The Study of the State of Monoaminergic Systems in the Brain Structures of the Offsprings of Female BALB/C Mice at Different Stages of Formation of Autism Spectrum Disorders

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Abstract

The study of the status of norepinephrine-, dopamine- and serotonergic neurotransmitter systems of BALB/C mice brain structures on 15 and 64 days of postnatal development (PD) in the model of autistic disturbances induced by injection of of sodium valproate (SV, 400 mg/kg, s/c) to pregnant females was carried out using the HPLC/ED method. The level of both catechol- and indolamines in the brain structures of control group mice at the age of 15 days was significantly lower than in adult animals at the age of 64 days. Prenatal administration of SV caused a decrease in all parameters of monoaminergic neurotransmission in the striatum of offspring at the age of 15 days, but had no effect in other brain structures studied. Subsequently, the level of dopamine increased and by the 64th day of PD did not differ from the parameters of the control group. The parameters of the serotonergic system changed in a similar pattern, with the content of serotonin and the serotonin metabolite 5-OIAA in the striatum increasing gradually and reaching maximum values by the 64th day of PR. Our data allows to assume that the administration of SV to pregnant females affects the activity of the dopamine and serotonergic systems of the brain of the offspring, causing a decrease in their activity in the striatum by the 15th day of pregnancy, followed by restoration to control values by the 64th day, which we previously observed in male pups. Thus, the patterns of dynamic changes in the neurochemical profile do not differ between males and females.

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V. S. Kudrin

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Email: narvik@yandex.ru
Russian Federation, Moscow

V. B. Narkevich

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Author for correspondence.
Email: narvik@yandex.ru
Russian Federation, Moscow

A. A. Alymov

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Email: narvik@yandex.ru
Russian Federation, Moscow

I. G. Kapitsa

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Email: narvik@yandex.ru
Russian Federation, Moscow

K. A. Kasabov

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Email: narvik@yandex.ru
Russian Federation, Moscow

P. L. Naplekova

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Email: narvik@yandex.ru
Russian Federation, Moscow

N. V. Kudryashov

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Email: narvik@yandex.ru
Russian Federation, Moscow

T. A. Voronina

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Email: narvik@yandex.ru
Russian Federation, Moscow

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2. Fig. 1. Dynamics of changes in monoamine metabolism in the hypothalamus and striatum of female BALB/C mice whose mothers were injected with sodium valproate (400 mg/kg, n/a). White color is control, black color is sodium valproate. The numbers indicate the age of the animals: 1 — 15 days, 2 — 42 days, 3 — 64 days; * — p < 0.05; ** — p < 0.05; *** — p < 0.05. The data are presented as M ± SEM, statistical analysis was performed using two-factor analysis of variance (factors: 1) age and 2) effect of substances) followed by a post-hoc test according to the Newman—Kales criterion. Age: 1 — 15 days, 2 — 45 days, 3 — 65 days; * — p < 0.05; ** — p < 0.01 compared with the same substance in 15-day-old rats; # — p < 0.05; ## — p < 0.01 compared with the control of the same age; ＄ — p < 0.05; ＄＄ — p < 0.01 compared with the same substance in 45-day-old rats.

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3. Fig. 2. Dynamics of changes in monoamine metabolism in the frontal cortex and hippocampus of female BALB/C mice whose mothers were injected with sodium valproate (400 mg/kg, n/a). White color is control, black color is sodium valproate. The numbers indicate the age of the animals: 1 — 15 days, 2 — 42 days, 3 — 64 days; * — p < 0.05; ** — p < 0.05; *** — p < 0.05. The data are presented as M ± SEM, statistical analysis was performed using two-factor analysis of variance (factors: 1) age and 2) effect of substances) followed by a post-hoc test according to the Newman—Kales criterion. Age: 1 — 15 days, 2 — 45 days, 3 — 65 days; * — p < 0.05; ** — p < 0.01 compared with the same substance in 15-day-old rats; # — p < 0.05; ## — p < 0.01 compared with the control of the same age; ＄ — p < 0.05; ＄＄ — p < 0.01 compared with the same substance in 45-day-old rats.

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