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[Correlation between the brain serotonin and the hypothalamic neuro-secretion in rat (author's transl)].

Parenteral administration of PCPA (200 mg/kg) induces changes in the quantitiy and the distribution of hypothalamic neurosecretion. This action appears very quickly and increases during the 48 hours following the injection. The histologic observations disclose a large accumulation of neurosecretory material in the supraoptic nuclei and in the accessory magnocellular groups of the anterior hypothalamus. In the median eminence large Herring bodies are seen. These results are to be compared to those obtained after mesencephalic raphes lesioning. The histologic alterations observed in the anterior hypothalamic level, may be due to complex disturbances involving the monoaminergic neuromediation.

Animals↗

[Calcified bladder oat cell associated with hypercalcemia and hypophosphoremia].

Description of a 69-year old male patient presenting calcified vesical tumour which, following a pathoanatomical study was shown to be an non-differentiated oat cell carcinoma associated to transitional carcinoma and adenocarcinoma. Biochemically it presented hypercalcemia and hypophosphoremia and the electron microscope study demonstrated the presence of neurosecretion granules. The immunohistochemical techniques were negative for protein S-100 and cytokeratins, but positive for the membrane epithelial antigen and the neuro-specific enolase. The patient was treated by transurethral resection and polychemotherapy, presenting an initially favourable response but dying 18 months later after widespread metastasis. These data are in agreement with those obtained from the literature review carried out with regard to clinical picture, pathoanatomical studies, aggressiveness and overall poor prognosis with this type of tumours. In our view, the tumour's mixed composition supports an origin of pluripotential cell (steam cell). Presence of neuroendocrine syndromes associated to oat cell vesical tumours is an unusual fact related to the tumour's hormonal secretion.

Adenocarcinoma↗

Nicotinic receptor-evoked release of acetylcholine and somatostatin in the myenteric plexus is coupled to calcium influx via N-type calcium channels.

Entry of extracellular calcium (Ca++) via voltage-gated Ca++ channels is essential for neurotransmitter release. In this study, we examined whether nicotinic receptor-stimulated release of acetylcholine (ACh) and somatostatin (S14) are coupled to calcium influx via distinct calcium channel subtypes in the myenteric plexus. Isolated ganglia from the guinea pig ileal myenteric plexus were prepared and placed in perfusion chambers under standard conditions. The ganglionic agonist dimethylphenylpiperazinium (DMPP, 10(-6) to 10(-3) M) stimulated the release of [3H]ACh in a concentration-dependent manner. This release was blocked by hexamethonium or Ca(++)-free medium containing 1 mM EGTA and was antagonized by omega-conotoxin, a preferential N calcium channel blocker, but was not affected by nifedipine (L channel antagonist) or nickel (T calcium channel antagonist). DMPP-evoked release of somatostatin was also antagonized by omega-conotoxin, but was not affected by nifedipine or nickel. These observations indicate that neurosecretion of ACh and S14 evoked by DMPP is mediated by calcium entry via voltage-sensitive N-type Ca++ channels. To provide additional evidence that nicotinic receptor stimulation is associated with Ca++ entry via the N-type Ca++ channels, we examined the intracellular calcium [Ca++]i concentration of the myenteric plexus neurons using fura-2 microspectrofluorometry. Basal [Ca++]i of single ileal myenteric neurons was 65 +/- 5 nM. Perfusion with DMPP (10(-6) to 10(-3) M) caused a rapid, transient elevation in [Ca++]i which was abolished by Ca(++)-free medium containing 1 mM EGTA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

[Electron-cytochemical distribution of acetylcholinesterase, monamine oxidase and Mg2+-ATPase in the human hypothalamus].

The distribution of acetylcholinesterase, monoaminoxidase and ATP-ase was studied in human hypothalamus by means of electron microscopy. The study demonstrated a possibility of differentiation of the hypothalamic neurons according to phases of neurosecretion. These data were achieved on the basis of electron cytochemistry in detecting ATP-asa in the nuclei of neurons. Comparing literary data concerning the nonmediator role of acetyl-choline and catecholeamines with personal studies, the authors demonstrate the internal and external barrier functions of acetylcholinesterase and monoamineoxidase in the brain.

Acetylcholinesterase↗

Circadian gene expression regulates pulsatile gonadotropin-releasing hormone (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1-7 cell line.

Although it has long been established that episodic secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus is required for normal gonadotropin release, the molecular and cellular mechanisms underlying the synchronous release of GnRH are primarily unknown. We used the GT1-7 mouse hypothalamic cell line as a model for GnRH secretion, because these cells release GnRH in a pulsatile pattern similar to that observed in vivo. To explore possible molecular mechanisms governing secretory timing, we investigated the role of the molecular circadian clock in regulation of GnRH secretion. GT1-7 cells express many known core circadian clock genes, and we demonstrate that oscillations of these components can be induced by stimuli such as serum and the adenylyl cyclase activator forskolin, similar to effects observed in fibroblasts. Strikingly, perturbation of circadian clock function in GT1-7 cells by transient expression of the dominant-negative Clock-Delta19 gene disrupts normal ultradian patterns of GnRH secretion, significantly decreasing mean pulse frequency. Additionally, overexpression of the negative limb clock gene mCry1 in GT1-7 cells substantially increases GnRH pulse amplitude without a commensurate change in pulse frequency, demonstrating that an endogenous biological clock is coupled to the mechanism of neurosecretion in these cells and can regulate multiple secretory parameters. Finally, mice harboring a somatic mutation in the Clock gene are subfertile and exhibit a substantial increase in estrous cycle duration as revealed by examination of vaginal cytology. This effect persists in normal light/dark (LD) cycles, suggesting that a suprachiasmatic nucleus-independent endogenous clock in GnRH neurons is required for eliciting normal pulsatile patterns of GnRH secretion.

ARNTL Transcription Factors↗

[Neurobiology of depression and stress syndromes. Focus on active neurosteroids and neurosteroids].

That the brain is a target for hormones is a well established fact. Today we also know that brains can secrete the whole gamut of peptides and steroid hormones, i.e., pregnanes and pregnenes. Considering that the ancestral neuron was a neurosecreting cell, this is not surprising. As CRH and cortisol secretion occur in situ in nervous systems, the intriguing possibility that anxio-depressive syndromes may be associated with paracrine effects of these compounds on the brain should now be considered. The concept of stress as a specific reaction of the nueroendocrine system to nocuous stimuli is re-examined in light of new evidence. The fundamental importance of historical, social, and psychological contexts in evaluating hormonal actions is emphasized. Problems emerging from the attempt to search for specific biological markers in different psychiatric disorders are discussed. The suggestion is made that, rather than to categorize nosological entities, biological dysfunctions should be elated with psychological abnormalities.

Anxiety↗

Burst activity and synaptic mechanisms in a hypothalamic network grown in culture.

In a cultured network of rat embryonic hypothalamic cells, synaptic interaction is through GABAA-receptors, that mediate inhibition by an increase in Cl- conductance, and AMPA-receptors, that mediate excitation by an increase in monovalent cationic conductance. Changes in the balance of inhibition and excitation towards a predominance of excitation lead to phasic synchronous activity of the cells. Synaptic interaction through these receptors is thus capable of modulating neurosecretion rapidly.

Action Potentials↗

[Biochemical and histological changes in the hypothalamus in hormone-stimulated sheep].

The effects were investigated of a hormonal preparation of serum gonadotrophin (SC) on neurosecretion, PAS-positive mucopolysaccharides and on histological changes in the third cerebral ventricle; at the same time variations were determined of catecholamine concentrations of ependyma surface in the hypothalamic regions that control directly reproductive functions in ewes of the Merino and Wallachian breeds in the oestrus period. Ewe oestrus was synchronized by insertion of Ageline (Spofa) sponges into the vagina. A dose of 2000 IU of serum gonadotrophin (Bioveta, Ivanovice in Haná) was administered to stimulate the ewes (n = 30). Twelve ewes of the Wallachian breed, six control and six test ones, were used for radioenzymatic detection of catecholamines (Catechola test, Prague). The brains were segmented immediately after bleeding and samples were taken from the eminentia medialis, area preoptica and corpus mamillare pursuant to the stereotactic configuration of the sheep hypothalamus (Welento et al., 1968). The brains of ten ewes of the Merino breed, four control and six test ones, and of eight ewes of the Wallachian breed (four control and four test ones) were used for histological treatment. For the purposes of a histological study, the brains were treated with current histological methods. The amount of neurosecretory material was assessed by light microscopy (Nakahara, 1963). Samples for the study of ependyma of the lower part of the third cerebral ventricle were examined in a scanning electron microscope. The obtained results demonstrate a statistically significant decrease by 36.4% (P less than 0.05) in epinephrin concentrations in the area preoptica of hypothalamus after SG administration (Fig. 3), in comparison with the control group. A decrease in norepinephrin concentration in the corpus mamillare (Fig. 4) was statistically significant (P less than 0.001). The dose of 2000 IU SG influenced most markedly catecholamine concentrations in the eminentia medialis (Fig. 5), where a statistically significant decrease in epinephrin and norepinephrin concentration was observed (P less than 0.01). Dopamine concentrations also decreased significantly (P less than 0.05) in the eminentia medialis (Fig. 5). Following the hormonal stimulation, a significant increase in dopamine and epinephrin concentrations was observed in the hypophysis of sheep (Fig. 6; P less than 0.05) and in the epiphysis there was a significant decrease in epinephrin and dopamine concentration (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A central role for oxygen-sensitive K+ channels and mitochondria in the specialized oxygen-sensing system.

Mammals possess a specialized O2-sensing system (SOS), which compensates for encounters with hypoxia that occur during development, disease, and at altitude. Consisting of the resistance pulmonary arteries (PA), ductus arteriosus, carotid body, neuroepithelial body, systemic arteries, fetal adrenomedullary cell and fetoplacental arteries, the SOS optimizes O2-uptake and delivery. Hypoxic pulmonary vasoconstriction (HPV), a vasomotor response of resistance PAs to alveolar hypoxia, optimizes ventilation/perfusion matching and systemic pO2. Though modulated by the endothelium, HPV's core mechanism resides in the smooth muscle cell (SMC). The Redox Theory proposes that HPV results from the coordinated action of a redox sensor (proximal mitochondrial electron transport chain) which generates a diffusible mediator (a reactive O2 species, ROS) that regulates effector proteins (voltage-gated K(v) channels). Hypoxic withdrawal of ROS inhibits K(v)1.5 and K(v)2.1, depolarizes PASMCs, activates voltage-gated Ca2+ channels, increasing Ca2+ influx and causing vasoconstriction. Hypoxia's effect on ROS (decrease vs. increase) and the molecular origins of ROS (mitochondria vs. NADPH oxidase) remains controversial. Distal to this pathway, Rho kinase regulates the contractile apparatus' sensitivity to Ca2+. Also, a role for cADP ribose as a redox-regulated mediator of intracellular Ca2+ release has been proposed. Despite tissue heterogeneity in the SOS's output (vasomotion versus neurosecretion), O2-sensitive K+ channels constitute a conserved effector mechanism. Disorders of the O2-sensing may contribute to diseases, such as pulmonary hypertension.

Animals↗

[Morphofunctional characteristics of neurosecretory cells of the supraoptic nucleus of rats with parathyroprival hypocalcemia].

Humori-positive neurosecretory cells of the supraoptic nucleus of the hypothalamus have been investigated during various time of parathyroprival hypocalcemia after extirpation of the parathyroid glands. Contents of total and ionized calcium, phosphorus in blood serum have been estimated. Volume of nuclei and nucleoli has been measured. In 5 days functional activity of the supraoptic nucleus increases (lightly stained cells predominate, volume of the nuclei and nucleoli increases). In subsequent 15-30 days its activity decreases (increase in amount of dark-stained cells, nucleolar volume decreases). In 60 days there is a tendency to restoration of neurosecretion.

Animals↗

["Fenaf"--a new histochemical stain].

The authors have synthesized a new dye which by its histochemical properties is analogous to the imported aldehyde-fuchsin but much cheaper. The production of this dye under the trade name "Fenaf" is organized at Shostka's factory of chemicals. The dye reveals neurosecretion, thyrothrophocytes of the adenohypophysis, tissue mast cells and other structures that are stained with aldehyde-fuchsin.

Autopsy↗

[The endocrine hypothalamus].

Existing data on the peptide hormones in connection with the hypothalamus topography, close interrelationship in the vegetative brain centre of a number of specialized neuronal nuclei with unknown hormonal activity give an example of a highly developed system of the homeostatic function regulation. The author's concept of the neurosecretion mechanism is presented.

Animals↗

[Intracerebral gangliocytoma: a histological and immunohistochemical study].

We present a case of cerebral gangliocytoma placed on the right frontal lobe in a young adult, analyzing its morphological and clinical features. The immunohistochemical study defines it as a tumor with a neuronal population NSE and NFP positive, and a glial population with positivity for the GFAP. We emphasize the presence of neurosecretion in the mature neurones, typified by the positivity to the sinaptophisine and VIP. In the discussion we compare our immunohistochemical results, analyzing the histogenesis of this rare neoplasm.

Adult↗

Synaptic vesicle ceramide kinase. A calcium-stimulated lipid kinase that co-purifies with brain synaptic vesicles.

Much current work on the mechanism of neurosecretion has focused on proteins specific to neural secretory vesicles (synaptic vesicles). We report a calcium-stimulated lipid kinase that co-purifies with rat brain synaptic vesicles. This enzyme activity is found only in membrane fractions that contain synaptic vesicle markers. Based on identification of the lipid product as ceramide 1-phosphate and on the finding that ceramide kinase activity co-purifies with synaptic vesicles, the enzyme is proposed to be a ceramide kinase. Kinase activity is stimulated by micromolar concentrations of calcium. Calcium increases the apparent Vmax of the reaction with little effect on the Km for ceramide. The vesicular localization of this enzyme, the requirement for ATP, and the stimulation of enzyme activity by micromolar calcium suggest that ceramide phosphorylation may be associated with neurotransmitter release.

Animals↗

Recent development in hormone research.

A classical distinction between endocrine cells and neurons cannot be accepted without exception. This dichotomy was first challenged by the concept of neurosecretion. Recent observations indicate that hormone synthesis takes place in many extraendocrine tissues since the gene expression for prohormone synthesis seems to be common for all eukaryotes although the secretion of biological active hormone products is limited by posttranslational processing for differentiated cells. Increasing number of data support the view that regulation of pituitary hormone secretion is under multifactorial control in addition to specific signaling molecular effects of hormone-releasing hormones. Such modulators are co-secreted messengers from hypothalamic sources or co-functioning at the pituitary cell level. Multichannel regulation of pituitary tropic hormones appears to be important for understanding the interactions of pharmacological agents with pituitary hormone release, on the one hand, and the modulation of hormone release in pathological conditions, on the other hand. Perinatal transient hazards may induce permanent alterations in adaptive behavior when tested in adult age. Corticosteroid-induced deviation of avoidance behavioral reactions may be opposed by simultaneous administration of ACTH-like peptides. These observations revealed that a balance of the glucocorticoids and ACTH-like peptides in perinatal period basically determine the adaptative reaction of animals in adult age. Immune system may be called as a mobile brain since its tremendous information capacity and its responsiveness to alterations of chemical environmental signals. Recent data support the view that there is a bidirectional communication between the neuro-endocrine adaptational axis and the immune system. Stress hormones can alter the immune response and mononuclear cells produce factors that change the neuroendocrine regulation. In addition to these, prohormones are synthesized in mononuclear cells that may be involved in regulation of signalization between cells and in activation of endocrine system and brain functions.

Animals↗

[Morphofunctional changes of the neurosecretory system and microcirculatory bed of the hypothalamus in patients with chronic alcoholic intoxication of varying degree].

Microcirculation was studied in the hypothalamus in acute alcohol intoxication. Blood flow was sharply decelerated with capillaries paretically dilated, overfilled with blood. Stasis, sludge formation and venue microthrombosis were directly related to the alcohol concentration in blood and urine. In neurosecretion areas the hemorrhagic sites were detected with neurosecretory cells activity sharply reduced. Chronical alcohol administration increased the number of functionally inactivated capillaries. These with luminal vesiculation were also found as were lymphoid cell infiltrates in venule walls. The number of capillaries inactivated in the neurosecretory system paralleled the number of dark cells that reflected the inhibition effects.

Adult↗

A histoenzymological investigation of the caudal neurosecretory system in six species of freshwater teleosts: a comparative study.

Enzymecytochemical features of the caudal neurosecretory system of 6 species of freshwater teleosts, Gudusia chapra, Gonialosa manmina (Clupeidae, Clupeiformes), Oxygaster bacaila (Cyprinidae, Cypriniformes), Mystus bleekeri (Bagridae, Cypriniformes), Sciaena coiter (Scienidae, Perciformes), and Mastacembelus pancalus (Mastacembelidae, Mastacembeliformes) have been investigated with the help of several specific histochemical techniques. No sex-dependent variation have been observed in the enzymecytochemical characteristics of the caudal neurosecretory system of the present species. The Dahlgren cells show intense RNA activity. Caudal neurosecretion lacks carbohydrate but seems to possess small amount of lipid. Acid-phosphatase is located in the Dahlgren cells and axons. Alkaline-phosphatase has been observed in the Dahlgren cells, axons, and urophysial blood-capillaries. Acetylcholine esterase is present in the Dahlgren cells, axons, and urophysis of Mystus, Mastacembelus, and Gonialosa, but lacking in the other 3 species. It is concluded that the caudal neurosecretory system of Mystus, Mastacembelus, and Gopialosa is innervated by cholinergic neurons. Despite their different taxonomic positions, caudal neurosecretory system of all 6 species produce similar responses to various enzymecytochemical tests, except for acetylcholine esterase.

Animals↗

Muscarine-stimulated neurotransmitter release from PC12 cells.

The effect of muscarine on neurosecretion was studied in the rat pheochromocytoma cell line, PC12. When PC12 cells were exposed to muscarine the cells responded rapidly with elevation of cellular inositol trisphosphate levels, elevation of intracellular free Ca++ and release of stored transmitter. These three phenomena were totally inhibited by the muscarinic antagonist, atropine, but were unaffected by the nicotinic antagonist, d-tubocurarine. Muscarine did not stimulate the production of cyclic GMP in these cells. The muscarine-stimulated increases in inositol trisphosphate, intracellular free Ca++ and neurotransmitter release displayed similar time courses and concentration dependencies suggesting that the secretion observed may be associated with the formation of inositol trisphosphate and elevation of intracellular free Ca++. The increase in intracellular free Ca++ appeared to be due to a mobilization of Ca++ from intracellular stores inasmuch as the increase in intracellular free Ca++ was not inhibited by the voltage-dependent Ca++ channel antagonist, nifedipine, at concentrations demonstrated to block K+-induced Ca++ influx into the cells, and little or no uptake of 45Ca++ was noted when cells were stimulated with muscarine. Elevation of inositol trisphosphate, intercellular free Ca++ and stimulation of transmitter release were, however, inhibited by the absence of extracellular Ca++. The results suggest that muscarine-stimulated release of neurotransmitter may be associated with an inositol trisphosphate-induced mobilization of intracellular Ca++.

Animals↗