A brief history of Russian research on the autonomic nervous system.

The first information on the structure and function of the autonomic nervous system dates back to the time of Galen (second century), while the beginning of the study of the autonomic nervous system in Russia can be traced back to the mid-19th century. This review is devoted to the professional achievements of Russian researchers in the 19th and 20th centuries who were active in the field of the autonomic nervous system at different stages of the development of neuromorphology and neurophysiology. In addition, recent achievements of modern Russian researchers active in this domain are also highlighted. This review is mainly devoted to research on the autonomic nervous system in Russia, but it would be unfair not to mention the scientists who made a significant contribution to this field of science and worked in the republics of the former USSR. Russian morphology and physiology developed under the significant influence of well-known western scientific schools. I sincerely hope that cooperation between Russian and foreign colleagues will continue and will be fruitful for global science.

Expression of calbindin and calretinin in the dorsomedial and ventromedial hypothalamic nuclei during aging.

The hypothalamus is involved in the regulation of rhythms, autonomic, endocrine, and behavioral functions and may also participate in aging development and control. The aim of this work was to study the expression of calbindin (CB) and calretinin (CR) in the ventromedial (VMH) and dorsomedial (DMH) hypothalamic nuclei in young and old rats of both sexes by immunohistochemistry and western blotting. In young animals, the largest number of CB-immunoreactive (IR) neurons was detected in the ventral part of DMH (DMHv) and smaller percentage was found in its dorsal part (DMHd), in the dorsomedial part of the VMH (VMHdm) and in the ventrolateral part of the VMH (VMHvl). In aged animals, the percentage of CB-IR neurons significantly decreased in all studied nuclei, including DMHv, DMHd, VMHdm and VMHvl. CR-IR neurons were found in moderate number in the DMHv, DMHd, VMHdm and VMHvl of young rats. In aged rats, the percentage of CR-IR neurons significantly increased in the DMHv, DMHd, VMHdm and VMHvl. Less than one third of IR neurons colocalized CB and CR in young and aged rats. The expression of CB significantly decreased, and the expression of CR significantly increased in the DMH and VMH during aging by western blot analysis. Thus, there are opposite changes of the calcium-binding proteins expression in the hypothalamic nuclei involved in the metabolic and sexual regulation during aging.

Development of Calbindin- and Calretinin-Immunopositive Neurons in the Enteric Ganglia of Rats.

Calbindin D28 K (CB) and calretinin (CR) are the members of the EF-hand family of calcium-binding proteins that are expressed in neurons and nerve fibers of the enteric nervous system. CB and CR are expressed differentially in neuronal subpopulations throughout the central and peripheral nervous systems and their expression has been used to selectively target specific cell types and isolate neuronal networks. The present study presents an immunohistochemical analysis of CB and CR in the enteric ganglia of small intestine in rats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old, 60-day-old, 1-year-old, and 2-year-old). The data obtained suggest a number of age-dependent changes in CB and CR expression in the myenteric and submucous plexuses. In the myenteric plexus, the lowest percentage of CB-immunoreactive (IR) and CR-IR neurons was observed at birth, after which the number of IR cells increased in the first 10 days of life. In the submucous plexus, CB-IR and CR-IR neurons were observed from 10-day-old onwards. The percentage of CR-IR and CB-IR neurons increased in the first 2 months and in the first 20 days, respectively. In all animals, the majority of the IR neurons colocalized CR and CB. From the moment of birth, the mean of the cross-sectional area of the CB-IR and CR-IR neuronal profiles was larger than that of CB- and CR-negative cells.

Development of neuropeptide Y-mediated heart innervation in rats.

Neuropeptide Y (NPY) plays a trophic role in the nervous and vascular systems and in cardiac hypertrophy. However, there is no report concerning the expression of NPY and its receptors in the heart during postnatal development. In the current study, immunohistochemistry and Western blot analysis was used to label NPY, and Y1R, Y2R, and Y5R receptors in the heart tissue and intramural cardiac ganglia from rats of different ages (newborn, 10 days old, 20 days old, 30 days old, 60 days old, 1 year old, and 2 years old).The obtained data suggest age-dependent changes of NPY-mediated heart innervation. The density of NPY-immunoreactive (IR) fibers was the least in newborn animals and increased in the first 20 days of life. In the atria of newborn and 10-day-old rats, NPY-IR fibers were more abundant compared with the ventricles. The vast majority of NPY-IR fibers also contained tyrosine hydroxylase, a key enzyme in catecholamine synthesis.The expression of Y1R increased between 10 and 20 days of life. Faint Y2R immunoreactivity was observed in the atria and ventricles of 20-day-old and older rats. In contrast, the highest level of the expression of Y5R was found in newborn pups comparing with more adult rats. All intramural ganglionic neurons were also Y1R-IR and Y5R-IR and Y2R-negative in all studied animals.Thus, the increasing of density of NPY-containing nerve fibers accompanies changes in relation of different subtypes of NPY receptors in the heart during development.

Development of non-catecholaminergic sympathetic neurons in para- and prevertebral ganglia of cats.

Expression of vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT) and calcitonin gene-related peptide (CGRP) in the sympathetic ganglia was investigated by immunohistochemistry in the superior cervical ganglion (SCG), stellate ganglion (SG) and celiac ganglion (CG) from cats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old and 2-month-old). Non-catecholaminergic TH-negative VIP-immunoreactive (IR) and nNOS-IR sympathetic ganglionic neurons are present from the moment of birth. In all studied age groups, substantial populations of VIP-IR (up to 9.8%) and nNOS-IR cells (up to 8.3%) was found in the SG, with a much smaller population found in the SCG (<1%) and only few cells observed in the CG. The percentage of nNOS-IR and VIP-IR neurons in the CG and SCG did not significantly change during development. The proportion of nNOS-IR and VIP-IR neuron profiles in the SG increased in first 20 days of life from 2.3±0.15% to 8.3±0.56% and from 0.3±0.05% to 9.2±0.83%, respectively. In the SG, percentages of nNOS-IR sympathetic neurons colocalizing VIP increased in the first 20 days of life. ChAT-IR and CGRP-IR neurons were not observed in the sympathetic ganglia of newborn animals and did not appear until 10 days after birth. In the SG of newborn and 10-day-old kittens, the majority of NOS-IR neurons were calbindin (CB)-IR, whereas in the SCG and CG of cats of all age groups and in the SG of 30-day-old and older kittens, the vast majority of NOS-IR neurons lacked CB. We conclude that the development of various non-catecholaminergic neurons in different sympathetic ganglia has its own time dynamics and is concluded at the end of the second month of life.

Development of neuropeptide Y-containing neurons in sympathetic ganglia of rats.

Expression of neuropeptide Y (NPY) in the sympathetic ganglia was investigated by immunohistochemistry and tract tracing. The distribution of NPY immunoreactivity (IR) was studied in the superior cervical ganglion (SCG), stellate ganglion (SG) and celiac ganglion (CG) from rats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old, 2-month-old, 6-month-old, 24-month-old). We observed that the percentage of NPY-IR neuronal profiles increased during early postnatal development. In the SCG and SG, the percentage of NPY-IR profiles enlarged in the first month of life from 43±3.6% (SCG) and 46±3.8% (SG) until 64±4.1% (SCG) and 58±3.5% (SG). The percentage of NPY-IR profiles in the CG increased during the period between 20days (65±3.8%) and 30days (82±5.1%) of animals' life and did not change in further development. In newborn and 10-day-old rats, a large portion of NPY-IR neurons was also calbindin D28K (CB)-IR in all sympathetic ganglia. The proportion of CB-IR substantially decreased during next 10days in the SCG, SG and CG. NPY-IR was approximately present in a half of the postganglionic neurons innervating muscle vessels of the neck and forearm, and the percentage of labeled NPY-IR profiles did not change during the development. Only single Ki67-IR neurons were also NPY-IR in the SCG, SG and CG in newborns and not in older animals. No NPY+/caspase 3+IR neurons were observed. Finally, the process of morphological changes in the size and percentages of NPY-IR profiles is complete in rats by the first month of life.

Calbindin-D28k immunoreactivity in sympathetic ganglionic neurons during development.

Expression of CB in the sympathetic ganglia was investigated by immunohistochemistry. The distribution of CB immunoreactivity was studied in the superior cervical ganglion (SCG), stellate ganglion (SG) and celiac ganglion (CG) from rats and cats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old, two-month-old, six-month-old). We observed that the percentage of CB-immunoreactive (IR) neurons decreased during early postnatal development in rats and cats. In all studied ganglia of both species, the percentage of CB-IR neurons was high in newborn and 10-day-old animals and significantly decreased up to 30 days of life. In rats of all ages, the largest percentage of CB-IR neurons was observed in the SG compared to the SCG and CG. In the cat sympathetic ganglia, the number of CB-IR neurons decreased more rapidly during the first two months of life, and only scattered CB-IR neurons were found in the sympathetic ganglia of two-month-old and six-month-old cats. In cats, the highest percentage of CB-IR neurons was observed in the SG, while the lowest percentage was found in the CG. The difference in size between CB+ and CB- neurons equally changed during development. Finally, the changes in the size and percentages of CB-IR neurons were complete in rats at the first month of life, and in cats at the end of the second month.

Development of the NADPH-diaphorase-positive neurons in the sympathetic ganglia.

Changes in the distribution of NADPH-diaphorase (NADPH-d) were studied in neurons of the superior cervical ganglion (SCG), stellate ganglion (SG) and celiac ganglia (CG) in newborn, 10-, 20-day-old, 1-month-old, 2-month-old and 6-month-old rats, mice and kittens. NADPH-d-positive neurons were revealed in all sympathetic ganglia in kittens but not in rodents from birth onwards. In kittens, the largest population of NADPH-d-positive cells was found in the SG, the smallest in the SCG (<1%) and we observed only a few cells in the CG. The proportion of NADPH-d-positive cells in the SG increased from 3.1 +/- 0.15% in newborn kittens to 9.3 +/- 0.63% in 20-day-old animals and decreased further from 8.1 +/- 0.75% in 30-day-old kittens to 3.4 +/- 0.54% in 2-month-old animals. The content of NADPH-d-positive cells in the CG and SCG did not change during development. There were no differences in cross-sectional area between neurons located in different ganglia of animals from the same age group under study. We conclude that the development of NADPH-d-positive neurons in different sympathetic ganglia has its own time dynamics and is completed by the end of the second month of life.

Afferent innervation of the trachea during postnatal development.

Retrograde axonal transport of horseradish peroxidase was used in this study to determine the location and basic morphological parameters of neurons innervating the trachea in newborn, 10-, 20-, 30-day-old and 2-month-old kittens. Labeled neurons were detected in all animals in the nodose ganglion of the vagus nerve and in the spinal ganglia (C1-C7 and T1-T6 after injection of tracer into the cervical trachea, C5-C7 and T1-T8 with injection into the thoracic part of the trachea) from both sides. The content of vagal and spinal afferent neurons innervating the cervical part of trachea declined during development. The number of spinal afferent neurons with connections to the thoracic trachea did not change but the quantity of cells in nodose ganglion supplying the thoracic trachea increased from the moment of birth till 10 and 20 days and decreased later in postnatal development. In newborn, 10-day-old and 20-day-old animals, the largest number of afferent cells was connected with the cervical part of the trachea in comparison with the thoracic one, whereas in 2-month-old kittens the relation was opposite. We suggest that afferent innervation of the trachea is not morphologically complete at the moment of birth and does not become mature until the second month of life.

Histochemical features of neurons in the cat stellate ganglion during postnatal ontogenesis.

Changes in the distribution of NADPH-diaphorase (NADPH-d) and acetylcholinesterase (AChE) were studied in neurons of the stellate ganglion in newborn, 10-, 20-day-old, 1-, 2-, 4- and 6-month-old kittens. AChE-positive neurons were revealed in the stellate ganglion (SG) from birth onwards. The number of these neurons increased until 20 days of postnatal life and then declined in 1- and 2-month-old kittens. A small number of weakly stained, NADPH-d-positive cells were found in newborn kittens, while intensely stained neurons first appeared in 10-day-old animals and increased in number up to the second month of life. The size of AChE-positive neurons was larger in comparison with NADPH-d-positive cells in the stellate ganglion of all animals under study. We suggest that putative vasodilator neurons or cells innervating sweat glands exhibit different development patterns from the moment of birth.