email: v.kudrinskaja2011@yandex.ru
ORCID iD: 0000-0002-2763-5191

Физиологический отдел им. И.П. Павлова, лаборатория нейрохимии; Институт биомедицинских систем и биотехнологий

197022, Россия, Санкт-Петербург, ул. Академика Павлова, 12; 195251, Россия, Санкт-Петербург, ул. Политехническая, 29.

N S Pestereva

ФГБНУ "Институт экспериментальной медицины"

Email: pesterevans@yandex.ru
ORCID iD: 0000-0002-3104-8790
197022, Россия, Санкт-Петербург, ул. Академика Павлова, 12

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