Myelination deficiency in rats with genetically determined dopamine metabolism disorder

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Abstract

BACKGROUND: Attention deficit hyperactivity disorder is one of the most common neuropsychiatric disorders affecting children. The exact causes of attention deficit hyperactivity disorder are still not fully understood. Myelination deficiency in nerve fibers could be one of the possible factors in the pathogenesis of attention deficit hyperactivity disorder. Dopamine transporter knockout (DAT-KO) rats provide a good translational model for attention deficit hyperactivity disorder because they mimic behavioral symptoms of the disease: hyperactivity, cognitive impairment and compulsive behavior. This paper aims to determine abnormalities in the myelination process in the spinal cord of DAT-KO rats. Our findings can lead to a better understanding of the etiology and pathogenesis of attention deficit hyperactivity disorder.

AIM: To determine the mRNA expression levels of myelination-related genes in the spinal cord of dopamine transporter knockout (DAT-KO) rats during their natural development.

MATERIALS AND METHODS: The study was performed on 72 rat pups (DAT-KO, DAT-HET, DAT-WT) from 12 litters. Rat pups were born from the pairs of intercrossed DAT-HET x DAT-HET adult rats. Pups were decapitated on 7th, 14th and 21st day of their postnatal development. After that, mRNA levels of the main myelination-related genes were measured in the cervical and lumbar segments of the spinal cord using real-time PCR.

RESULTS: The mRNA levels of the mag, olig2 and plp1 genes were significantly different in the cervical and lumbar spinal cords of DAT-KO rats compared to DAT-WT animals. A significant increase in the level of mag gene mRNA in DAT-HET and DAT-KO animals was observed on 14th and 21st days of postnatal development. Also, in these animals, the olig2 mRNA levels were increased on the 21st day of postnatal development. The plp1 mRNA level was increased on the 14th day, and reduced on the 21st day of postnatal development in DAT-KO animals.

CONCLUSIONS: Myelination deficiency in nerve fibers in the spinal cord of DAT-KO rats is one of the effects of gene knockout. It is also of the possible causes of behavioral changes — hyperactivity, cognitive impairment and compulsive behavior.

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About the authors

Ekaterina D. Kulikova

Institute for Experimental Medicine

Email: kulikovaekaterina77@gmail.com
ORCID iD: 0009-0002-3218-1494

Laboratory Assistant, Pavlov Department of Physiology

Russian Federation, Saint Petersburg

Dmitry S. Traktirov

Institute for Experimental Medicine

Author for correspondence.
Email: ds.traktirov@gmail.com
ORCID iD: 0000-0003-0424-6545

Junior Researcher, Pavlov Department of Physiology

Russian Federation, Saint Petersburg

Marina N. Karpenko

Institute for Experimental Medicine

Email: mnkarpenko@mail.ru
ORCID iD: 0000-0002-1082-0059
SPIN-code: 6098-2715

Dr. Sci. (Biology), Head of Laboratory of Neurochemistry, Pavlov Department of Physiology

Russian Federation, Saint Petersburg

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2. Fig. 1. The mRNA levels of mag gene in cervical (a) and lumbar (b) spinal cord cells of DAT-HET and DAT-KO rat pups on 7th, 14th and 21st postnatal days. The values for DAT-WT rat pups were set as 1 (horizontal line). Data are presented as Mean ± SD (n = 8 for each group); * p < 0.05, ** p < 0.01 compared to DAT-WT group; 2-way ANOVA

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3. Fig. 2. The mRNA levels of olig2 gene in cervical (a) and lumbar (b) spinal cord cells of DAT-HET and DAT-KO rat pups on 7th, 14th and 21st postnatal days. The values for DAT-WT rat pups were set as 1 (horizontal line). Data are presented as Mean ± SD (n = 8 for each group); * p < 0.05, ** p < 0.01 compared to DAT-WT group; 2-way ANOVA

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4. Fig. 3. The mRNA levels of plp1 gene in cervical (a) and lumbar (b) spinal cord cells of DAT-HET and DAT-KO rat pups on 7th, 14th and 21st postnatal days. The values for DAT-WT rat pups were set as 1 (horizontal line). Data are presented as Mean ± SD (n = 8 for each group); * p < 0.05, ** p < 0.01 compared to DAT-WT group; 2-way ANOVA

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