On degeneration of peptidergic neurosecretory fibres in the albino rat

Three types of degenerating peptidergic neurosecretory fibres have been found in the posterior pituitary of chronically dehydrated albino rats. "Dark" neurosecretory fibres and their swellings contain neurosecretory granules, neurotubules, shrunken mitochondria and diffusely distributed fine dense material. Some swellings are filled with synaptic vesicles and/or conglomerations of dense membranes. The transitional forms exist between these fibres and extracellular accumulations of electron dense material. Synaptic vesicles, single neurosecretory granules, lipid-like droplets and lamellar bodies occur in the latter. Some neurosecretory fibres and swellings have numerous polymorphous inclusions arising due to degradation of secretory inclusions and organelles, mitochondria and neurotubules in particular. "Dark" neurosecretory elements and those with numerous polymorphous inclusions are enveloped by pituicyte cytoplasm. Sometimes the plasma membranes both of the pituicytes and neurosecretory fibres are destroyed or transformed into a multi-membrane complex. It is assumed that pituicytes may phagocytize degenerating neurosecretory elements. N urosecretory fibres with a locally dissolved neuroplasm and/or large lucent vacuoles seem to be due to axonal degeneration by the "light" type. These neurosecretory elements, the largest of them in particular, may transform into large cavities bordered by a membrane and containing flake-like material and single-membrane vacuoles. Degeneration of neurosecretory elements seems to occur mainly due to hyperfunction of the hypothalamo-hypophysial neurosecretory system.     

Influence of Catecholamines on Migration and Differentiation of GnRH Neurons in Rats

The GnRH producing neurons are the key link of neuroendocrine regulation of the adult reproductive system. Synthesis and secretion of GnRH are, in turn, under the afferent catecholaminergic control. Taking into account that catecholamines exert morphogenetic effects on target cells during ontogenesis, this study was aimed at investigation of the effects of catecholamines on development of GnRH neurons in rats during ontogenesis. We carried out comparative quantitative and semiquantitative analyses of differentiation and migration of GnRH neurons in fetuses of both sexes under the conditions of normal metabolism of catecholamines (administration of saline) or their pharmacologically induced deficiency (administration of -methyl-para-tyrosine). The inhibition of catecholamine synthesis from day 11 of embryogenesis led to an increasing number of GnRH neurons in rostral regions of the trajectory of their migration over the brain: in the area of olfactory tubercles on day 17 and in the area of olfactory bulb on days 18 and 21. In addition, the optical density of GnRH neurons located in the rostral regions of migration was higher in the fetuses after administration of -methyl-para-tyrosine during embryogenesis, as compared to the control. It has been concluded that catecholamines stimulate the migration of GnRH neurons and affect their differentiation.     

Developing Brain as an Endocrine Organ: A Paradoxical Reality

The maintaining of homeostasis in the organism in response to a variable environment is provided by the highly hierarchic neuroendocrine-immune system. The crucial component of this system is the hypothalamus providing the endocrine regulation of key peripheral organs, and the adenohypophysis. In this case, neuron-derived signaling molecules (SM) are delivered to the blood vessels in hypothalamic “neurohaemal organs” lacking the blood–brain barrier (BBB), the posterior lobe of the pituitary and the median eminence. The release of SM to the blood vessels in most other brain regions is prohibited by BBB. According to the conventional concept, the development of the neuroendocrine system in ontogenesis begins with the “maturation” of peripheral endocrine glands which first are self-governed and then operate under the adenohypophysial control. Meantime, the brain maturation is under the control of SM secreted by endocrine glands of the developing organism and coming from the placenta and maternal organism. The hypothalamus is involved in the neuroendocrine regulation only after its full maturation that is followed by the conversion of the opened-looped neuroendocrine system to the closed-looped system as in adulthood. Neurons of the developing brain begin to secrete SM shortly after their origin and long before the establishment of specific interneuronal relations providing initially autocrine and paracrine morphogenetic influence on differentiating target neurons. Taking into account that the brain lacks BBB over this ontogenetic period, we hypothesized that it operates as the multipotent endocrine gland secreting SM to the general circulation and thereby providing the endocrine regulation of peripheral organs and the brain. The term “multipotent” means that the spectrum of the brain-derived circulating SM and their occupancy at the periphery in the developing organism should greatly exceed those in adulthood. In order to test this hypothesis, gonadotropin-releasing hormone (GnRH), dopamine (DA), and serotonin (5-hydroxytryptamine, 5-HT) were chosen as the markers of the presumptive endocrine function of the brain in ontogenesis. According to our data, the concentrations of GnRH, DA, and 5-HT in the rat general circulation during the perinatal period, i.e. before the establishment of BBB, was as high as those in the portal circulation in adulthood. The concentrations of circulating GnRH and DA dropped to almost undetectable level after the development of BBB suggesting their brain origin. This suggestion has been proven by showing an essential decrease of GnRH, DA, and 5-HT concentrations in general circulation of perinatal rats after microsurgical elimination of synthesizing neurons or the inhibition of specific syntheses in the brain before the establishment of BBB. GnRH, DA, and 5-HT apparently as dozens of other brain-derived SM appear to be capable of providing the endocrine influence on their peripheral targets like the adenohypophysis, gonads, kidney, heart, blood vessels, and the brain (endocrine autoregulation). Although the ontogenetic period of the brain operation as the multipotent endocrine gland is relatively short, the brain-derived SM are thought to be capable of providing long-lasting morphogenetic effects on peripheral targets and the brain. Thus, the developing brain operates as the multipotent endocrine gland from the onset of neurogenesis to the establishment of BBB providing the endocrine regulation of the developing organism.     

Expression of tyrosine hydroxylase in vasopressinergic neurons of the supraoptic nucleus in rat ontogenesis and its modulation by noradrenergic afferents

An attempt is made to find out, at what stage of ontogenesis an expression of gene and synthesis of tyrosine hydroxylase (TH) is started, and whether noradrenergic afferents participate in regulation of these processes. The study is carried out on rats at the 21st embryonal day (E21), P3 and P13 with use of quantitative and semi-quantitative immunocytochemistry and hybridization in situ. Animals of all ages were subjected to a salt load, in some cases on the background of introduction of and α1-adrenoreceptor inhibitor, prazozine. According to the obtained data, the TH expression in SON neurons in response to the salt load begins at P3. The number of VP-ergic neurons expressing TH during the salt load is 3-fold reduced from P3 to P13. Taking into account that the innervation of VP-ergic SON neurons is realized for this period of development, we formulated a hypothesis that the TH expression is inhibited by noradrenergic afferents. According to the obtained data, TH is not expressed in osmotically stimulated VP-ergic neurons on the background of prazozine injection at E21; however, this combined effect results in increased TH expression at P3 and P13. At P13, i.e., in animals with a more developed afferent innervation, the amount of TH-immunoreactive neurons is three times lower, than at P3. Thus, in ontogenesis of rats, VP-ergic neurons begin to respond to osmotic stimulation by inclusion of the TH gene expression and its synthesis at the neonatal period, the both processes being under the inhibitory control of noradrenergic afferents mediated through α1-adrenoreceptors.     

Gene expression of proteins of the vesicle cycle in the striatum and motor cortex under functional failure of nigrostriatal system

Degeneration of dopaminergic neurons in the substantia nigra and the decrease in the dopamine level in the striatum lead to dysfunctions of motor behavior. This is accompanied by dysregulation of neuro-transmission in glutamatergic neurons of the motor cortex and GABA-ergic neurons of the striatum. It is shown that dysregulation of the gene expression of vesicle cycle proteins in neurons of the motor cortex occurs at an early (presymptomatic) stage of degeneration of the nigrostriatal system, and in more severe degeneration (symptomatic stage) the level of gene expression of vesicle cycle proteins in the striatum decreases.     

CSF-contacting epithelia in altered gravity: changes in apical structures and water channels expression

Apical cytoskeletal structures and water channels are affected in both choroidal and ependymal cells lining the cerebral ventricles. Structural alterations and changes in expression of AQPI and AQP4, evaluated by immuno-cytochemistry and in situ hybridization confirm the impact of variations in gravity in CSF-lining epithelia.     

Differentiation of Magnocellular Vasopressinergic Neurons and Its Regulation by Signal Molecules in Ontogenesis

An analysis is presented of the literary data on differentiation of magnocellular vasopressinergic (VPergic) neurons and their regulation by signal molecules in ontogenesis. The VPergic neurons are formed in ontogenesis from cells-precursors of the III ventricle wall; after that, they migrate first into the supraoptic nucleus and then into the paraventricular and accessory nuclei of hypothalamus. At the migration period or at once after migration of the neurons a gene expression and synthesis of preprovasopressin (prepro-VP) occurs. The enzymatic processing of prepro-VP with a formation of functionally active VP begins somewhat later than synthesis of preprohormone. Axons of the VPergic neurons reach the posterior lobe of pituitary before or at once after migration of the neurons into the magnocellular nuclei. Much later, at the perinatal period, the mechanisms of VP release from axons into the general circulation are formed. At the end of prenatal period, the neurons start responding to functional stimulation by an increase of synthesis of the prepro-VP mRNA and peptide itself, as well as by expression of the tyrosine hydroxylase after birth. Differentiation of the VPergic neurons is affected by a short-term or long-term (imprinting) action of catecholamines, neuropeptides, and several hormones of endocrine glands.