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M Palkovits

Publications and source records attributed to M Palkovits.

At least 181 records · Page 10Linked to original sources

Changes with aging in the levels of amino acids in rat CNS structural elements: III. Large neutral amino acids.

This paper reports the concentrations of valine, leucine, isoleucine, phenylalanine, and tyrosine as determined in 53 discrete brain areas of 3- and 29-month-old male Fischer 344 rats microdissected by the punch technique. The levels of other amino acids in the same areas are reported in other papers of this series. The essential amino acids reported in this paper showed great regional heterogeneity, with concentrations in areas of the highest content being 9 to 12 times higher than levels in areas of the lowest content. The relative distributions of these amino acids were fairly similar in that in a number of areas the amino acids were all at very high levels and in some other areas they were all at low levels, with a few exceptions. With aging, levels of some amino acids increased and levels of some others did not change, but the predominant change was a significant decrease in levels with age. The results indicate high regional heterogeneity in amino acid levels and in the changes of these levels with age.

Aging↗

Changes with aging in the levels of amino acids in rat CNS structural elements: IV. Methionine and basic amino acids.

This paper reports the distribution of methionine, histidine, lysine, arginine, and ornithine in 53 discrete brain areas of 3- and 29-month-old male Fischer 344 rats microdissected by the punch technique. Like that of the other amino acids were reported in previous papers of this series, the distribution of methionine and the basic amino acids was regionally highly heterogeneous. The ratios of levels in the areas of highest concentrations to levels in the areas of lowest concentration varied from 10 to 15 for these amino acids, except that it was 23 for arginine. This heterogeneity is also illustrated by the finding that in some areas arginine was more than 5% of the total amino acid content and in others was less than 0.5%. The distribution of methionine differed from that of the basic amino acids, which were high in hypothalamic areas and low in the limbic system. With aging, methionine and basic amino acids, like the other amino acids studied in this series, mainly decreased in level, although in a few cases increases could be seen. Significant decreases were noted more than five times as often as increases.

Aging↗

Autotransplantation of superior cervical ganglion to the caudate nucleus in three patients with Parkinson's disease (preliminary report).

Striatal cervical ganglionic implants have been utilized for the first time for treatment of three patients suffering from Parkinson's disease. Tissue grafts from the superior cervical ganglion have been dissected and immediately transplanted into the head of the caudate nucleus. The grafted tissue placed in a cavity of the caudate nucleus remains in contact with the cerebrospinal fluid in the lateral ventricle. Three and six months after surgery, none of the patients has had any major complications and their lower score of Unified Parkinsonism Rating Scale (UPRS) points was associated with an improvement of the signs of Parkinson's disease. Present data have provided some optimism that grafting of superior cervical ganglion is a feasible approach in Parkinson's disease.

Caudate Nucleus↗

Unique alterations of neuropeptide content in median eminence, amygdala, and dorsal vagal complex of 3- and 6-week-old diabetes mutant mice.

The nature of the genetic defects which define the obese (ob) and diabetes (db) loci in mice remain unknown, but both produce similar syndromes when maintained in the same strain of mice. There is some evidence suggesting a lesion in the central nervous system (CNS) in db/db mice, while ob/ob mice appear to have a primary lesion outside the CNS. In a search for further evidence of a unique central lesion in db/db mice, we have examined neuropeptide content in selected, microdissected brain areas in both of these mutants and lean controls. In order to rule out possible interactions of the db mutation with the genetic background, diabetes mice of both C57BL/KsJ and C57BL/6J strains were studied. When concentrations of nine neuropeptide immunoreactivities were examined in up to seven microdissected areas of the brain, C57BL/6J ob/ob mice showed only one reproducible alteration, a lower content of beta-endorphin-like immunoreactivity (LI) in the preoptic area at both 3 and 6 weeks of age as compared with lean littermates. In contrast, db/db mice of both C57BL/6J and C57BL/KsJ strains exhibited alterations in a total of four peptides in three brain areas: lower concentration of somatostatin-LI in median eminence, higher Met-enkephalin-LI in dorsal vagal complex of the medulla oblongata, higher substance P-LI and lower vasoactive intestinal polypeptide (VIP)-LI in amygdala. The concentrations of the peptides studied in medial basal hypothalamus, lateral hypothalamus, substantia nigra, and preoptic area were not reproducibly altered in db/db mice. These data provide preliminary evidence for unique brain abnormalities in db/db mice in specific areas that are involved in processing of neural signals that can affect the islets of Langerhans, gonadotrophin secretory patterns, and many other visceral functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗

The influences of hyperosmolality and synaptic inputs on galanin and vasopressin expression in the hypothalamus.

Galanin is a neuropeptide that is widely distributed throughout the rat central nervous system. It is co-localized with vasopressin in magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. Vasopressin biosynthesis is increased there by various hyperosmolar stimuli, including drinking 2% saline. We previously demonstrated that the chronically hyperosmolar Brattleboro rat has increased biosynthesis of galanin in the paraventricular and supraoptic nuclei. In this report we show using hybridization histochemistry that drinking 2% saline also increased galanin transcripts in these nuclei. We also demonstrate using hybridization histochemistry and immunohistochemistry that knife cuts that sever hypothalamo-hypophysial fibers transiently elevated galanin expression in the supraoptic nucleus ipsilateral to the lesion and depressed vasopressin expression ipsilaterally. Pituitary stalk transections also elevated galanin and decreased vasopressin transcripts. In addition, various knife cuts in the caudal hypothalamus were able to dissociate the expression of vasopressin and galanin, although co-localized and similarly affected by hyperosmolality in the supraoptic nucleus. Unilateral sagittal knife cuts that divided the posterior hypothalamus but avoided the hypothalamo-hypophysial pathway, as well as hemisections at the level of the premammillary area, resulted in ipsilateral elevations of galanin transcripts without significantly affecting vasopressin expression. These results indicate that independent intracellular signal transduction pathways exist for regulating expression of the two genes.

Animals↗

N-acetylaspartylglutamate: a transmitter candidate for the retinohypothalamic tract.

The retinohypothalamic tract is the neural pathway mediating the photic entrainment of circadian rhythms in mammals. Important targets for these retinal fibers are the suprachiasmatic nuclei (SCN) of the hypothalamus, which are thought to be primary sites for the biological clock. The neurotransmitters that operate in this projection system have not yet been determined. Immunohistochemistry and radioimmunoassay performed with affinity-purified antibodies to N-acetylaspartylglutamate (NAAG) demonstrate that this neuron-specific dipeptide, which may act as an excitatory neurotransmitter, is localized extensively in the retinohypothalamic tract and its target zones, including the SCN. Optic nerve transections resulted in significant reductions in NAAG immunoreactivity in the optic chiasm and SCN. Analysis of NAAG concentrations in micropunches of SCN, by means of radioimmunoassay, showed approximately 50% reductions in NAAG levels. These results suggest that this peptide may act as one of the neurotransmitters involved in retinohypothalamic communication and circadian rhythm entrainment.

Animals↗

Atrial natriuretic peptides in brain nuclei of rats with inherited diabetes insipidus (Brattleboro rats).

The concentration of atrial natriuretic peptides (ANF) was measured radioimmunologically in 18 selected microdissected brain areas of rats with inherited diabetes insipidus (Brattleboro rats) and their control rats (Long-Evans rats). In 7 brain areas known to be involved in the regulation of fluid homeostasis or blood pressure (subfornical organ, organum vasculosum lamina terminalis, periventricular preoptic nucleus, perifornical nucleus, nucleus of the solitary tract, tegmentum pontis, arcuate nucleus) ANF concentration was significantly changed. After restoration of antidiuresis with the V2 receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP) ANF levels of Brattleboro rats adapted at least partly to those of the control rats in all brain areas except the subfornical organ. Furthermore, ANF was then significantly changed in the supraoptic and paraventricular nuclei of DDAVP-treated diabetes insipidus rats. These data show that the central ANF system is sensitive for changes in electrolyte and fluid homeostasis.

Animals↗

Carboxypeptidase H in the hypothalamo-neurohypophysial system: evidence for processing and activation of a prohormone-processing enzyme during axonal transport.

Investigations of peptide precursor processing in nerve cells, including studies on prooxytocin and provasopressin processing in the rat hypothalamo-neurohypophysial system, show that prohormone processing occurs during axonal transport of maturing secretory vesicles. Recent studies (Fricker et al., 1989; Rodriguez et al., 1989) show that carboxypeptidase H (CPH), one of several proteases required for prohormone processing, is synthesized as a proenzyme that presumably requires activation. To determine if pro-CPH, like prohormone precursors, is processed and activated during axonal transport, we have analyzed the molecular forms of CPH present at several levels in the rat hypothalamo-neurohypophysial system. These biochemical and immunochemical studies showed that the supraoptic nucleus (SON), a region enriched in neuronal cell bodies, possesses primarily an inactive 65-kDa species of CPH. The median eminence and pituitary stalk regions that are enriched in axons possess both the inactive 65-kDa and the active 55-kDa forms of CPH, and nerve terminals of the posterior pituitary contain primarily the active 55-kDa CPH. These results support the hypothesis that pro-CPH is processed and activated during axonal transport from neuronal perikarya of SON to nerve terminals of the posterior pituitary. Furthermore, analysis of immunoreactive CPH in the rat and bovine pituitary showed that each tissue possessed different relative amounts of zymogen compared to mature forms of CPH, suggesting that tissue-specific processing of pro-CPH occurs. Thus, the biosynthesis of active peptide hormones requires the simultaneous processing of proenzyme and prohormone.

Animals↗

Effects of centrally administered substance P on cyclic AMP levels in particular brain areas of rats.

Effects of centrally (intracerebro-ventricularly) administered synthetic substance P on the metabolism of cAMP in 19 brain areas were investigated. Substance P administration increased cAMP levels considerably in the frontal cortex, the central gray matter and in the nucleus of the solitary tract, and to a lesser extent in the bed nucleus of the stria terminalis and in the anterior hypothalamic nucleus. Cyclic AMP levels were decreased in the globus pallidus, the habenula, the posterior hypothalamic nucleus and in the locus coeruleus while other brain areas showed no changes in cAMP levels.

Animals↗

Effect of atrial natriuretic peptide on the adenylate cyclase activity in the anterior and neurointermediate pituitary lobes of rats.

The effect of two atrial natriuretic peptides, rat ANP (3-28) and synthetic ANP (Arg101-Tyr126), on pituitary adenylate cyclase activity was measured in rats. Neither one was effective on basal, forskolin- or guanylylimidodiphosphate (GMP-PNP)-stimulated adenylate cyclase levels measured in homogenates of anterior and neurointermediate pituitary lobes. High concentrations (10(-7) and 10(-6) M) of ANPs further stimulate NaF-induced high adenylate cyclase activity - ANP (3-28) in both lobes, ANP (Arg101-Tyr126) only in the anterior lobe-but they were without effect in 10(-8) M or lower concentrations. These data indicate that ANP may not influence adenylate cyclase/cAMP system in the rat pituitary gland.

Adenylyl Cyclases↗

Atrial natriuretic factor in central nervous system regulatory mechanisms: effect of experimental alterations in water and salt homeostasis and blood pressure.

Concentrations of atrial natriuretic factor (ANF) were measured in discrete brain nuclei by radioimmunoassay in rats. Alterations in the salt and fluid homeostasis and aldosterone treatment resulted in marked changes of ANF levels in the preoptic-hypothalamic periventricular structures including the organum vasculosum laminae terminalis, in the subfornical organ and the perifornical nucleus. Furthermore, marked changes were observed in ANF levels of these nuclei in various types of renal hypertensions. Altered ANF levels were found in several brain nuclei (locus coeruleus, dorsal raphe nucleus, tegmentum pontis, nucleus of the solitary tract) of animals with diabetes insipidus or spontaneous hypertension.

Animals↗

Atrial natriuretic factor in central nervous system regulatory mechanisms: effect of experimental alterations in water and salt homeostasis and blood pressure.

Atrial natriuretic factor (ANF) is widely distributed in the preoptic area and the hypothalamus, it is present there both in cell bodies and nerve terminals. Effect of experimental alterations in the salt and water balance was examined on preoptic-hypothalamic ANF levels measured in ten microdissected nuclei. Immunohistochemical analysis was also performed to confirm radioimmunological results. Following interventions were performed in adult male rats: adrenalectomy (5 days), daily 0.9% NaCl, aldosterone (5 micrograms/100 g) and dexamethasone (2 micrograms/ml drinking water) treatments in both intact and adrenalectomized groups, and in rats with diabetes insipidus (Brattleboro rats) and DOC-salt hypertension. Although no appreciable alterations were observed in the intensity of ANF-like immunoreactivity in sections of the preoptic-hypothalamic region, ANF levels altered markedly in the periventricular structures (organum vasculosum laminae terminalis, preoptic and periventricular nuclei). Little or no changes were measured in ANF levels of other hypothalamic nuclei (except the perifornical nucleus). Adrenalectomy depleted ANF levels which were restored by NaCl drinking. Aldosterone elevated ANF concentrations both in intact and adrenalectomized animals while dexamethasone treatment was without any significant effect on ANF levels in the periventricular preoptic nucleus. Diabetes insipidus or DOC-salt hypertension had little or no effect on ANF levels in this brain area. Unchanged ANF concentrations were also measured in the vasopressin-containing supraoptic nucleus following adrenalectomy or in diabetes insipidus rats.

Animals↗

Collateral sprouting of somatostatin-immunoreactive axons after partial deafferentation of the central nucleus of the rat amygdala.

These experiments utilize a paradigm developed to study plastic responses of peptidergic neurons in a discrete brain area following deafferentation. The central nucleus of the amygdala (CNA) is richly innervated by somatostatin-immunoreactive (SS-I) terminal axons. In the course of preliminary light microscopic (LM) investigations by this laboratory, changes were observed in the density of presumed SS-I terminals in the rat CNA after lesioning the medial input. The LM finding of increased density of presumed SS-I terminals in the CNA at the 10-day post-lesion stage underscored the need for a quantitative electron microscopic (EM) study of the SS-I components, including an evaluation of synaptic events at different survival periods. At the 3-day post-lesion stage, EM examination showed degenerating axons in the lesioned CNA, many already engulfed by astrocytes. None of the degenerating profiles were SS-I, supporting the view that the lesion did not interrupt, to any significant extent, SS-I axons entering the nucleus. EM surveys of the 10-day post-lesion material demonstrated that degenerated profiles had almost completely disappeared. Numbers of SS-I axon terminals, particularly of smaller-sized profiles, were increased by 22% over control value. Synaptic frequency was decreased by 16% below control value. Numbers of SS-I terminals making synapses were increased 3.4% above control value. At the 30-day post-lesion stage, the total number of SS-I terminal axons had increased 86% over controls, whereas the synaptic frequency had decreased by about a third below controls. The absolute number of SS-I terminals engaging in synapses had increased by 24% over controls. The 90-day post-lesion CNA showed a further increase in the number of SS-I axon profiles: 136% over control value. The synapse-to-axon ratio (synaptic frequency) of 27% was similar to that observed for the CNA from the unlesioned side or from unoperated animals. At this stage the number of SS-I synapses had increased by 135% over controls. This model presents many possibilities for studying neuroplasticity, particularly involving peptidergic neurons of the central autonomic nervous system.

Amygdala↗

Substance P-like immunoreactive neurons in the arcuate nucleus project to the median eminence in rat.

Substance P-containing nerve fibers in the median eminence of rat arise in cells located in the arcuate nucleus. Two days following surgical lesioning of the median eminence immunoreactive substance P accumulated in neuronal perikarya in the middle part (rostrocaudally) of the arcuate nucleus, mainly in its ventromedial portion. Substance P-immunostained cells appeared nowhere else in the hypothalamus following surgical lesion of the median eminence while they were found in several hypothalamic and extrahypothalamic cell groups after colchicine treatment.

Animals↗

Electron microscopic immunocytochemical evidence for the existence of bidirectional synaptic connections between growth hormone-releasing hormone- and somatostatin-containing neurons in the hypothalamus of the rat.

Synaptic contacts between growth hormone-releasing hormone (GHRH)- and somatostatin-containing neurons were demonstrated in the rat hypothalamus by a double-staining immunocytochemical method at the electron microscopic level. Somatostatin-immunoreactive nerve terminals synapse on GHRH-positive dendrites and cell bodies in the arcuate nucleus. A fine network of GHRH-immunopositive nerve terminals was observed at the light microscopic level in the rostral part of the periventricular nucleus and in the dorsal part of the arcuate nucleus around somatostatin-containing neuronal elements. With the electron microscope synaptic contact between GHRH-containing nerve terminals and somatostatin-containing dendrites are demonstrated. The reciprocal innervation between GHRH- and somatostatin-containing neurons that project to the median eminence and regulate growth hormone secretion must allow them to coordinate their activities.

Animals↗

Changes with aging in the levels of amino acids in rat CNS structural elements. I. Glutamate and related amino acids.

Glutamate and related amino acids were determined in 53 discrete brain areas of 3- and 29-month-old male Fischer 344 rats microdissected with the punch technique. The levels of amino acids showed high regional variation - the ratio of the highest to lowest level was 9 for aspartate, 5 for glutamate, 6 for glutamine, and 21 for GABA. Several areas were found to have all four amino acids at very high or at very low level, but also some areas had some amino acids at high, others at low level. With age, in more than half of the areas, significant changes could be observed; decrease occurred 5 times more frequently than increase. Changes occurred more often in levels of aspartate and GABA than in those of glutamate or glutamine. The regional levels of glutamate and its related amino acids show severalfold variations, with the levels tending to decrease in the aged brain.

Aging↗

Changes with aging in the levels of amino acids in rat CNS structural elements. II. Taurine and small neutral amino acids.

Taurine (Tau) and the small neutral amino acids glycine (Gly), serine (Ser), threonine (Thr), and alanine (Ala) were measured in 53 brain areas of 3- and 29-month-old male Fisher 344 rats. The ratio of highest to lowest level was 34 for Tau, 9.1 for Thr, 7.6 for Gly and Ser, and 6.5 for Ala. The heterogeneity was found in numerous areas; for example, Tau levels were more than 90 nmol/mg protein in 6 areas, and less than 20 nmol/mg protein in 10 areas. Similar heterogeneity was found with the other amino acids. The relative distribution of the small neutral amino acids showed several similarities; Tau distribution was different. With age, four amino acids decreased in 10-18 areas, and increased in only 1-3, while Thr increased in more areas than it decreased. The five amino acids of this paper, and the four of the previous paper, are among the amino acids at highest level in the brain; the sequence in their levels shows considerable regional heterogeneity.

Aging↗