Oxygen-sensing cells release neurotransmitters, including serotonin, in response to hypoxia in the blood or surrounding air/water. This stimulates the glossopharyngeal and/or vagal nerves, triggering increased ventilation via the respiratory reflex. In the adult, they are located in the carotid body (glomus cells) and lung epithelia (pulmonary neuroendocrine cells) of amniotes, and in the epithelia of the gills and orobranchial cavity (‘neuroepithelial cells’) of anamniotes. Despite their physiological importance, little is known about the molecular mechanisms of their development, while the evolutionary relationships between the various oxygen-sensing cell types are unknown. The chromaffin cells of the mammalian adrenal medulla are hypoxia-sensitive transiently during neonatal life. Both carotid body glomus cells and adrenal chromaffin cells arise from the neural crest and require the transcription factors Phox2b and Ascl1 for their development. Given these similarities, I aimed to test the hypothesis that the same molecular mechanisms underlie their development. Expression analysis of 13 sympathoadrenal pathway genes throughout chicken carotid body development revealed striking similarities with adrenal chromaffin cell development. Analysis of mouse mutants showed that the transcription factors Hand2, Sox4 and Sox11 are required for carotid body development. In addition, loss of the receptor tyrosine kinase Ret or the transcription factor AP-2β, which significantly affects sympathetic ganglion but not adrenal chromaffin cell development, has no effect on the carotid body. Adrenal chromaffin cells differentiate from neurons that migrate into the adrenal gland from ‘primary’ sympathetic ganglia at the dorsal aorta. Carotid body glomus cells were previously proposed to arise from neuronal “émigrés” from neighbouring ganglia: the superior cervical ganglion in mammals and the nodose ganglion in the chick. However, nodose neurons are considered to be nodose placode-derived. Using electroporation and grafting in the chick, I confirmed that the nodose placode does not contribute to the carotid body, identified a small population of autonomic neural crest-derived neurons in the nodose ganglion, and confirmed the existence of “bridges” of neurons between the nodose ganglion and the carotid body. My data suggest that, like adrenal chromaffin cells, carotid body glomus cells differentiate from autonomic neural crest-derived neurons in nearby ganglia, which migrate into the carotid body primordium and down-regulate neuronal markers. The proposed evolutionary relationship between the carotid body glomus cells and the serotonin-positive neuroepithelial cells of anamniote gills has never been tested. Using vital dye labelling, neural fold grafts, genetic lineage-tracing in zebrafish and analysis of zebrafish mutants lacking all neural crest cells, I found that serotonin-positive cells in the gills and orobranchial epithelia of lamprey (jawless fish), zebrafish (ray-finned bony fish) and frog (anamniote tetrapod) are not neural crest-derived, and hence are not homologous to carotid body glomus cells. Genetic lineage-tracing in mouse and neural fold grafts in chick also confirmed that serotonin-positive neuroendocrine cells in the lung are not neural crest- derived, hence must have an endodermal origin (since the lungs are out-pocketings of the gut). My results suggest that the neuroepithelial cells of anamniotes are not related to carotid body glomus cells, but rather are homologous to the oxygen-sensing cells of the lung. Consistent with this hypothesis, I found that many genes expressed during carotid body development are not expressed by the epithelia of either chick lungs or lamprey gills. Taken together, my data suggest that as air-breathing evolved, gut endoderm- derived cells that originally responded to hypoxia in water were maintained in the lungs to monitor oxygen levels in air, while a population of neural crest-derived chromaffin cells near the pharyngeal arch arteries was recruited to monitor oxygen levels in blood.

Both sympathoneural and sympathoadrenal systems are involved in the regulation of arterial blood pressure and in the pathogenesis of hypertension. Spontaneously hypertensive rats (SHR), the mostly used animal model of genetic hypertension, is characterized by multiple molecular, morphological and functional alterations at different levels of sympathoneural and sympathoadrenal systems. The study of young prehypertensive SHR allows to reveal the abnormalities preceding hypertension development, whereas adult SHR with established hypertension offers a better model for the treatment of human essential hypertension. The aim of my PhD Thesis was to describe abnormalities in sympathoneural and sympathoadrenal systems in SHR under different conditions. Firstly, ontogenetic differences which might contribute to hypertension development were determined. Secondly, the effect of chemical sympathectomy induced by guanethidine in adulthood on cardiovascular parameters and on the compensatory mechanisms counteracting the reduction of blood pressure were studied. Thirdly, stress-induced cardiovascular response and stress-induced changes of sympathoneural and sympathoadrenal systems were described in adult SHR. My Thesis brought several important results. The increased adrenal catecholamine content and the...

The development of the animal after birth is marked by complex changes. Certain periods are particularly important and have been defined as "critical periods" (Krecek, 1971). Two processes are important to the survival of the animals during these times. The process of "adaptation" involves the maturation of specific physiological systems according to the needs of the neonatal animal, and is dictated by the external environment. The process of "tolerance" renders the neonate relatively unresponsive to a stressor as compared to the adult and protects the animals from over-responding the depleting vital resources until it is physiologically mature. An example of tolerance is the resistance to anoxia of immature neonates. The newborn pig has a high rate of mortality. The number of pigs born 114 days after conception represent only about 55% of the original ova released. Besides having a large number of embryo losses during the gestation period, 13-25% of the live born piglets die before weaning as shown in Table I. The low viability of the neonatal piglets is undoubtedly related to their inability to maintain homeostasis during stress. The sympathetic division of the autonomic nervous system is a major coordinator of homeostasis. Therefore, a study of the development of the sympathetic nervous system could provide some clues to explain the high mortality rate of the newborn pigs. Since the coordinating ability of the sympathetic nervous system is not only dependent on the maturity of the system, but also on the development of the effector organs and their responsiveness to activation, it is logical to examine their relative development.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Tema : Audinių prieinkstinių liaukų histopatologinis tyrimas. Tyrimo objektas: X ūkio 6 mėnesių amžiaus audinių prieinkstinių liaukų histologiniai preparatai. Atlikimo vieta: Lietuvos Sveikatos Mokslų Universiteto Veterinarijos Akademijos Patologijos centras. Darbo apimtis: 41 puslapis, naudoti 43 literatūros šaltiniai, 31 paveikslas. Tyrimo tikslas: Įvertinti audinių prieinkstinių liaukų histomorfologinius pokyčius. Tyrimo uždaviniai: 1. Atlikti histologinį ir histocheminį mėginių tyrimus. 2. Įvertinti audinių prieinkstinių liaukų histopatologijas. Tyrimo metodai: Rutininio skrodimo metu buvo paimta 40 audinių prieinkstinių liaukų pataloginė medžiaga (n=40), fiksuota 10 proc. neutraliu formalino tirpalu, atliktas mėginių dažymas hematoksilinu eozinu ir Kongo raudonuoju. Histologinio tyrimo metu įvertintos prieinkstinių liaukų patologijos. Tyrimo duomenų statistinis įvertinimas atliktas, naudojant Microsoft Exel (2010) programą. Paskaičiuotas įvairių patologijų pasireiškimo dažnumas, jų pasiskirstymas žievėje ir šerdyje (proc.). Taip pat įvertinta, kaip pasiskirstė patologijos žievės zonose, jų pasireiškimo dažnumas procentais. Išvados: 1. Atlikus histologinį tyrimą pakitusių audinių antinksčių rasta 92 proc. 2. Atlikus histocheminį prieinkstinių liaukų tyrimą, baltymo amiloido sankaupų prieinkstinėse liaukose nerasta. 3. Didžiausią dalį patologinių pokyčių sudaro plazmocitų infiltracija (70 proc.) ir hemosiderozė (17 proc.). 4. Mažiausią dalį patologinių pokyčių... [toliau žr. visą tekstą] / Theme: Histopathological research of mink adrenal glands Study object: adrenal gland histological samples (preparations) of 6-month-old minks from farm X. Venue of performance: in Pathology Center of the Veterinary Academy of the Lithuanian University of Health Sciences Volume of the paper: the total volume of the work comprises 41,i.e. 31 picture. The aim of the research: to evaluate histomorphologic changes of mink adrenal glands. Tasks of the work: 1. to make histological and histochemical analysis of samples. 2. to evaluate histopathologies of mink adrenal glands. Research methods: during the routine autopsy was taken pathological material of adrenal glands (n = 40) of 40 minks, which was fixed 10 per cent with neutral formalin solution, and samples dyeing with hematoxylin eosin and Congo red were carried out. Statistical evaluation of the survey data carried out using Microsoft Excel (2010) program. Calculated the frequency of the appearance of various pathologies, their distribution in the cortex and core (in percent). Also, has been assessed the distribution of pathology in cortex areas and their frequency of occurrence percentage (in percent). The most important conclusions : 1. An analysis of 40 male minks adrenal glands histological results showed that 92 per cent. analyzed samples demonstrate a change. 2. The largest part of the pathological changes consist of infiltration by plasmocytes (70 percent.) and hemosiderosis (17 percent.). 3. The smallest part of the... [to full text]