Role of Catecholamines in Regulation of the Functional State of Vasopressinergic Cells of the Rat Hypothalamus

In in vivo and in vitro experiments there have been shown different mechanisms of regulation of hypothalamic vasopressinergic neurons, including regulation due to changes of activity level of brain catecholaminergic and NPY-ergic neurons innervating hypothalamic vasopressinergic cells. We demonstrated in in vitro experiments that dopamine and noradrenaline had no effects on vasopressin expression, but inhibited its release from cell perikarya in supraoptic and paraventricular nuclei of hypothalamus. Besides, activity of vasopressinergic neurons might probably be regulated via activation of synthesis of these neurotransmitters in vasopressinergic cells themselves in the supraoptic and paraventricular nuclei. To activate synthesis of various neurotransmitters, in our case, catecholamines and NPY, in vasopressinergic neurons, different stimuli adequate to trigger or activate synthesis of these substances are required. Synthesis of catecholamines in vasopressinergic cells of supraoptic and paraventricular nuclei was revealed after immobilization stress and adrenalectomy. NPY is synthesized in neurons of hypothalamic neurosecretory centers in norm, and its synthesis increases at disturbances of NPY-ergic innervation of vasopressinergic cells.     

Neurosecretory and microstructural changes in the hypothalamus of rats following administration of lithium chloride and 3H-thymidin

Adult male rats were intraperitoneally administered aqueous solution of lithium chloride (LiCl). Studies, including neurosecretory and microstructural changes within particular neurocytes in supraoptic (NSO) and paraventricular nuclei (NPV) were performed on hypothalamic sections. In the experimental rats the administered LiCl increased the level of GOMORI-positive neurosecretory material both in supraoptic and paraventricular nuclei. Great amounts of the neurosecretory material were markedly conspicuous in the above areas after 20 days of LiCl administration. Investigations carried out on cellular nuclei of particular neurocytes showed a significant enlargement of the nuclei, and statistical calculations revealed that, in comparison with the basic control, the difference was essentially significant (p less than 0.001). 3H-thymidin administration to the rats which had previously been on LiCl for 20 days demonstrated also that within supraoptic nuclei the incorporation of the isotope in cellular nuclei took a faster course than in control animals.     

Morphometric and electron microscopic studies of the secretory granules of neurosecretory cells of the supraoptic and paraventricular nuclei of white rats and mice]

The morphometrical and electron microscopic analysis of secretory granules in the perikaryons of neurosecretory cells of the supraoptic and paraventricular nuclei in male rats and mice has shown than in the cells of these nuclei in both species of animals there occur secretory granules of the same kind and size. Therefore this method fails to determine which of them contain oxytocin and which of them contain vasorpressin. The neurosecretory granules located in the Golgi apparatus zone are of a less size and have more osmiophilic cnetral material than the granules localized on the periphery which mainly have granular central material and are of a greater size. The distinctions in the size and type of secretory granules are associated with certain stages of their "maturation". Granular particles appear to be "swallen", more active forms of storing neurohormones. The presence of larger granular particles in the supraoptic nucleus of mice allows to suggest greater reactivity of this nucleus than in rats which is likely to be associated with a higher ability of mice, as compared with rats, to adaptate to disturbances in water-salt metabolism.     

The implantation of puromycin into the neurosecretory nuclei of the rat

Summary Following the bilateral implantation of puromycin into the paraventricular nuclei of rats, the neurosecretory cells became atrophic and the amount of aldehyde-fuchsin (AF) positive material in the neural lobe decreased. In these rats, urine excretion and water intake increased remarkably. The supraoptic nuclei of the rats were not affected by this treatment. After the unilateral implantation of puromycin in the paraventricular nucleus, the neurosecretory cells of the implanted side became atrophic, while those of the unimplanted side hypertrophied. The neural lobe contained similar amounts of AF-positive material to those of the control rats with unilateral cholesterol implants. In the rats implanted bilaterally with puromycin immediately above the supraoptic nucleus, the neurosecretory cells of this nucleus contained little or no AF-positive material, and urine excretion and water intake increased greatly. The cells of the paraventricular nucleus remained unchanged in these rats.     

Effect of progesterone and estrogens on the state of the hypothalamo-hypophyseal neurosecretory system in pregnancy and labor

Morphofunctional state of the hypothalamo-hypophyseal neurosecretory system was studied in rats at late stages of pregnancy. No special differences both in function of the supraoptical and praventricular nuclei, and in the hypophysis of intact and pregnant rats at administration of progesterone were noted. When estrogenes were administered to pregnant animals, a sharp increase in functioning of the supraoptic and especially of the paraventricular nuclei was noted. The greatest activity of the supraoptic nucleus was observed at delivery that could be resulted from a stress reaction to pain.     

Hypothalamic accessory nuclei and their relation to the angiotensinergic and vasopressinergic systems.

The existence and colocalization of angiotensin II- and vasopressin-like immunoreactivity in individual magnocellular cell groups of the hypothalamus has been demonstrated by using immunocytochemical methods. These neurosecretory magnocellular groups consist of the paraventricular nucleus and the supraoptic nucleus, as well as different accessory cell groups. The fibers from the neurons of the accessory nuclei project directly to adjacent blood vessels and do not comigrate with the hypothalamo-neurohypophysial fiber pathway. On the basis of these findings it can be concluded that in the hypothalamus two different angiotensinergic and vasopressinergic neurosecretory systems exist: (1) an intrinsic hypothalamic and (2) a hypothalamo-neurohypophysial system. The distribution of the accessory cell groups in the hypothalamus is shown in a 3D reconstruction which includes the connection of these magnocellular nuclei with the vascular system in this area.     

Immunocytochemical localization of the vasopressinergic and the oxytocinergic neurons in the human hypothalamus

Summary The human hypothalamic-neurohypophysial hormone-producing nuclei were investigated with the unlabeled antibody peroxidase-antiperoxidase complex (PAP) technique at the light microscopic level. The size, shape and location of the supraoptic, paraventricular, accesssory supraoptic and suprachiasmatic nuclei were determined. It was demonstrated in the human hypothalamus, as well as in the hypothalamus of other mammals, that vasopressin and oxytocin are synthesized in separate neurons. In each of the nuclei of the magnocellular neurosecretory system, the distribution, ratios and structural features of the vasopressinergic and oxytocinergic neurons were determined. It was shown that the human suprachiasmatic nuclei contain numerous neurophysin-vasopressin-producing neurons.This investigation was supported by a grant from the Belgian Nationaal Fonds voor Geneeskundig Wetenschappelijk Onderzoek     

Development of oxytocin- and vasopressin-network in the supraoptic and paraventricular nuclei of fetal sheep

The hypothalamic supraoptic and paraventricular nuclei consist of oxytocin and arginine vasopressin synthesizing neurons that send projections to the neurohypophysis. A growing body of evidence in adult animals and young animals at near term confirmed the structure and function in the vasopressinergic and oxytocinergic network. However, whether those distinctive neural networks are formed before near term is largely unknown. This study determined the special patterns in location and distribution of oxytocin- and vasopressin-neurons in the paraventricular and supraoptic nuclei from preterm to term in the ovine fetuses. The results showed that oxytocin- and vasopressin-neurons were present in both nuclei at the three gestational time periods (preterm, near term, and term). In the paraventricular nuclei, vasopressin-cells concentrated mainly in the core of the middle magnocellular paraventricular nuclei, and oxytocin-cells were scattered surrounding the core. In the supraoptic nuclei, vasopressin-cells mostly located in the ventral part, and oxytocin-cells in the dorsal part. The data demonstrated that the special distributed patterns of vasopressin- and oxytocin-neuron network have formed in those two nuclei at least from preterm. Intracerebroventricular injection of angiotensin II significantly increased fetal plasma oxytocin and vasopressin levels at preterm, which was associated with an increase of oxytocin- and vasopressin-neuron activity marked with c-fos expression. The data provided new evidence for the structural and functional development of the oxytocin- and vasopressin-network before birth.     

Functional changes in neurosecretory cells of the anterior hypothalamic nuclei after stimulation of the midbrain reticular formation

The functional activity of the neurosecretory cells in the supraoptic and paraventricular nuclei was studied in male Wistar albino rats at various intervals after electric stimulation of the midbrain reticular formation. These studies showed that such stimulation elicits higher functional activity of the neurosecretory cells in the anterior hypothalamic nuclei, characterized by increased secretory synthesis by these cells and rapid transport of the neurosecretion. These changes were most pronounced 1 h after stimulation of the reticular formation. The changes observed were unidirectional in both neurosecretory centers, but their manifestation was different: in the supraoptic nucleus the reaction was more intense but short lived, in the paraventricular it was less intense but lasted longer.A. A. Bogomolets Institute of Physiology, Academy of Sciences, Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 3, No. 4, pp. 394–400, July–August, 1971.     

Vasopressinergic axon collaterals and axon terminals in the magnocellular neurosecretory nuclei of the rat hypothalamus

Axon collaterals emerging from the vasopressinergic neurons of the supraoptic (SON) and paraventricular (PVN) nuclei and recurving back towards their respective nuclei have been previously reported. Since such axon collaterals can play a role in the neuromodulation of SON and PVN, these nuclei have been further investigated immunohistochemically under the light and electron microscope. The PAP technique, using a commercial antibody, was employed. Vasopressin-positive axon collaterals were seen to recurve towards their nuclei of origin. In the latter, vasopressinergic intrinsic neurons were also observed. Under the electron microscope, axon terminals containing vasopressin-immunoreactive neurosecretory granules were noted. Such terminals presumably arise from the vasopressin-positive recurrent axon collaterals or from the intrinsic neurons for the purpose of neuromodulation within the SON and PVN.     

Immunocytochemistry of magnocellular neurons of supraoptic and paraventricular nuclei of normal and Brattleboro rats with vasopressin anti-idiotype antibody

Summary A vasopressin anti-idiotype antibody was generated by immunization with purified IgG of a primary vasopressin antiserum. The anti-idiotype antibody immunostained neurons in the supraoptic and paraventricular nuclei of the hypothalamus of normal and Brattleboro rats. The distribution of immunostained perikarya in these hypothalamic nuclei together with the staining of fibers in median eminence and neural lobe was similar to that observed in normal rats with anti-vasopressin and suggests strongly that vasopressinergic neurons are being stained. Absorption studies with vasopressin and a vasopressin-binding receptor protein further indicate that a receptor associated with vasopressinergic neurons is recognized by the anti-idiotype antibody.Supported by NIH grants ES03239, NS18626 and NSF grant BNS-8310914. D.T.P. is the receipient of RCDA award NS00869     

The topography of Gomori positive neurosecretory elements of the hypothalamus of the lemmings Dicrostonyx torquatus and Lemmus sibiricus]

Under study was the structure of the hypothalamo-hypophyseal neurosecretory system in two species of lemmings of the Wrangel island: the collared lemming, (Dicrostonyx torquatus) and the Ob lemming (Lemmus sibiricus). Inspite of the similarity in the general organization of this system in all rodents, certain species features were found in the topography of neurosecretory elements in the animals studied. In the Ob lemming there is a great similarity in the structures of the neurosecretory system with the albino rat than in the collared lemming. In both species of lemmings, and in the collared lemming in particular, the supraoptic nucleus is located more dorso-caudally and the paraventricular one-more dorsally. A greater amount of neurosecretory cells is found which from additional groups. The hypothalamo-hypophyseal and extrahypothalamic pathways are well pronounced. The postoptical nucleus is considerably developed. In the collared lemming it is almost equal to the supraoptic one in the amount of cells composing it. The ratio of the cells in the supraoptic and postoptic nuclei is suggested to be related to the level of the water-salt metabolism and the specific ecology of lemmings.     

Changes in metabolic activity of neurons in the anterior hypothalamus nuclei during hyperthermia, fever, and hypothermia

Differently directed changes in metabolic activity of anterior hypothalamic nuclei's neurons in rats during hyperthermia, fever, and hypothermia were revealed with histochemical methods. During hyperthermia, the activity of energy metabolism enzymes increased as well as RNA content in the neurons of supraoptic, paraventricular and median preoptic anterior hypothalamic nuclei. This is shown by an increase in the metabolic activity of neurons of these nuclei. Metabolic activity in neurons of median preoptic nuclei decreased and was not changed considerably in neurons of supraoptic and paraventricular nuclei during endotoxin-induced fever. The development of hypothermia was characterised by a decrease in metabolic activity of neurons of supraoptic, paraventricular and medium preoptic nuclei. It is supposed that differently directed metabolic activity changes in neurons of anterior hypothalamic nuclei during hyperthermia are connected with the mechanisms of body temperature regulation (median preoptic nuclei) and neurosecretory processes (supraoptic and paraventricular nuclei).     

Immunocytochemical demonstration of separate vasopressin-neurophysin and oxytocin-neurophysin neurons in the human hypothalamus

Summary With the use of immunocytochemistry, it was shown that both the supraoptic and paraventricular hypothalamic nuclei in humans contain at least two different neurophysins. These two human neurophysins are immunologically related to bovine neurophysin I and neurophysin II, respectively. One human neurophysin is associated with vasopressin, the other with oxytocin. Human vasopressin-neurophysin and oxytocin-neurophysin are located separately in two different types of neurons, which correspond respectively to the vasopressinergic and oxytocinergic neurons of both the supraoptic and paraventricular nuclei. The neurophysin of the human vasopressinergic suprachiasmatic neurons appears to be closely related to or identical with neurophysin of the vasopressinergic neurons of the human magnocellular hypothalamic nuclei.This investigation was supported by a grant from the Belgian Nationaal Fonds voor Geneeskundig Wetenschappelijk Onderzoek     

CHANGES IN THE HYPOTHALAMO-NEUROHYPOPHYSICAL NEURO-SECRETORY MATERIALS OF RATS DURING DIFFERENT PHASES OF MORPHINE ADMINISTRATION

Abstract—

• 1 Acute morphine treatment of rats increased the concentration of neuro-secretory material in the posterior pituitary. These changes were accompanied by the presence of more neurosecretory materials in the axons of the hypothalamic supraoptic and paraventricular neurons and in the hypothalamic capillaries and sinuses. In the perikarya of the hypothalamic supraoptic and paraventricular neurons, the neurosecretory material is in a dispersed state.
• 2 Following chronic morphine treatment, neurosecretory material was almost absent from the posterior pituitary, whereas in the perikarya of the supraoptic and paraventricular neurons, congestion of neurosecretory material is observed which is accompanied by the absence of the neurosecretory material from the axons arising from the supraoptic and paraventricular nuclei and from the hypothalamic capillaries and sinuses.
• 3 During nalorphine-induced abstinence, there was sudden reappearance of the neurosecretory material in the posterior pituitary along with the appearance of neurosecretory material in the hypothalamic neurosecretory neuronal tracts, blood capillaries and sinuses together with the dispersion of the neurosecretory materials from the hypothalamic neurosecretory neurons.

     

Proliferation and differentiation of nerve cells of the human NN. supraopticus et paraventricularis transplanted to the brain of adult rats]

Human fetal hypothalamic neurosecretory cells (NSC) were studied after transplantation into the third ventricle of the adult rat brain. 3H-thymidine uptake data have shown that the time of origin and proliferation of NSC of grafted tissue and of supraoptic and paraventricular nuclei in normal embryogenesis was similar. Specific staining revealed that the start of neurosecretory function in grafted tissue corresponded to the date when NSC began functioning in normal ontogenesis.     

Pressor response to l-cysteine injected into the cisterna magna of conscious rats involves recruitment of hypothalamic vasopressinergic neurons

The sulfur-containing non-essential amino acid l-cysteine injected into the cisterna magna of adult conscious rats produces an increase in blood pressure. The present study examined if the pressor response to l-cysteine is stereospecific and involves recruitment of hypothalamic vasopressinergic neurons and medullary noradrenergic A1 neurons. Intracisternally injected d-cysteine produced no cardiovascular changes, while l-cysteine produced hypertension and tachycardia in freely moving rats, indicating the stereospecific hemodynamic actions of l-cysteine via the brain. The double labeling immunohistochemistry combined with c-Fos detection as a marker of neuronal activation revealed significantly higher numbers of c-Fos-positive vasopressinergic neurons both in the supraoptic and paraventricular nuclei and tyrosine hydroxylase containing medullary A1 neurons, of l-cysteine-injected rats than those injected with d-cysteine as iso-osmotic control. The results indicate that the cardiovascular responses to intracisternal injection of l-cysteine in the conscious rat are stereospecific and include recruitment of hypothalamic vasopressinergic neurons both in the supraoptic and paraventricular nuclei, as well as of medullary A1 neurons. The findings may suggest a potential function of l-cysteine as an extracellular signal such as neuromodulators in central regulation of blood pressure.     

Activation of vasopressinergic and oxytocinergic neurons during aging in the Wistar rat

The activity of the hypothalamo-neurohypophyseal system (HNS) was determined in male Wistar rats from 3 to 32 months of age. Plasma levels of vasopressin (AVP) and oxytocin (OXT) were measured by means of a radioimmunoassay. In addition, the distribution of the Golgi apparatus marker enzyme thiamine-pyrophosphatase (TPP-ase) was measured as a parameter for neurosecretory activity in the hypothalamic supraoptic and paraventricular nuclei (SON and PVN). Plasma levels of radioimmunoassayable AVP were increased in the 32-month-old animals. Plasma levels of radioimmunoassayable OXT in 32-month-old animals did not differe from the levels found in the youngest group, but were higher than in 11-month-old animals. Neurosecretory activity in the SON was similar in 3- and 32-month-old animals, whereas in the PVN neurosecretory activity was increased in the 32-month-old animals. Urine excretion decreased between 6 and 11 months of age and remained on the same level until 32 months of age. In other words, instead of a loss of HNS function as has been suggested in the literature, an increased neurosecretory activity was observed in aged rats.     

Cholinesterase activity of the hypothalamo-hypophysial neurosecretory system in rats during the ontogenetic development

Summary The hypothalamic region and the neural lobe of rats from the 16th foetal day to adult animals have been studied for acetylcholinesterase and cholinesterase activity after Karnovsky. The attention was focused on the magnocellular nuclei-supraoptic and paraventricular, the median eminence and the neural lobe. Acetylcholinesterase activity appears in the paraventricular nucleus on the 18th foetal day, i.e. prior to that in the supraoptic nucleus. Heterochronic development and heteromorphism of paraventricular neurosecretory cells have been noticed. The median eminence shows no clear acetylcholinesterase activity. There are acetylthiocholine and butyrylthiocholine positive structures in the posterior pituitary. These structures are especially pronounced in 30–47-day rats. The cholinergic mechanism of release of neurohormones from the neural lobe is suggested. The results are discussed in functional and phylogenetic aspects.     

Cytologie du lobe anterieur de l'hypophyse du chien

Summary Detailed histochemical studies have been made on the distribution of various enzymes such as phosphatases, cholinesterases, glycolytic enzymes and respiratory enzymes in various components of the hypothalamus with special reference to the supraoptic and paraventricular nuclei of the Squirrel Monkey. Cytological studies have also been made by the McManus, Einarson, Gomori and Bargmann methods.A few neurons of these nuclei showed scanty Gomori-positive material in the cytoplasm for the Gomori and Bargmann methods. Nissl granules were located in the peripheral cytoplasm of most neurons. No glycogen granules were observed in these neurons. For these reasons, the Squirrel Monkey, like the rat, may not be a suitable species for the study of neurosecretory phenomena.The axons of these neurons were negative for the specific cholinesterase test, though the perikaryon and some parts of the processes gave a moderately positive reaction. These neurons may be non-cholinergic and the cholinergic fibers from an unknown nucleus may end in synapses on their cell bodies. Blood vessels and glial cells in the neurosecretory nuclei showed non-specific cholinesterase activity. This enzyme may hydrolyze the acetylcholine which has escaped splitting by specific cholinesterase. Alkaline phosphatase and acid phosphatase in these neurons may be involved in the metabolism concerned with the production of neurosecretory material. The neurons may be physicochemical receptors and may get enough energy and raw material to synthesize the neurosecretory material from the rich blood supply. Neurons of the supraoptic and paraventricular nuclei as well as other hypothalamic neurons, like neurons of other regions of the brain, are well equipped with the enzymes of the glycolytic pathways and the tricarboxylic acid cycle. Since the glial cells of these nuclei have amylophosphorylase activity and glycolytic pathways, they may work as energy donators to the neurons of the neurosecretory nuclei. T. R. Shanthaveerappa in previous publications.