Biomedical subjects

U Pesonen

Publications and source records attributed to U Pesonen.

46 records · Page 3Linked to original sources

PubMed1992

Hypothalamic neuropeptide expression after food restriction in Zucker rats: evidence of persistent neuropeptide Y gene activation.

The Obese Zucker rat is a model of genetic obesity characterized by hyperphagia, hyperinsulinemia and other endocrine abnormalities. In order to elucidate pathogenetic mechanisms contributing to disturbed feeding behavior in these animals, the effect of food restriction on three hypothalamic neuropeptides involved in the control of food intake was studied. Eighteen male obese and 18 lean Zucker rats were randomly divided into two groups: half of the animals were food-restricted for 2 weeks, while the other half served as controls and were fed ad libitum. The levels of preproneuropeptide Y (preproNPY), preprocorticotropin releasing factor (preproCRF) and preprosomatostatin (preproSOM) mRNAs were determined using in situ hybridization technique. In addition, plasma insulin and corticosterone concentrations were analyzed. Food restriction significantly increased the expression of preproNPY mRNA in the arcuate nucleus in both Zucker phenotypes, while the expressions of preproCRF mRNA in the paraventricular nucleus (PVN) and preproSOM mRNA in the periventricular nucleus (PeV) were not altered. The expression of preproNPY mRNA was significantly greater in control obese animals compared to control lean animals. Food restriction lowered plasma insulin levels, but did not change plasma corticosterone levels. It is concluded that food restriction specifically activates NPY gene transcription in the arcuate nucleus the response being similar in both Zucker phenotypes. The results suggest that orexigenic NPY plays a role in the adaptation to altered feeding status.

Animals↗

PubMed1992

Differential hypothalamic arginine vasopressin response to glucocorticoid receptor antagonism in lean and obese Zucker rats.

The obese Zucker rat (fa/fa) is an animal model for genetic obesity characterized by hyperphagia, hyperinsulinemia, and severe insulin resistance in peripheral tissues. Adrenal steroids seem to play an important role in the onset of fatty syndrome in these animals. There is strong evidence of abnormal regulation of the hypothalamic-pituitary-adrenal axis in obese Zucker rats. Considering the physiological function of arginine vasopressin (AVP) as an adrenocorticotropic hormone secretagogue, the present study was carried out to investigate the role of glucocorticoids in the control of hypothalamic AVP systems in lean and obese Zucker rats. In the first experiment, mifepristone (RU 38486), a glucocorticoid receptor antagonist, was administered for 4 days (10 mg/kg orally twice daily), and the expression of AVP mRNA in hypothalamic paraventricular and supraoptic nuclei was measured using in situ hybridization, and the concentrations of AVP in the pituitary gland and in the median eminence were quantified. Plasma corticosterone levels were also analyzed. Mifepristone treatment resulted in a threefold increase in plasma corticosterone levels in lean Zucker rats, but it did not change corticosterone secretion in obese animals. Mifepristone treatment decreased AVP mRNA levels in lean animals in the supraoptic nuclei, while in obese animals the AVP mRNA content was increased in the paraventricular nuclei. Mifepristone treatment significantly increased the concentration of AVP in the median eminence in lean rats and decreased it in obese animals. Mifepristone treatment did not change concentrations of AVP in the pituitary gland. In the second experiment, mifepristone was given for 4 days (10 mg/kg orally twice daily), and its effects on 24-hour food intake and plasma AVP concentrations were measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The glucocorticoid antagonist mifepristone reveals abnormal regulation of the adrenocortical system in obese Zucker rats.

The effects of the potent glucocorticoid type-II receptor (GR) antagonist, mifepristone, on corticosterone secretion and on expression of preprocorticotrophin-releasing factor (preproCRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and of pro-opiomelanocortin (POMC) mRNA in the pituitary gland were investigated in lean and obese Zucker rats. Treatment with mifepristone for 4 days (10 mg/kg orally twice daily) significantly (P less than 0.05) stimulated corticosterone secretion in lean but not in obese rats. In lean rats the enhanced corticosterone secretion was associated with non-significant increments in the expression of preproCRF mRNA in the PVN and of POMC mRNA in the pituitary gland, while mifepristone significantly (P less than 0.05) reduced the expression of preproCRF mRNA in the PVN of obese Zucker rats. It is concluded that antagonism of GR by mifepristone results in persistent activation of the adrenocortical axis in lean Zucker rats due to blockade of feedback inhibition by circulating corticosterone. In obese animals the abnormal response to mifepristone suggests that the neuroendocrine control of the HPA axis is altered in genetically determined obesity.

Animals↗

PubMed1991

Brain monoamine metabolism and rotational behaviour induced by experimental herpes simplex virus encephalitis.

The motor behaviour and brain concentrations of dopamine, noradrenaline, serotonin and their metabolites have been examined in rabbits with experimental herpes simplex virus (HSV) brain infection achieved by unilateral corneal inoculation. The animals showed altered motor behaviour, consisting of a posture tilting to the side of inoculation and circling in the same direction, that began on day 4-5 post inoculation, and was most vigorous on day 7 post inoculation. Compared with controls, the concentration of 5-hydroxyindoleacetic acid was increased in the caudate nucleus on both sides and that of serotonin was decreased in the nucleus accumbens on the side of inoculation. The circling of the animals correlated positively with the ratio of homovanillic acid concentrations between the left and right caudate nucleus, although the actual concentrations did not differ from the controls. The posture asymmetry correlated with the ratio of the left and right nucleus accumbens homovanillic acid concentrations. The results demonstrate that experimental HSV infection in the brain alters motor behaviour, in association with changes in brain dopamine and serotonin metabolism in the major ascending monoamine systems.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Effects of repeated administration of mifepristone and 8-OH-DPAT on expression of preproneuropeptide Y mRNA in the arcuate nucleus of obese Zucker rats.

Neuropeptide Y (NPY) is an important hypothalamic regulator of feeding behavior. In this study we have investigated the regulation of the expression of preproNPY mRNA in male obese and lean Zucker rats by in situ hybridization. These animals represent a model of genetic obesity with hyperphagia, hyperinsulinemia and altered endocrine functions. Obese Zucker rats, treated for 12 days with 0.9% saline, had about 210% higher level of basal preproNPY mRNA expression in the arcuate nucleus when compared to their lean littermate controls. Repeated administrations of 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), a serotonergic 5-HT1A agonist, or mifepristone, a glucocorticoid receptor antagonist, did not modify the basal expression of preproNPY mRNA in the Zucker phenotypes. The 8-OH-DPAT treatment significantly reduced hyperinsulinemia in obese Zucker rats without changing plasma glucose levels. The mifepristone treatment significantly increased plasma corticosterone levels in lean animals, but not in obese animals. The present study demonstrates enhanced expression of preproNPY mRNA in the arcuate nucleus in obese Zucker rats suggesting an involvement of NPY in the pathophysiology of the hyperphagic syndrome and genetically determined obesity in Zucker rats. Neither the antagonism of glucocorticoid receptors by mifepristone, nor repeated treatment with 8-OH-DPAT resulting in reduced insulin levels in obese Zucker rats, modified the basal expression of preproNPY mRNA in the arcuate nucleus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1990

Chronic dexmedetomidine, a selective alpha 2-agonist, decreases serotonin but not noradrenaline turnover in rat brainstem nuclei.

The effects of a chronic treatment with dexmedetomidine, the active d-isomer of a selective alpha 2-agonist, medetomidine, on the metabolism and turnover of catecholamines and indoleamines in discrete rat brain stem and mesencephalic nuclei were investigated. Chronic dexmedetomidine (3 or 10 micrograms/kg per h for 14 days, delivered by osmotic minipumps) did not change the basal concentrations of noradrenaline, dopamine or 3,4-dihydroxyphenylacetic acid, or the rates of accumulation of 3,4-dihydroxyphenylalanine after inhibition of decarboxylase by NSD 1015. In contrast, the concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and/or 5-HIAA/5-HT were significantly reduced in the nucleus tractus solitarii, raphe dorsalis, locus coeruleus, A1-C1 area, A9 and A10 areas after 10 micrograms/kg per h of dexmedetomidine. The accumulation of 5-hydroxytryptophan was significantly reduced in the locus coeruleus and nucleus tractus solitarii. It is concluded that chronic dexmedetomidine treatment significantly decreases the turnover of 5-hydroxytryptamine in discrete brainstem and mesencephalic nuclei, while the rate of synthesis of noradrenaline in the same areas is not changed.

Adrenergic alpha-Agonists↗

PubMed1990

Hypothalamic 5-hydroxytryptamine metabolism is not influenced by streptozotocin-diabetes induced at neonatal age.

Rats were rendered diabetic at neonatal age by an intraperitoneal injection of streptozotocin (90 mg/kg). At 8-10 weeks of age, their 5-HT and 5-HIAA levels in different hypothalamic nuclei (ventromedial, paraventricular, periventricular, supraoptical and suprachiasmatic nuclei) were similar to control animals which received vehicle only. It is concluded that the combination of mild hyperglycemia and hypoinsulinemia does not affect hypothalamic 5-HT metabolism in rats.

Animals↗

PubMed1990

Hypothalamic neurochemistry and feeding behavioral responses to clonidine, an alpha-2-agonist, and to trifluoromethylphenylpiperazine, a putative 5-hydroxytryptamine-1B agonist, in genetically obese Zucker rats.

Genetically obese Zucker rats are hyperphagic, hyperinsulinemic and hyperlipemic. In order to investigate pathophysiological mechanisms underlying hyperphagia in these animals, monoamine metabolism and turnover were studied in discrete hypothalamic nuclei known to participate in the control of feeding behavior. Neurochemical studies in genetically obese Zucker rats and in their lean littermate controls were complemented by investigating feeding behavioral responses to the acute administration of clonidine (15 and 30 micrograms/kg i.p.), an alpha 2-adrenoceptor agonist, and to trifluoromethylphenylpiperazine (TFMPP; 1, 2 and 5 mg/kg s.c.), a putative serotonergic 5-hydroxytryptamine-1B receptor agonist. Obese Zucker rats had significantly lower concentrations of 5-hydroxyindoleacetic acid, the main deaminated metabolite of 5-hydroxytryptamine, in the nucleus paraventricularis (PVN) and in the nucleus ventromedialis (VMN), when compared to their lean littermate controls. The rate of accumulation of 5-hydroxytryptophan after decarboxylase inhibition was reduced in the PVN, nucleus supraopticus, nucleus periventricularis and nucleus suprachiasmaticus of the obese rats. No differences were observed in basal concentrations of norepinephrine, dopamine or 3,4-dihydroxyphenylacetic acid between obese and lean Zucker rats in the brain areas studied. However, the rate of accumulation of 3,4-dihydroxyphenylalanine was lower in the VMN and in the median eminence of the obese rats. The feeding behavioral tests showed significantly augmented hyperphagic responses to clonidine in obese Zucker rats. The anorexic effect of TFMPP was similar in both phenotypes. It is concluded that serotonergic activity is reduced in obese Zucker rats, particularly in the PVN, which plays a key role in the control of feeding behavior. The reduced serotonergic activity may be associated with enhanced alpha 2-adrenoceptor-mediated feeding responses in obese Zucker rats.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗

PubMed1990

Use of inflammatory cell activities in bovine milk to diagnose mastitis.

The activity of leukocytes, determined by chemiluminescence (CL) emission, was compared with the somatic cell count (SCC) in 4,883 quarter-milk samples from 132 dairy cows. The presence of bacteria was determined by bacteriologic culture of samples in which SCC and CL were high. Chemiluminescence was measured with an automated illuminometer system at 37 C after separating the leukocytes from milk by allowing them to adhere to cotton-wool swabs. Chemiluminescence emission was induced by opsonized zymosan and enhanced by luminol. After luminol and zymosan were added to the measuring vials containing the swabs, CL emission increased rapidly, reaching its maximum usually at about 15 minutes of reaction time, and decreasing slowly thereafter. In general, good correlation was found between CL and SCC (r = 0.876; P less than or equal to 0.001; n = 4,883). Even milk samples with low SCC gave reliably measurable CL signals. Minor pathogens in the milk caused about a sevenfold increase in both SCC and CL, whereas major pathogens caused 14- and 25-fold increases in SCC and CL, respectively. The diagnostic situation that requires both sensitivity and specificity to be at least 90% was attained only by the CL assay for major pathogens. These results suggest that the measurement of milk leukocyte activity by CL assay applies well to the diagnosis of mastitis, and has the potential to become a large-scale laboratory test, as well as a simple cowside test.

Animals↗

PubMed1988

Chronic treatment with SCH 23390, a selective dopamine D-1 receptor antagonist, decreases dopamine metabolism in rat caudate nucleus.

Chronic treatment (18 days; 0.1 and 0.5 mg/kg per day) with the selective dopamine (DA) D-1 receptor antagonist, SCH 23390, significantly reduced the concentration of homovanillic acid (HVA) and the ratios of HVA/DA and DOPAC/DA in the nucleus caudatus of the rat but did not change the metabolism of DA in the prefrontal cortex, substantia nigra or the A10 area. Furthermore, the concentrations of noradrenaline were dose dependently decreased in the A10 area during SCH 23390 treatment. It is concluded that chronic DA D-1 receptor blockade causes changes in the metabolism of DA similar to those caused by classical neuroleptics.

3,4-Dihydroxyphenylacetic Acid↗