Neuromorphological Atlas of Human Prenatal Brain Development: White Paper.

Recent morphological data on human brain development are quite fragmentary. However, they are highly requested for a number of medical practices, educational programs, and fundamental research in the fields of embryology, cytology and histology, neurology, physiology, path anatomy, neonatology, and others. This paper provides the initial information on the new online Human Prenatal Brain Development Atlas (HBDA). The Atlas will start with forebrain annotated hemisphere maps, based on human fetal brain serial sections at the different stages of prenatal ontogenesis. Spatiotemporal changes in the regional-specific immunophenotype profiles will also be demonstrated on virtual serial sections. The HBDA can serve as a reference database for the neurological research, which provides opportunity to compare the data obtained by noninvasive techniques, such as neurosonography, X-ray computed tomography and magnetic resonance imaging, functional magnetic resonance imaging, 3D high-resolution phase-contrast computed tomography visualization techniques, as well as spatial transcriptomics data. It could also become a database for the qualitative and quantitative analysis of individual variability in the human brain. Systemized data on the mechanisms and pathways of prenatal human glio- and neurogenesis could also contribute to the search for new therapy methods for a large spectrum of neurological pathologies, including neurodegenerative and cancer diseases. The preliminary data are now accessible on the special HBDA website.

The coincidence of two rare diseases with opposite metabolic phenotype: a child with congenital hyperinsulinism and Bloom syndrome.

OBJECTIVES: Congenital hyperinsulinism (CHI) is a group of rare genetic disorders characterized by insulin overproduction. CHI causes life-threatening hypoglycemia in neonates and infants. Bloom syndrome is a rare autosomal recessive disorder caused by mutations in the BLM gene resulting in genetic instability and an elevated rate of spontaneous sister chromatid exchanges. It leads to insulin resistance, early-onset diabetes, dyslipidemia, growth delay, immune deficiency and cancer predisposition. Recent studies demonstrate that the BLM gene is highly expressed in pancreatic islet cells and its mutations can alter the expression of other genes which are associated with apoptosis control and cell proliferation. CASE PRESENTATION: A 5-month-old female patient from consanguineous parents presented with drug-resistant CHI and dysmorphic features. Genetic testing revealed a homozygous mutation in the KCNJ11 gene and an additional homozygous mutation in the BLM gene. While 18F-DOPA PET scan images were consistent with a focal CHI form and intraoperative frozen-section histopathology was consistent with diffuse CHI form, postoperative histopathological examination revealed features of an atypical form. CONCLUSIONS: In our case, the patient carries two distinct diseases with opposite metabolic phenotypes.

Structure of neuro-endocrine and neuro-epithelial interactions in human foetal pancreas.

In the pancreas of many mammals including humans, endocrine islet cells can be integrated with the nervous system components into neuro-insular complexes. The mechanism of the formation of such complexes is not clearly understood. The present study evaluated the interactions between the nervous system components, epithelial cells and endocrine cells in the human pancreas. Foetal pancreas, gestational age 19-23 weeks (13 cases) and 30-34 weeks (7 cases), were studied using double immunohistochemical labeling with neural markers (S100 protein and beta III tubulin), epithelial marker (cytokeratin 19 (CK19)) and antibodies to insulin and glucagon. We first analyse the structure of neuro-insular complexes using confocal microscopy and provide immunohistochemical evidences of the presence of endocrine cells within the ganglia or inside the nerve bundles. We showed that the nervous system components contact with the epithelial cells located in ducts or in clusters outside the ductal epithelium and form complexes with separate epithelial cells. We observed CK19-positive cells inside the ganglia and nerve bundles which were located separately or were integrated with the islets. Therefore, we conclude that neuro-insular complexes may forms as a result of integration between epithelial cells and nervous system components at the initial stages of islets formation.