Primary and secondary olfactory centres in human ontogeny.

The olfactory centres are the evolutionary oldest and most conservative area of the telencephalon. Olfactory deficiencies are involved in a large spectrum of neurologic disorders and neurodegenerative diseases. The growing interest in human olfaction has been also been driven by COVID-19-induced transitional anosmia. Nevertheless, recent data on the human olfactory centres concerning normal histology and morphogenesis are rare. Published data in the field are mainly restricted to classic studies with non-uniform nomenclature and varied definitions of certain olfactory areas. While the olfactory system in model animals (rats, mice, and more rarely non-human primates) has been extensively investigated, the developmental timetable of olfactory centres in both human prenatal and postnatal ontogeny are poorly understood and unsystemised, which complicates the process of analysing human material, including medical researches. The main purpose of this review is to provide and discuss relevant morphological data on the normal ontogeny of the human olfactory centres, with a focus on the timetable of maturation and developmental cytoarchitecture, and with special reference to the definitions and terminology of certain olfactory areas.

[Differential diagnostic value of the expression of the transcription factor PDX-1 in neuroendocrine and non-neuroendocrine tumors of the pancreas and other organs]. / Differentsial'no-diagnosticheskoe znachenie ékspressii transkriptsionnogo faktora PDX-1 v neiroéndokrinnykh i neneiroéndokrinnykh opukholiakh podzheludochnoi zhelezy i drugikh organov.

An important role in the differentiation of tissues in different organs is played by transforming factors (TFs); pancreatic and duodenal homebox 1 (PDX-1) is one of the earliest factors for pancreatic cells. Many malignant tumors, including neuroendocrine tumors (NETs), are similar in structure, and therefore the actual problem of oncomorphology is to search for narrow-specific markers and TFs. AIM: to comparatively analyze and assess the value of the expression of the TF PDX-1 in NETs and non-NETs of different localization and histogenetic origin. MATERIAL AND METHODS: Anti-PDX-1 antibodies were used to study 528 tumors divided into 3 groups: Group 1 included 394 NETs, among them there were those of the pancreas (n=173), stomach (n=46), bowel (n=65), lung (n=40), thymus (n=8), kidney (n=6), Merkel's cell carcinomas (n=14), NETs of the breast (n=3), larynx (n=2), trachea (n=2), bladder (n=1), and metastatic NETs (n=34) of unknown primary site; Group 2 consisted of 16 tumors, of them there were paragangliomas (n=6), medullary thyroid cancers (MTC) (n=6) and adrenal pheochromocytomas (APCC) (n=4); Group 3 comprised 118 non-NETs, among them there were tumors of the pancreas (n=54), stomach (n=26), bowel (n=17), lung (n=11), breast (n=3), kidney (n=4), adrenal glands (n=2), and bladder (n=1). RESULTS: PDX-1 was positive in 75.1% (130/173) of pancreatic NETs, all insulinomas (50/50), gastrinomas (11/11), somatostatinomas (3/3), ACTH-producing tumors (2/2); PDX-1 was positive in the non-functioning pancreatic NETs, all PPomas (19/19), 76.1% (35/46) of NETs without the hormone detected, 50% (2/4) of calcitoninomas, and 21.1% (8/38) of silent glucagonomas. PDX-1 was positive in 32.4% (11/34) of carcinoids and 50% (6/12) of neuroendocrine carcinomas, all duodenal NETs (18/18), 90% (9/10) of rectal carcinoids and 30.8% (4/13) colonic carcinoids, 37.5% (3/8) of thymic/mediastinal carcinoids, 66.7% (4/6) of kidney carcinoids, and 37.5% (9/24) of metastatic NETs of unknown primary site. PDX-1 was negative in all carcinoids of the colon and sigmoid (0/5), ileum and jejunum (0/24), lung (0/40), trachea (0/2), larynx (0/2), Merkel's cell carcinoma (0/14), breast (0/3), bladder (0/1), as well as MTC (0/6), APCC (0/4), and paragangliomas (0/6). PDX-1-positive non-NETs included 81.8% (18/22) of adenocarcinomas (AC) and all serous cystic, mucinous cystic, intraductal and acinar cell tumors of the pancreas (4/4, 3/3, 2/2, and 3/3), 57.1% of AC (8/14) and 83.3% of signet ring cell carcinomas of the stomach (10/12), 56.2% AC of the bowel (9/17), bladder cancer (1/1). PDX-1 was negative in all anaplastic cancers (0/2) and solid pseudopapillary tumors of the pancreas (0/20), cancers of the lung (0/11), kidney (0/4), breast (0/3), and adrenal glands (0/2). CONCLUSION: The expression of PDX-1 is very specific for most digestive tract NETs and non-NETs. Pancreatic ductal and acinar cell tumors and gastric signet ring cell carcinomas are most commonly PDX-1-positive. Most tumors that do not originate from the digestive tract have a PDX-1 negative immunophenotype.

Pancreas of C57 black mice after long-term space flight (Bion-M1 Space Mission).

In this study, we analysed the pancreases of C57BL/6N mice in order to estimate the effects of long-term space flights. Mice were flown aboard the Bion-M1 biosatellite, or remained on ground in the control experiment that replicated environmental and housing conditions in the spacecraft. Vivarium control group was used to account for housing effects. Each of the groups included mice designated for recovery studies. Mice pancreases were dissected for histological and immunohistochemical examinations. Using a morphometry and statistical analysis, a strong correlation between the mean islet size and the mean body weight was revealed in all groups. Therefore, we propose that hypokinesia and an increase in nutrition play an important role in alterations of the endocrine pancreas, both in space flight and terrestrial conditions.

Immunohistochemical Analysis and Electron Microscopy of Glial Cells in the Pancreas of Fetuses and Children.

Schwann cells forming peri-insular glial sheath of the pancreatic islets in some mammals can be involved in the pathogenesis of diabetes mellitus. Human pancreatic cells contain small elongated or oval cells of unknown origin with S100-immunopositive processes. We found that cells with processes located in pancreatic islets of human fetuses and children are similar to Schwann cells by their morphological and ultrastructural characteristics, immunopositive reaction for S100, and integration with nerve endings. In the pancreas of fetuses and children, Schwann cells are often seen in forming pancreatic islets and around the pancreatic ducts. The data suggests that Schwann cells can participate in the morphogenesis of human pancreatic islets.

Distribution of chromogranin A in human fetal pancreas.

Immunohistochemical study of distribution of chromogranin A (neuroendocrine cell marker) in the developing human pancreas was carried out. Immunopositive reaction to chromogranin A was detected in the primordial pancreas from the early period of development (8 weeks). The count of chromogranin A-positive cells in early fetuses significantly surpassed that of insulin- and glucagon-containing cells. Chromogranin A immunoreactive cells, but not cells reacting with antibodies to insulin and glucagon were detected in the pancreatic islets and pancreatic ducts during all periods of gestation. These results suggested that hormone synthesis by pancreatic endocrine cells was preceded by the expression of chromogranin A and hence, this marker could be used for studies of the mechanisms of development of the endocrine part of the pancreas.

Immunohistochemical study of α- and ß-cell distribution in human pancreatic Langerhans islets of various types.

Various types of insulin- and glucagon-containing endocrine cell distribution were found by double staining with antibodies to insulin and glucagon in the pancreatic autopsy material from subjects without carbohydrate metabolism disorders. The cell composition of the islets and their morphogenetic maturity depended on the vascularization degree. Insulin-containing cells predominated in small clusters of endocrine cells and in islets with few capillaries, while glucagon predominated in large islets with rich vascularization. A scheme of development and differentiation of Langerhans islets in the adult human pancreas was presented.

Immunoreactivity of neuron-specific enolase (NSE) in human pancreas in health and type 1 diabetes mellitus.

The role of neuron-specific enolase (glycolytic enzyme; marker of nerve fibers and Langerhans islet in human pancreas) in the development of type 1 diabetes mellitus was studied in autopsy specimens from 6 adult patients. Autopsied specimens of the pancreas from 7 subjects without carbohydrate metabolism disorders served as the control. Autopsied specimens of the pancreas from a child with the clinical diagnosis of type 1 diabetes mellitus, a child without carbohydrate metabolism disorders, and from 7 human fetuses of 15-40 weeks gestation were also studied. In control specimens, the neuron-specific enolase was detected in the pancreatic nerve fibers and Langerhans islets. Studies of pancreatic tissue specimens from adult patients with type 1 diabetes mellitus showed no immunopositive reaction to neuron-specific enolase in insulin-negative specimens. A possible mechanism of type 1 diabetes mellitus development is suggested.

[Neurogenic mechanisms of development of type 1 diabetes mellitus].

Immunohistochemical (tests for insulin, glucagons, periferin, SNAP-25, GFAP, NGF-R, RMR-22, MBP) and morphological studies were performed to examine the pancreatic nervous apparatus of human adults and fetuses in late phases of development. A role of the morphogenetic activity of the pancreatic nervous apparatus was investigated in type 1 diabetes mellitus (DM-1). The neurons and gliocytes located in the pancreas are suggested to have a morphogenetic activity and form a glial capsule throughout their life. The insular endocrine cells are shown to synthesize the proteins (SNAP-25, GFAP) characteristic of nerve cells and their synaptic terminals. A neurobiological model of DM-1 'development has been stated. The onset of the disease is characterized by the development of autoimmune processes directed to the nervous system. In nerve tissue protein autoimmunization, the fine insular neuroglial membrane is rapidly disrupted. This leads to the transfer of autoimmune aggression to the insulin-producing cells of the islets of Langerhans, which carry specific nerve tissue proteins onto their surface. Recovery of the islets becomes impossible without forming a protective neuroglial membrane, which makes the development of DM-1 irreversible.

Morphogenesis of asymmetry of rat brain nuclei under normal conditions and during exposure to microgravitation.

Histological and morphometrical analysis of the brain and peripheral analyzers revealed proliferative migration abnormalities of brain development and neuron differentiation in mammals during a space flight, which can limit space exploration.

Asymmetry of human brain in early embryogenesis under normal and pathological conditions.

The effect of some developmental abnormalities on the morphogenesis of human brain asymmetry during early embryonic stages was studied. Insignificant predominance of the left hemisphere (1-3%) was revealed in human embryos.

[Study of amphibian brain asymmetry during normal embryonic and larval development]. / Issledovanie asimmetrii golovnogo mozga amfibii v normal'nom émbrional'nom i lichinochnom razvitii.

Amphibian embryos (Triturus vulgaris, Pleurodeles waltl, Hynobius keyserlingii, Ambystoma mexicanum, Rana temporaria, Bufo bufo, and Xenopus laevis) were investigated. We ascertained the morphological right-side asymmetry of the brain, which appears at the neurula stage and is preserved during the postembryonic (larval) development. In T. vulgaris, P. waltl, H. keyserlingii, and X. laevis, we observed right-side asymmetry of peripheral analyzers, such as the retina, ganglia of nerve VIII, and olfactory placodes. Structural analysis of the forebrain in A. mexicanum has shown that in the larvae, the pallium prevails on the left side of the cerebral hemisphere. During metamorphosis, left-side asymmetry is replaced by right-side, which is then preserved. We propose that the brain asymmetry arose at the early stages of evolution as a result of embryonic formation of the nervous system.