Dopamine receptors and key elements of the neurotrophins (BDNF, CDNF) expression patterns during critical periods of ontogenesis in the brain structures of mice with autism-like behavior (BTBR) or its absence (С57BL/6 J).

Analysis of the mechanisms underlying autism spectrum disorder (ASD) is an urgent task due to the ever-increasing prevalence of this condition. The study of critical periods of neuroontogenesis is of interest, since the manifestation of ASD is often associated with prenatal disorders of the brain development. One of the currently promising hypotheses postulates a connection between the pathogenesis of ASD and the dysfunction of neurotransmitters and neurotrophins. In this study, we investigated the expression of key dopamine receptors (Drd1, Drd2), brain-derived neurotrophic factor (Bdnf), its receptors (Ntrkb2, Ngfr) and the transcription factor Creb1 that mediates BDNF action, as well as cerebral dopamine neurotrophic factor (Cdnf) during the critical periods of embryogenesis (e14 and e18) and postnatal development (p14, p28, p60) in the hippocampus and frontal cortex of BTBR mice with autism-like behavior compared to the neurotypical C57BL/6 J strain. In BTBR embryos, on the 14th day of prenatal development, an increase in the expression of the Ngfr gene encoding the p75NTR receptor, which may lead to the activation of apoptosis, was found in the hippocampus and frontal cortex. A decrease in the expression of Cdnf, Bdnf and its receptor Ntrkb2, as well as dopamine receptors (Drd1, Drd2) was detected in BTBR mice in the postnatal period of ontogenesis mainly in the frontal cortex, while in the hippocampus of mature mice (p60), only a decrease in the Drd2 mRNA level was revealed. The obtained results suggest that the decrease in the expression levels of CDNF, BDNF-TrkB and dopamine receptors in the frontal cortex in the postnatal period can lead to significant changes in both the morphology of neurons and dopamine neurotransmission in cortical brain structures. At the same time, the increase in p75NTR receptor gene expression observed on the 14th day of embryogenesis, crucial for hippocampus and frontal cortex development, may have direct relevance to the manifestation of early autism.

Effect of NO Synthesis Blockade on the Hydrouretic Function and Extracellular Matrix of the Kidneys in Rats with Different Blood Vasopressin Levels.

We studied the effect of NO synthesis blockade on the hydrouretic function and the state of renal interstitial matrix in WAG rats with normal blood vasopressin level and Brattleboro rats lacking endogenous vasopressin. In WAG rats, impaired osmotic concentration accompanied by an increase in the content of histochemically detectable glycosaminoglycans in the inner medullary interstitium was observed under conditions of NO synthesis blockade. In Brattleboro rats, NO synthesis inhibition, on the contrary, induced an antidiuretic response without significant changes in the renal extracellular matrix. These findings attested to a significant influence of NO on the urine concentration process. Morphofunctional changes in the kidneys under conditions of NO synthesis blockade are determined by blood vasopressin level.