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Biomedical subjects

M Palkovits

Publications and source records attributed to M Palkovits.

At least 145 records · Page 8Linked to original sources
PubMed1993

Stress-induced norepinephrine release in the paraventricular nucleus of rats with brainstem hemisections: a microdialysis study.

Immobilization (IMMO) of conscious rats evokes marked increases in release of norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus, consistent with a role of NE in the PVN release of corticotropin-releasing hormone and therefore in pituitary-adrenocortical activation during stress. The present study examined the effects of surgical hemisection of the brainstem between the locus ceruleus and rostral portion of the medulla on release of NE in the PVN of the hypothalamus in vivo in conscious rats, at baseline and during IMMO. Concentrations of NE, the intraneuronal NE metabolite dihydroxyphenylglycol (DHPG), and the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) were measured in microdialysate samples obtained beginning 24 h after implantation of a microdialysis probe in the PVN either ipsilateral or contralateral to the hemisection. On the lesioned side, baseline levels of NE, DHPG, and DOPAC were significantly lower and IMMO-induced increases were smaller than in sham-operated rats. Contralateral to the hemisection, DOPAC levels were significantly reduced. Neither baseline levels nor IMMO-induced increases in plasma corticosterone levels differed between lesioned and sham-operated animals. The present results indicate that: (1) NE release in the PVN at baseline and during IMMO depends mainly on ascending medullary tracts from ipsilateral brainstem A1 and A2 catecholaminergic areas, with small contributions from the locus ceruleus and from contralateral medullary cells, and (2) brainstem hemisection does not influence IMMO-induced activation of the hypothalamic-pituitary-adrenocortical axis as indicated by plasma corticosterone levels in conscious rats.

Animals↗
PubMed1993

Adrenalectomy augments in vivo release of norepinephrine in the paraventricular nucleus during immobilization stress.

Adrenalectomy (ADX) activates CRH neurons in the paraventricular nucleus (PVN) of the hypothalamus and increases hypothalamic norepinephrine (NE) turnover in vitro. Immobilization (IMMO) markedly increases the release of NE into extracellular fluid in the PVN. The present study assessed whether ADX affects the release of NE in the PVN in vivo in conscious rats at baseline and during IMMO and whether cortisol (CORT) treatment attenuates the effects of ADX. Concentrations of NE, the NE metabolites dihydroxyphenylglycol and methoxyhydroxyphenylglycol, and the dopamine metabolite dihydroxyphenylacetic acid were measured in microdialysate samples beginning 24 h after implantation of a microdialysis probe in the PVN. Seven to 10 days after ADX or ADX plus CORT (20 mg/kg.day via osmotic minipump), animals underwent IMMO for 2 h. Adrenalectomized rats had slightly higher baseline microdialysate NE, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid levels and much larger IMMO-induced responses of these compounds than did sham-operated rats. CORT treatment abolished the ADX-induced augmentation of these responses. The results indicate that ADX, by removing endogenous glucocorticoids, augments IMMO-induced release and turnover of NE and amplifies the responses of catecholamine synthesis. Glucocorticoids, therefore, appear to exert feedback inhibition on stress-induced increments in the release of NE and catecholamine biosynthesis in the PVN.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

A brain-tumor model utilizing stereotactic implantation of a permanent cannula.

A tumor model involving stereotactically implanted culture-reared tumor cells is presented. Stainless steel cannulas were stereotactically and permanently implanted into the caudate nucleus of 30 rats. The animals were separated into two groups. In Group I, 15 animals received a 10-microliters injection containing 10(6) C6 glioblastoma cells (five rats), 10(6) Walker 256 breast carcinoma cells (five rats), or cell medium (five rats). The coordinates were A(+1.5), L(+3.0), and DV(-5.0). In Group II, the coordinates were changed to A(+1.0), L(+3.0), and DV(-5.0) and the same number of rats received a 1-microliter injection containing 10(5) cells of each tumor in an attempt to produce more focal tumors. Two weeks after implantation, brain sections were stained with cresyl violet and a subset was stained for glial fibrillary acid protein (GFAP). A computerized morphometric analysis system was used to quantify tumor size. In Group I, the mean C6 tumor areas (+/- standard error of the mean) at specific coordinates were (in sq mm): A(+4.7) 0.4 +/- 0.2; A(+3.7) 3.5 +/- 1.1; A(+2.7) 5.7 +/- 1.7; A(+1.7) 9.5 +/- 2.3; A(+0.7) 7.5 +/- 3.2; A(-0.3) 3.7 +/- 2.9; and A(-1.3) 0.3 +/- 0.3. A nearly identical tumor mass and extension into the brain was produced in rats injected with Walker 256 cells. Similar C6 tumor areas were indicated in adjacent sections stained with cresyl violet and GFAP. Tumor was found in the caudate nucleus in all 10 rats, but not in the nucleus accumbens, fornix, or hippocampus. In Group II animals, tumor magnitude and extension into the brain were greatly reduced. The 10(6) cells in the 10-microliters volume was the most reliable tumor load for obtaining uniform tumors in different animals. The similarity of tumor distribution across different animals was indicated by the low variance of tumor area at specific anteroposterior coordinates. Reproducible and well-circumscribed caudate nucleus tumors were produced using this stereotactic procedure.

Animals↗
PubMed1992

Localization of targets for anti-ulcer drugs in cells of the immune system.

The gastric mucosa consists of the epithelium, which lines the lumen, the lamina propria, and the muscularis mucosae. The targets of drugs used to treat stomach and duodenal ulcers are thought to be the acid-secreting parietal cells of the epithelium. However, immune cells in the lamina propria are the only cells that showed detectable messenger RNAs for histamine, muscarinic, gastrin, and dopamine receptors by in situ hybridization histochemistry. None of the epithelial cells expressed any of these messenger RNAs. Thus, the targets of antiulcer drugs seem to be cells of the immune system in the gut and not parietal cells, as generally believed. This conclusion may revise the thinking about ulcer formation and may shed light on the etiology of such chronic small intestinal diseases as Crohn's disease.

Animals↗
PubMed1992

Regional distribution of glutamate and aspartate in adult and old human brain.

In previous studies on rat brain we found that the observed heterogeneity of the regional distribution of amino acids was much greater when small well-defined anatomical structures were assayed. We therefore reinvestigated the distribution of glutamate and aspartate in 50 discrete areas from adult and old human brain. The concentration of glutamate in the area of highest level was 4.5 and 4.7 times as high as in the area of lowest level in adult and old brain respectively; for aspartate these values were 3.0 and 6.6. Several changes in old brain were noted. The human pattern differed from that in rat.

Adult↗
PubMed1992

Noradrenergic activation in the paraventricular nucleus during acute and chronic immobilization stress in rats: an in vivo microdialysis study.

In vivo microdialysis was used to study the effects of single (2 h) or repeated (2 h for 7 consecutive days) immobilization (IMMO) stress on extracellular fluid concentrations of norepinephrine (NE) and the deaminated metabolites of NE and dopamine, dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) in the paraventricular nucleus of conscious rats. During IMMO, NE, DHPG, and DOPAC levels increased markedly, with similar peak values and time courses in the repeatedly stressed and previously unstressed groups. NE levels during a 2-h baseline period were lower in the repeatedly stressed group than in the unstressed group (99 +/- 9 pg/ml vs. 167 +/- 13 pg/ml, P less than 0.05), whereas DHPG (1,697 +/- 263 pg/ml vs. 1,424 +/- 194 pg/ml) and DOPAC (5,989 +/- 863 pg/ml vs. 4,428 +/- 1150 pg/ml) levels tended to be higher, so that the NE/DHPG ratio at baseline was significantly lower in the repeatedly stressed group (P less than 0.05). The results indicate that IMMO stress enhances NE release, reuptake, metabolism, and synthesis in the PVN. Repeated exposure to IMMO may decrease the microdialysate NE/DHPG ratio by inhibiting exocytotic release or enhancing neuronal reuptake of NE. In either case, the results suggest that repeated exposure to stress alters the release and disposition of NE in the PVN of conscious animals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Neuropeptides in the human superior cervical ganglion.

Superior cervical ganglia from 7 human cadavers (3-7 h post mortem) were immunostained for tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and 14 different neuropeptides. The results show that ganglionic cells contain TH, DBH, neuropeptide Y (NPY), somatostatin, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP). These substances were present predominantly within large ganglionic cells. Inside the ganglion, the number and topographical distribution of various types of immunoreactive cells differed from one another. NPY and CGRP immunoreactivities were found in some TH-positive cells, but that co-localization never exceeded the 30% of the TH cells. Leu-enkephalin showed a weak immunoreactivity, which was restricted to fibers or varicosities. Neuropeptides like substance P, dynorphin A and B, cholecystokinin, galanin, corticotropin-releasing factor, thyrotropin-releasing hormone, angiotensin II and neurotensin showed no immunoreactivity in the human superior cervical ganglion.

Calcitonin Gene-Related Peptide↗
PubMed1992

Peptidergic neurotransmitters in the endocrine hypothalamus.

More than 20 neuropeptides have been localized in the endocrine hypothalamus. They may exert a neurohormonal effect on the pituitary or innervate other neurons (intranuclear, intrahypothalamic or extrahypothalamic) and act as neurotransmitters. Many of the hypothalamic neuropeptides are synthesized as inactive precursors that are activated by proteolysis during axonal transport from the cell body to the synapse. Studies in which the paraventricular nuclei were bilaterally destroyed have shown that the neuroendocrine cells in the hypothalamus show functional plasticity and cells that do not usually make detectable quantities of a particular neuropeptide may be activated to do so. Within the hypothalamic nuclei are dense networks of synaptic connections among neurons synthesizing the same or different neuropeptides. These local circuits may coordinate the activities of peptidergic neurons in a hypothalamic nucleus. Hypothalamic neurons project axons to the median eminence-pituitary stalk and the posterior pituitary, also to nuclei within the hypothalamus and to extrahypothalamic areas such as the lower brainstem. Peptidergic neurons in the hypothalamus can have combined neurohormonal and neurotransmitter activities mediated by axon terminals on portal capillaries and other hypothalamic nuclei. Double labelling immunohistochemistry has been used to demonstrate reciprocal connections between peptidergic neurons in the hypothalamus, such as those synthesizing growth hormone-releasing hormone and somatostatin.

Animals↗
PubMed1992

Immunohistochemical study on the distribution of neuropeptides within the pontine tegmentum--particularly the parabrachial nuclei and the locus coeruleus of the human brain.

The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in human parabrachial nuclei and the pontine tegmentum with immunohistochemical stainings. Brains of seven adult human subjects of 35-72 years were fixed within 2 h post mortem. Serial sections were immunostained by antisera of 14 different neuropeptides--oxytocin, vasopressin, thyrotropin-releasing hormone, angiotensin II, calcitonin gene-related peptide, beta-endorphin, dynorphin A, dynorphin B, leucine-enkephalin, alpha-melanocyte stimulating hormone, substance P, neuropeptide Y, cholecystokinin and galanin--alternately. All of these peptides were found to be present in nerve fibers and terminals, but only two, angiotensin II and dynorphin B, in cell bodies of the parabrachial nuclei. Calcitonin gene-related peptide-, neuropeptide Y-, cholecystokinin- and galanin-immunoreactive cells were present in other areas of the pontine tegmentum, like the motor trigeminal nucleus, locus coeruleus, periventricular gray matter but not in the parabrachial nuclei. Peptidergic fibers were distributed unevenly throughout the pontine tegmentum having unique, individual distribution patterns. In the parabrachial nuclei, substance P, neuropeptide Y, cholecystokinin and galanin showed the highest density of immunoreactive neuronal networks. Moderate to low concentrations of immunoreactive processes were detected by calcitonin gene-related peptide, alpha-melanocyte stimulating hormone, dynorphin B, thyrotropin releasing hormone, leucine-enkephalin, dynorphin A, angiotensin II, beta-endorphin, vasopressin and oxytocin antisera, respectively. Other pontine tegmental areas, like the locus coeruleus, dorsal tegmental, pontine raphe and motor trigeminal nuclei as well as the central gray of the tegmental region exhibited a varying assortment of neuropeptides with distinct, individual localization patterns. Their detailed topographical distributions are mapped and given in coronal sections.

Adult↗
PubMed1992

Vascular ontogeny of the septal region in rats.

The development of the arterial and venous systems of the septum was studied in rat brains injected daily with India ink, from the 11th embryonic (E) until the first postnatal day. Arterial blood is supplied to the septum by the unpaired hemispheric artery, the stem and septal branches of which are to be recognized on the 14th and 15th embryonic days respectively. At earlier stages, e.g. on E12, a capillary network, the hemispheric plexus, can be seen between the two hemispheres contributing to the blood supply of the septum during the early phase (E14 to E18) of development. From E18 onwards, the arterial supply of the septum is derived only from direct branches of the hemispheric artery; one group of them being dorsal (infracallosal) and the other ventral (subcallosal). The venous drainage of the septum is bidirectional: 1) Veins of the ventral group leading to the interperioptic sinus are seen on E14. At first they collect blood only from a small rostral portion of the septum, but later their territory expands to include the anteroventral two-thirds of the septum. 2) The dorsal septal veins drain into the great cerebral vein (of Galen), or into the superior sagittal sinus directly. Initially, twigs run directly into the great cerebral vein. These later become the tributaries of the internal cerebral vein, which appears on E17 or E18. Until E18 this dorsally-directed drainage predominates, whereas at birth it becomes restricted to one third of the septum as a result of a gradual regression. The development of both arterial and venous circulations of the septum is complete at birth.

Animals↗
PubMed1992

The distribution of cathepsin D activity in adult and aging human brain regions.

We measured the activity of cathepsin D, the major cerebral protease, in 50 separate areas of the central nervous system of adult and aged humans, using hemoglobin as the substrate. The activity showed significant regional heterogeneity, with average differences of 50-100% between the lower and higher level areas, and a more than threefold difference between the lowest and highest levels. The forebrain, midbrain, and hindbrain each had areas of high and low activity; cerebellum and cord areas were among those with low activity. Cathepsin levels tended to increase with age in about half of the areas analyzed, and the increases were significant in 14. Statistically significant decreases with aging were observed in two areas. The increases varied between 30 and 60%, and the decreases were 20%. Enzyme activity in thalamus, hypothalamus, pons, medulla, and cerebellum increased with age. In the ventrolateral medulla, which contains the major portion of the cerebral noradrenergic cells, the cathepsin D levels increased with age; in the dorsal raphe area, which contains the major portion of the cerebral serotonergic cells, the enzyme levels decreased. The change with age in human brain seems to be less than what we observed in rat brain, where activity more than doubled in most areas. The changes in enzyme levels need to be tested at more ages to establish a pattern of changes in activity throughout life.

Adult↗
PubMed1992

Alterations in brain atrial natriuretic polypeptide levels in hypophysectomized rats.

Twelve days after hypophysectomy depleted atrial natriuretic polypeptide (ANP) concentrations were measured in the plasma and in 8 of 18 microdissected brain nuclei of rats. Reduced ANP levels were found in brain structures (subfornical organ, organum vasculosum laminae terminalis, preoptic and hypothalamic periventricular nuclei, paraventricular nucleus, lateral hypothalamic area), which are directly involved in the central regulations of salt and fluid homeostasis, as well as in the medial amygdaloid nucleus and the locus ceruleus. ANP concentrations in the median eminence, medial preoptic and arcuate nuclei did not alter by hypophysectomy. Elevated ANP concentrations were measured only in the supraoptic nucleus of hypophysectomized rats.

Amygdala↗
PubMed1992

Oxytocin nerve fibers innervate beta-endorphin neurons in the arcuate nucleus of the rat hypothalamus.

Fine, varicose oxytocin-containing nerve fibers have been demonstrated in the hypothalamic arcuate nucleus in rats. Using Phaseolus vulgaris leukoagglutinin as an anterograde tracer, fine neuronal fibers of paraventricular nucleus origin could be seen throughout the arcuate nucleus. Using double immunostaining, oxytocin-immunoreactive varicose fibers were observed around or in the close vicinity of beta-endorphin-immunoreactive neurons. Silver-gold-labeled oxytocin-immunoreactive presynaptic boutons were shown to make synaptic contacts with diaminobenzidine-labeled beta-endorphin-immunoreactive neurons by electron microscopy. These findings provide morphological evidence for a possible influence of oxytocin on the activity of the brain beta-endorphin system at the hypothalamic level.

Animals↗
PubMed1992

Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims.

Suicidal behavior has been associated with hypothalamic-pituitary-adrenal overactivity in humans, as measured by increased corticosteroid secretion. To investigate whether this overactivity is reflected at the pituitary level, we have studied the localization of pro-opiomelanocortin (POMC) mRNA, and glucocorticoid receptor (GR) mRNA, in human anterior pituitaries, and quantified these messages relative to controls. Pituitaries from 7 suicide victims and 11 cardiac deaths were sectioned into 10-microns slides, stained with thionin and processed for in situ hybridization using a riboprobe complementary to human POMC mRNA. To correct for possible postmortem cell loss, hybridization with P1B15, a cDNA complementary to rat cyclophillin mRNA, was used in adjacent sections. POMC mRNA containing cells were found to be localized in clusters and were highly associated with corticotropin-releasing hormone (CRH) receptors. In contrast, GR mRNA containing cells were distributed through the pituitary, although areas of increased density were associated with POMC mRNA cells. Quantification with a computerized image analysis system revealed a 25% increase in POMC message in suicide victims. Analysis of the corticotrophic cell clumps showed that the suicide victims had higher POMC mRNA density per cell (p = 0.04) and larger corticotrophic cell size (p = 0.04) than the cardiac death victims. No differences in GR mRNA were detected between the two groups, although GR and POMC mRNA levels were highly and significantly correlated (r = 0.8, p < 0.001). There were no differences in P1B15 message between the two groups. We conclude that in situ hybridization is a useful tool to study gene regulation in human neuroendocrine tissue and that suicide victims show evidence of chronic hypothalamic-pituitary-adrenal axis activation.

Adult↗