TY - JOUR

T1 - Antioxidant system alterations and physiological characteristics of neonatal and juvenile DAT-KO rats

AU - Апрятин, Сергей Алексеевич

AU - Трактиров, Д. С.

AU - Карпенко, Марина Николаевна

AU - Ивлева, Ирина Сергеевна

AU - Пестерева, Нина Сергеевна

AU - Большакова, М. В.

AU - Трофимов, Александр Николаевич

AU - Фесенко, Зоя Сергеевна

AU - Клименко, Виктор Матвеевич

PY - 2023/10

Y1 - 2023/10

N2 - Dopamine transporter knockout (DAT-KO) rats represent a valuable rodent model for studying the molecular and phenotypical outcomes of the effects of excessive dopamine accumulation in the synaptic cleft and the prolonged action of dopamine on neurons. Animals with DAT deficiency are characterized by hyperactivity, stereotypy, cognitive deficits, and impairments in behavioral and biochemical indicators. Several key pathophysiological mechanisms are known to be common to psychiatric, neurodegenerative, metabolic, and other diseases. Among these mechanisms, oxidative stress systems play a particularly important role. One of the main antioxidant systems in the brain is glutathione: specifically, glutathione S-transferase, glutathione reductase, and catalase play a significant role in the regulation of vital oxidative processes, and their dysfunction has been shown in Parkinson's disease, Alzheimer's disease, and other neurodegenerative diseases. The current study aimed to analyze the dynamics of the activity levels of glutathione reductase and glutathione S-transferase in erythrocytes, as well as catalase in the blood plasma, of DAT-deficient, homo- and heterozygous, neonatal and juvenile rats (both male and female). Their behavioral and physiological parameters were evaluated at the age of 1.5 months. For the first time, changes in physiological and biochemical parameters were shown in DAT-KO rats at 1.5 months of postnatal life. The key role of glutathione S-transferase, glutathione reductase, and catalase in the regulation of oxidative stress in DAT-KO rats at the 5th week of life was demonstrated. A positive effect of a slightly increased dopamine level on memory function was shown in DAT-heterozygous animals.

AB - Dopamine transporter knockout (DAT-KO) rats represent a valuable rodent model for studying the molecular and phenotypical outcomes of the effects of excessive dopamine accumulation in the synaptic cleft and the prolonged action of dopamine on neurons. Animals with DAT deficiency are characterized by hyperactivity, stereotypy, cognitive deficits, and impairments in behavioral and biochemical indicators. Several key pathophysiological mechanisms are known to be common to psychiatric, neurodegenerative, metabolic, and other diseases. Among these mechanisms, oxidative stress systems play a particularly important role. One of the main antioxidant systems in the brain is glutathione: specifically, glutathione S-transferase, glutathione reductase, and catalase play a significant role in the regulation of vital oxidative processes, and their dysfunction has been shown in Parkinson's disease, Alzheimer's disease, and other neurodegenerative diseases. The current study aimed to analyze the dynamics of the activity levels of glutathione reductase and glutathione S-transferase in erythrocytes, as well as catalase in the blood plasma, of DAT-deficient, homo- and heterozygous, neonatal and juvenile rats (both male and female). Their behavioral and physiological parameters were evaluated at the age of 1.5 months. For the first time, changes in physiological and biochemical parameters were shown in DAT-KO rats at 1.5 months of postnatal life. The key role of glutathione S-transferase, glutathione reductase, and catalase in the regulation of oxidative stress in DAT-KO rats at the 5th week of life was demonstrated. A positive effect of a slightly increased dopamine level on memory function was shown in DAT-heterozygous animals.

KW - catalase

KW - dopamine transporter

KW - glutathione S-transferase

KW - glutathione reductase

KW - oxidative stress

UR - https://www.mendeley.com/catalogue/6eb08f07-605b-3573-8b01-7ded3041b58f/

U2 - 10.1002/jnr.25228

DO - 10.1002/jnr.25228

M3 - Article

VL - 101

SP - 1651

EP - 1661

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 10

ER -