Myelin genes expression in the spinal cord of dopamine transporter knockout rats



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Abstract

Background. Attention deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders affecting children. The exact causes of ADHD are still not fully understood. Myelination deficiency in nerve fibers could be one of the possible factors in the pathogenesis of ADHD. Dopamine transporter knockout (DAT-KO) rats provide a good translational model for ADHD 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 ADHD.

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

Materials and methods. The work 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 21st day of postnatal development. The plp1 mRNA level was increased on 14th day, and reduced on 21st day of postnatal development in DAT-KO animals.

Conclusions. Myelination deficiency in nerve fibers in 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.

About the authors

Ekaterina Denisovna Kulikova

FSBSI "Institute of experimental medicine"

Email: kulikovaekaterina77@gmail.com
ORCID iD: 0009-0002-3218-1494
Russian Federation, 12, Acad. Pavlov Street 197376, St. Petersburg

Dmitrii Traktirov

FSBSI "Institute of experimental medicine"

Author for correspondence.
Email: ds.traktirov@gmail.com
ORCID iD: 0000-0003-0424-6545
Russian Federation, 12, Acad. Pavlov Street 197376, St. Petersburg

Marina Karpenko

FSBSI "Institute of experimental medicine"

Email: mnkarpenko@mail.ru
ORCID iD: 0000-0002-1082-0059
Russian Federation, 12, Acad. Pavlov Street 197376, St. Petersburg

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