TY - JOUR

T1 - Stable Dopamine-Signaling mRNA Co-Expression in the Substantia Nigra Is Deregulated in Pathological Conditions, but Not in Dopamine Transporter Knockout Rats

AU - Ваганова, Анастасия Николаевна

AU - Фесенко, Зоя Сергеевна

AU - Вольнова, Анна Борисовна

AU - Гайнетдинов, Рауль Радикович

PY - 2025/8/3

Y1 - 2025/8/3

N2 - Dopamine transporter (DAT) mutations are associated with neurological and psychiatric diseases, and DAT gene knockout in rats (DAT-KO) provides an opportunity to evaluate the DAT role in pathological conditions. We analyzed DAT expression and co-expression with other genes in the substantia nigra and striatum in public transcriptomic data represented in the GEO repository and then estimated the identified DAT co-expression pattern in DAT-KO rats by RT-PCR. In silico analysis confirmed DAT expression in the substantia nigra and absence of DAT mRNA in the striatum. Also, DAT is co-expressed with genes involved in dopamine signaling, but these associations are disrupted in dopamine neuron-damaging conditions. To estimate this co-expression pattern when DAT expression is lost, we evaluate it in the substantia nigra of DAT-KO rats. However, in DAT-KO rats the associations between genes involved in dopamine signaling were not disturbed compared to wild-type littermates, and tyrosine hydroxylase expression upregulation in the substantia nigra of these animals may be considered as compensation for the loss of dopamine reuptake. Further studies of expression regulation in dopamine neurons of DAT-KO rats may provide valuable information for compensatory mechanisms in substantia nigra dopaminergic neurons.

AB - Dopamine transporter (DAT) mutations are associated with neurological and psychiatric diseases, and DAT gene knockout in rats (DAT-KO) provides an opportunity to evaluate the DAT role in pathological conditions. We analyzed DAT expression and co-expression with other genes in the substantia nigra and striatum in public transcriptomic data represented in the GEO repository and then estimated the identified DAT co-expression pattern in DAT-KO rats by RT-PCR. In silico analysis confirmed DAT expression in the substantia nigra and absence of DAT mRNA in the striatum. Also, DAT is co-expressed with genes involved in dopamine signaling, but these associations are disrupted in dopamine neuron-damaging conditions. To estimate this co-expression pattern when DAT expression is lost, we evaluate it in the substantia nigra of DAT-KO rats. However, in DAT-KO rats the associations between genes involved in dopamine signaling were not disturbed compared to wild-type littermates, and tyrosine hydroxylase expression upregulation in the substantia nigra of these animals may be considered as compensation for the loss of dopamine reuptake. Further studies of expression regulation in dopamine neurons of DAT-KO rats may provide valuable information for compensatory mechanisms in substantia nigra dopaminergic neurons.

KW - Animals

KW - Corpus Striatum/metabolism

KW - Dopamine Plasma Membrane Transport Proteins/genetics

KW - Dopamine/metabolism

KW - Dopaminergic Neurons/metabolism

KW - Gene Expression Regulation

KW - Gene Knockout Techniques

KW - Male

KW - RNA, Messenger/genetics

KW - Rats

KW - Signal Transduction

KW - Substantia Nigra/metabolism

KW - Tyrosine 3-Monooxygenase/metabolism

UR - https://www.mendeley.com/catalogue/04eb0217-6911-3c39-9cf7-4dd55db3fd40/

U2 - 10.3390/biom15081117

DO - 10.3390/biom15081117

M3 - Article

C2 - 40867562

VL - 15

JO - Biomolecules

JF - Biomolecules

SN - 2218-273X

IS - 8

M1 - 1117

ER -