Volume 54, Nº 1 (2023)

Serotonin is not only a neurotransmitter, but also an important humoral regulator of various physiological processes outside the central nervous system. In the last decade, the concept of local serotonergic systems in peripheral organs, where serotonin realizes its effects via autocrine/paracrine mechanisms, has been developing. Such local systems have already been described in the pancreas, thymus, mammary gland, and bone marrow. We consider that a similar local serotonergic system is also characteristic of the adrenal glands. These paired organs are a key component of the mammalian endocrine system, providing a complex physiological response to stress. The adrenal glands consist of two parts distinct in origin and function – the cortex and medulla, while serotonin plays an important role in regulation of hormone secretion in both of these structures. This review is aimed to analyze the structure of the local serotonergic system in the adrenal gland, as well as its role both in the regulation of adrenal functions in adult animals and in the formation of adrenals in embryogenesis. Analysis of the available data suggests that local serotonergic systems makes an organ susceptible to fluctuations in the level of serotonin circulating in the blood at all stages of ontogenesis. Thus, local sensitivity to serotonin provides the possibility of systemic humoral coordination of the development and functioning of the adrenal glands and other peripheral organs. From this perspective, the importance of local serotoninergic systems for developmental biology and medicine gains insight.

It is believed that the nucleolus organizer region (NOR) in the ovary of adult birds is inactivated at all stages of oocyte growth. However, in the ovary of juvenile chicken (Gallus g. domesticus) one or two nucleoli were observed in 50% of early diplotene oocytes. These nucleoli were functioning up to the lampbrush stage. It was assumed that diplotene oocytes with inactivated NOR are stored as a pool for development in the ovary of adult hens. Such a contradiction in the NOR functional activity in the oocytes of juvenile and adult hens required special studies. Here we represent new results of a comparative study of the nucleoli in oocytes of juvenile and adult hens. We show for the first time that in the oocytes of laying hens the nucleolus appears at the early diplotene stage and the pre-rRNA synthesis continues up to the lampbrush stage. At the lampbrush stage, the NOR is getting inactivated. The nucleolus disintegrates into large fragments containing both pre-rRNA and fibrillarin. Then these larger fragments break down into small granules that do not contain pre-rRNA but contain fibrillarin. The results resolve the above contradiction and demonstrate a similar pattern of NOR functioning in oocytes of adult and juvenile birds.

One of the most important events in the embryonic development of mammals is the division of the ectoderm into integumentary and neuroectoderm. Signaling cascades induced by growth factors and cytokines involved in these processes have been studied in detail in recent decades. At the same time, the contribution of extracellular matrix (ECM) to these differentiation lineages remains unknown for mammals, while the significance of ECM in this process has been shown in other model organisms. To assess the effect of ECM on the formation of ectodermal derivatives, we modeled the neural and epidermal differentiation of human induced pluripotent stem cells (iPSCs) using substrates consisting of various ECM molecules; and also studied the involvement of one of the central links of the ECM signaling cascades, a transcriptional coactivator YAP1 in differentiation processes. Our results revealed the stimulatory effect of laminin 332 on the early stages of epidermal differentiation and of type I and III collagens on the inducing of the glial fate of late neural differentiation.

The pathological variant p.G2019S in the LRRK2 gene leads to the occurrence of a hereditary form of Parkinson’s disease (PD) and affects 7% of patients with a familial form of the disease. However, the mechanisms that trigger pathological events during the development of the disease are not yet fully understood. We obtained iPSCs (ICGi043-A line) from peripheral blood mononuclear cells of a patient with a hereditary form of PD associated with the genetic variant c.6055G>A (p.G2019S, rs34637584) in the LRRK2 gene using transfection with episomal vectors. iPSCs rapidly proliferate in dense monolayer cell colonies, are positive for endogenous alkaline phosphatase, have a normal karyotype (46,XX), express pluripotency markers (OCT4, SOX2, NANOG, TRA-1-60, SSEA-4) and are able to differentiate into three germ layers (ecto-, endo- and mesoderm), which confirms their pluripotent status. Future directed differentiation of the obtained iPSCs into dopaminergic neurons will allow the creation of an in vitro cell model of PD associated with the pathological variant c.6055G>A in the LRRK2 gene, and contribute to understanding the pathogenesis of PD.

Parkinson’s disease is a neurodegenerative disorder with a range of causes, only 5% of which can be explained by known genetic variants. We revealed polymorphisms in LRRK2 and PINK1 genes of a person with parkinsonism cases in family anamnesis. PBMCs of the patient were reprogrammed with a non-integrating episomal vectors to generate an induced pluripotent stem cell (iPSC) line. The iPSC line showed typical morphology and normal karyotype, expressed pluripotency markers, and was capable to differentiate into three germ layers. The iPSCs represent a valuable tool for investigating a potential implication of the genetic variants into the Parkinson’s disease pathogenesis.

Parkinson’s disease is a multifactorial disease; both genetic predisposition (5% of all cases), environmental factors and age-related changes in the brain and other body systems contribute to its etiology. For the diagnosis and study of the pathology of the development of the disease, it is important to search for new polymorphisms associated with hereditary forms of the disease. We analyzed the clinical exome of a 55-year-old patient with Parkinson’s disease and identified a single nucleotide polymorphism in the GLUD2 gene (c.1492T>G). This genetic variant is pathogenic according to the ClinVar database, but the mechanism of pathogenesis is still poorly understood. In addition, there are currently no relevant models based on human cells, which is of great interest. We generated induced pluripotent stem cells (iPSCs) from patient peripheral blood mononuclear cells using non-integrating episomal vectors expressing OCT4, KLF4, L‑MYC, SOX2, LIN28, and p53 shRNA. The obtained iPSC lines (ICGi044-B and ICGi044-C) demonstrate typical ESC-like morphology, normal karyotype (46,XY), express pluripotency markers (OCT4, SOX2, NANOG, SSEA4, TRA-1-60) and are able to give derivatives of three germ layers. The iPSC lines ICGi044-B and ICGi044-C, as well as their neural derivatives, represent an unique in vitro cell model for studying the pathogenetic mechanisms of the development of Parkinson’s disease associated with the c.1492T>G mutation in the GLUD2 gene.