Impact of a galanin antagonist on exogenous galanin and natural patterns of fat ingestion.

The peptide galanin (GAL) has a potent stimulatory effect on fat ingestion after administration into the hypothalamic paraventricular nucleus (PVN). This study examined a newly synthesized GAL antagonist, M40, in two separate experiments involving: (1) PVN injections of M40 alone in freely feeding animals, to investigate the importance of endogenous GAL receptor activity in determining natural patterns of fat ingestion, and (2) PVN injections of M40 in combination with exogenous GAL, to determine whether endogenous GAL receptors mediate this peptide-induced response. The results demonstrate that PVN injection of M40 by itself dose-dependently (2-108 pmol) reduces spontaneous ingestion of the fat diet.

Effects of adrenal steroid agonists on food intake and macronutrient selection.

These experiments tested the effects of subcutaneous (SC) and paraventricular nucleus (PVN) administration of the steroid receptor agonists, corticosterone (CORT), aldosterone (ALDO), RU28362, and dexamethasone (DEX), on food intake and macronutrient selection during the first h of the dark feeding period in the rat. Results indicate that CORT and the selective type II receptor agonist RU28362 specifically stimulate carbohydrate ingestion after SC or PVN administration, while DEX has no effect on feeding. This selective effect of SC CORT on carbohydrate ingestion is dose dependent, seen at doses ranging from 0.

Neurochemical-neuroendocrine systems in the brain controlling macronutrient intake and metabolism.

Appetite, energy balance and body weight gain are modulated by diverse neurochemical and neuroendocrine signals from different organs in the body and diverse regions in the brain. The hypothalamus plays an important integrative function in this process, acting through a variety of systems that involve a close interaction between nutrients, amines, neuropeptides and hormones. These systems underlie normal nutrient intake and metabolism and are thought to be responsible for shifts in feeding behavior across the circadian cycle and fluctuations relating to gender and age in both rats and humans.

The pharmaco-ontogeny of the perifornical lateral hypothalamic beta 2-adrenergic and dopaminergic receptor systems mediating epinephrine- and dopamine-induced suppression of feeding in the rat.

The functional ontogeny of beta 2-adrenergic and dopaminergic receptors in the perifornical lateral hypothalamus (PLH) that mediate adrenergic and dopaminergic suppression of feeding in rats was investigated. Rat pups, ranging in age from 2 to 15 days, were removed from their mothers and implanted with a brain cannula directed unilaterally at the PLH or a more rostral site lateral to the anterior nucleus of the hypothalamus. On the next day, following a 22-h period of food and water deprivation, each pup was implanted with an intra-oral cannula for oral infusion of milk that could be swallowed or rejected.

Blockade of natural and neuropeptide Y-induced carbohydrate feeding by a receptor antagonist PYX-2.

Neuropeptide Y (NPY injected into the paraventricular nucleus (PVN) of rats has a potent stimulatory effect specifically on carbohydrate intake. This study examined the behavioral effects of a newly synthesized NPY antagonist, PYX-2. After PVN injection of PYX-2 (50-900 pmoles) alone, a strong dose-dependent reduction in spontaneous carbohydrate intake at the onset of the dark cycle was observed in freely-feeding rats.

Effect of food deprivation and refeeding on the concentration of vasopressin and oxytocin in discrete hypothalamic sites.

Recent evidence has implicated hypothalamic peptides, such as arginine vasopressin (AVP) and oxytocin (OT) in the control of feeding behavior. In this study, we investigated the impact of food deprivation (48 h) and subsequent refeeding (6 h) on the concentration of AVP and OT in discrete hypothalamic areas, as well as in the neurohypophysis. We also estimated in these rats certain peripheral measures, including hydroelectrolytic parameters, plasma and urine AVP, and plasma corticosterone.

The pharmaco-ontogeny of the paraventricular alpha 2-noradrenergic receptor system mediating norepinephrine-induced feeding in the rat.

The present study was undertaken to assess the functional ontogeny of alpha 2-noradrenergic receptors in the hypothalamic paraventricular nucleus (PVN) that mediate noradrenergic stimulation of feeding in the rat. Rat pups, ranging in age from 2 to 15 days, were removed from their mothers and implanted with a brain cannula directed unilaterally at the PVN or third ventricle. On the following day, each pup was implanted with an intra-oral cannula for oral infusion of milk or water that could be swallowed or rejected.

Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y1 receptor mediating this peptide's effect.

Neuropeptide Y (NPY) elicits eating when injected directly into the paraventricular nucleus (PVN) or perifornical hypothalamus (PFH). To identify the essential regions of the NPY molecule and the relative contributions of Y1 and Y2 receptors, the eating stimulatory potency of NPY was compared to that of its fragments, analogues, and agonists when injected into the PVN or PFH of satiated rats. Additionally, antisera to NPY was injected into the cerebral ventricles (ICV) to determine whether passive immunization suppresses the eating produced by mild food deprivation.

Sural nerve biopsies in Guillain-Barre syndrome: axonal degeneration and macrophage-associated demyelination and absence of cytomegalovirus genome.

T-cell infiltration was detected by immunohistochemistry in only 2 of 10 sural nerve biopsies from patients with Guillain-Barré syndrome (GBS). The number of endoneurial macrophages, identified by the monoclonal antibody MAC 387, was increased, compared with the number in 10 cases of axonal neuropathy. Macrophage-associated demyelination was identified in 7 and axonal degeneration in 8 cases.

Metabolic effects of galanin injections into the paraventricular nucleus of the hypothalamus.

The metabolic effects of single injections of galanin into the paraventricular nucleus of the hypothalamus (PVN) were investigated in an open-circuit calorimeter. Wistar rats were tested, with no food available during the tests. In the dose range of 0.

Differential effects of galanin and neuropeptide Y on extracellular norepinephrine levels in the paraventricular hypothalamic nucleus of the rat: a microdialysis study.

Evidence suggests that the peptides galanin (GAL) and neuropeptide Y (NPY) interact with the amine norepinephrine (NE) in the hypothalamic paraventricular nucleus (PVN) to stimulate feeding behavior. To directly investigate the nature of these interactions, extracellular levels of PVN NE were monitored in freely-moving rats using the microdialysis/HPLC technique. Following PVN administration of GAL (0.

Effects of adrenalectomy on macronutrient selection patterns in the rat.

The present studies examined the effects of adrenalectomy (ADX) on nutrient selection of rats over the 24-h period, as well as during the first 2 h of the nocturnal feeding cycle. Results indicate that ADX, in rats showing generally similar preferences for carbohydrate and fat, equally suppresses intake of both of these nutrients over the 24-h period. The relative impact of ADX on carbohydrate and fat intake may shift depending upon baseline, with carbohydrate-preferring rats showing a stronger decrease in intake of this diet after ADX and fat-preferring rats exhibiting a greater decline in fat intake after ADX.

Self-selecting albino rats exhibit differential preferences for pure macronutrient diets: characterization of three subpopulations.

Analyses of natural feeding behavior in albino male Sprague-Dawley rats demonstrate that, when allowed to self-select from pure macronutrient diets (protein, carbohydrate and fat), these rats of the same genetic strain can be categorized into 3 subpopulations according to either their 24-h or their 12-h nocturnal patterns of nutrient intake. A majority of the animals (HC for high carbohydrate, 50% of the total population) consumed a diet rich in carbohydrate relative to protein or fat, while a smaller population of rats (HF, 30%) preferred the fat diet, and an even smaller population (HP, 20%) chose a high-protein diet. These 3 subpopulations, after a few weeks of maintenance on the diets, differed in their body weight, with the HF rats having a higher body weight than the HP animals, who tended to weigh more than the lightest HC rats.

Developmental patterns of macronutrient intake in female and male rats from weaning to maturity.

Male and female Sprague-Dawley rats had available pure macronutrient diets, protein, carbohydrate and fat, from birth to day 77 of age. Analyses of their intake of these nutrients, as a function of age, demonstrate that, in both sexes, daily protein intake and preference for this nutrient relative to the other macronutrients rise steadily from weaning and peak precisely at the time of puberty (day 37-44 for females and days 42-49 for males), when there is also a peak in body weight gain. This is in contrast to daily carbohydrate intake, which peaks 2 weeks after puberty in males, and also to the female and male rats' preference for carbohydrate, which remains relatively stable from weaning to maturity.

Higher alpha-noradrenergic receptors in paraventricular nucleus of obese Zucker rats: decline after food deprivation.

Norepinephrine (NE), acting through alpha 2-noradrenergic receptors in the hypothalamic paraventricular nucleus (PVN), has been implicated in the control of feeding behavior and body weight gain. To determine whether this hypothalamic receptor system is disturbed in genetically obese rats, the binding of radioligands to alpha 2-noradrenergic, as well as to alpha 1-noradrenergic, receptors was examined in seven hypothalamic nuclei of obese Zucker rats relative to their lean littermates. Receptor binding procedures, using the alpha 2-noradrenergic agonist [3H]p-aminoclonidine ([3H]PAC) and the alpha 1-noradrenergic antagonist [3H]prazosin, demonstrated that the obese rats, compared to the lean rats, had significantly greater alpha 2-noradrenergic and alpha 1-noradrenergic receptor binding, specifically in the PVN as opposed to other hypothalamic areas examined.

Analysis of neuropeptide Y-induced feeding: dissociation of Y1 and Y2 receptor effects on natural meal patterns.

To differentiate NPY receptor subtypes, Y1 and Y2, in terms of their impact on feeding behavior, the intact molecule NPY(1-36) and the 3 fragments, NPY(2-36), the Y1 agonist [Leu31,Pro34]NPY, and the Y2 agonist NPY(13-36), were injected (100 pmol/0.3 microliters) into the hypothalamic paraventricular nucleus (PVN) of freely feeding rats. A computer-automated data acquisition system was employed in these experiments to permit a detailed analysis of feeding over the 12-h nocturnal cycle, in animals maintained on pure macronutrient diets.

The clinical spectrum of peripheral neuropathies associated with benign monoclonal IgM, IgG and IgA paraproteinaemia. Comparative clinical, immunological and nerve biopsy findings.

Observations have been made on a consecutive series of 62 patients with peripheral neuropathy associated with benign monoclonal paraproteinaemia. The paraprotein class was IgM in 46 cases, IgG in 11 and IgA in 5. Although showing variations between patients, the clinical picture was similar for those with either IgM or IgG paraproteins, usually consisting of a late-onset, slowly progressive, distal sensorimotor demyelinating polyneuropathy, often with tremor and ataxia as prominent features.

Brain neuropeptide Y: an integrator of endocrine, metabolic and behavioral processes.

Neuropeptide Y (NPY), acting through various medial hypothalamic nuclei, is found to have potent effects on a variety of endocrine, physiological and behavioral systems that modulate energy balance. This peptide affects the release of various hormones, such as corticosterone, insulin, aldosterone and vasopressin, which modulate energy metabolism, as well as food intake. It also has direct impact on energy metabolism through an effect on substrate utilization and lipogenesis.

A clinicopathological study of the Guillain-Barré syndrome. Nine cases and literature review.

The postmortem findings are reported from 9 cases of the Guillain-Barré syndrome with survival between 10 days and 1 yr. In 8 cases there was multifocal loss of myelin throughout the peripheral nervous system with relative preservation of axons. In 1 case there was predominant loss of axons.

Sarcoid neuropathy.

In a case of subacute sensory and motor polyneuropathy associated with sarcoidosis, multiple epineurial and endoneurial granulomas were demonstrated in a sural nerve. Neighbouring nerve fibres were displaced by the granulomas and some were undergoing axonal degeneration. Ultrastructural and teased fibre studies showed axonal atrophy and degeneration with secondary demyelination.

Effect of hypothalamic and peripheral fluoxetine injection on natural patterns of macronutrient intake in the rat.

The effect of the serotonin (5-HT) reuptake inhibitor, fluoxetine (FLU), on nutrient intake was examined in rats given free access to three pure macronutrient diets (protein, carbohydrate and fat). Fluoxetine was administered either peripherally or directly into the hypothalamic paraventricular nucleus (PVN) at three different times of the rats' nocturnal cycle. Using a range of doses for IP (0.

Diurnal rhythm of neuropeptide Y-like immunoreactivity in the suprachiasmatic, arcuate and paraventricular nuclei and other hypothalamic sites.

The diurnal rhythm of neuropeptide Y (NPY)-like immunoreactivity was examined in 9 discrete hypothalamic sites of rats maintained on a 12:12 h light/dark cycle. Significant bimodal rhythms of NPY concentration were detected in the suprachiasmatic and arcuate nuclei, with significant peaks just prior to onset of the nocturnal period and also at onset of the light period. In the parvocellular division of the paraventricular nucleus, a unimodal NPY peak was observed prior to dark onset.

Galanin inhibits insulin and corticosterone release after injection into the PVN.

The neuropeptide galanin (GAL, 1 microgram/0.3 microliters) was injected into the paraventricular nucleus (PVN) at two different times of the 12:12 h light/dark cycle, namely 2 h before the dark ('pre-dark') and before the light ('pre-light') periods. Blood samples were collected 15 min after injection and examined for serum levels of insulin (INS), corticosterone (CORT) and glucose (GLUC).

Impact of hypothalamic d-norfenfluramine and peripheral d-fenfluramine injection on macronutrient intake in the rat.

Previous research with hypothalamic injection of serotonin (5-HT) has suggested that this monoamine may act within the medial hypothalamus to suppress carbohydrate intake in a selective, phasic and circadian-related fashion. To explore further the action of 5-HT in the brain, the present studies tested the serotonergic stimulants, d-norfenfluramine (DNF) and d-fenfluramine (DF), in freely feeding, brain-cannulated animals maintained on pure macronutrient diets (protein, carbohydrate and fat) and tested at different times of the diurnal cycle. The results show that administration of DNF into the paraventricular nucleus (PVN) potently influences appetite for a specific nutrient at a particular time of the light-dark cycle.