Selective Decrease (selective + decrease)

Distribution by Scientific Domains

Selected Abstracts

Substance induced plasticity in noradrenergic innervation of the paraventricular hypothalamic nucleus

Arthur S. P. Jansen
Abstract Single administration of the cytokine interleukin-1, (IL-1), or the psychostimulant amphetamine, enhanced adrenocorticotropin hormone and corticosterone responses to a stress challenge weeks later. This long-lasting hypothalamic-pituitary-adrenal (HPA)-sensitization is paralleled by an increase in electrically evoked release of noradrenaline in the paraventricular hypothalamic nucleus (PVN). We hypothesized that these functional changes may be associated with morphological plasticity of noradrenergic projections to the PVN, a parameter that shows high reproducibility. Specific alterations in relative (nor)adrenergic innervation density were studied by using dopamine-,-hydroxylase (DBH) as a marker. An image analysis system was used to detect changes in the relative DBH innervation density of the PVN. Groups of adult male rats were given IL-1 (10 g/kg i.p.), amphetamine (5 mg/kg i.p.), or saline. Three weeks later, IL-1 and amphetamine primed rats showed enhanced adrenocorticotropin hormone and corticosterone responses to an amphetamine challenge. In another set of experiments, the relative DBH innervation density was measured in different PVN subnuclei at four rostro-caudal levels. Single administration of either IL-1 or amphetamine causes three weeks later a selective decrease in relative DBH innervation density in those subnuclei of the PVN that contain high numbers of corticotrophin-releasing hormone (CRH) producing neurons: the dorsal parvocellular and medial parvocellular PVN. We conclude that (1) long-lasting sensitization induced by single exposure to IL-1 and amphetamine induces specific pattern of neuroplastic changes in (nor)adrenergic innervation in the PVN and (2) reduction of relative DBH innervation density in CRH-rich areas is associated with paradoxical increase of electrically evoked release of (nor)adrenaline. [source]


EVOLUTION, Issue 12 2002
Peter Crnokrak
Abstract., Inbreeding depression, the reduction in fitness that accompanies inbreeding, is one of the most important topics of research in evolutionary and conservation genetics. In the recent literature, much attention has been paid to the possibility of purging the genetic load. If inbreeding depression is due to deleterious alleles, whose effect on fitness are negative when in a homozygous state, then successive generations of inbreeding may result in a rebound in fitness due to the selective decrease in frequency of deleterious alleles. Here we examine the experimental evidence for purging of the genetic load by collating empirical tests of rebounds in fitness-related traits with inbreeding in animals and plants. We gathered data from 28 studies including five mammal, three insect, one mollusc, and 13 plant species. We tested for purging by examining three measures of fitness-component variation with serial generations of inbreeding: (1) changes in inbreeding depression, (2) changes in fitness components of inbred lines relative to the original outbred line, and (3) purged population (outcrossed inbred lines) trait means as a function of ancestral outbred trait means. Frequent and substantial purging was found using all three measures, but was particularly pronounced when tracking changes in inbreeding depression. Despite this, we found little correspondence between the three measures of purging within individual studies, indicating that the manner in which a researcher chooses to estimate purging will affect interpretation of the results obtained. The discrepancy suggests an alternative hypothesis: rebounds in fitness with inbreeding may have resulted from adaptation to laboratory conditions and not to purging when using outcrossed inbred lines. However, the pronounced reduction in inbreeding depression for a number of studies provides evidence for purging, as the measure is likely less affected by selection for laboratory conditions. Unlike other taxon-specific reviews on this topic, our results provide support for the purging hypothesis, but firm predictions about the situations in which purging is likely or the magnitude of fitness rebound possible when populations are inbred remain difficult. Further research is required to resolve the discrepancy between the results obtained using different experimental approaches. [source]

Blunted Pituitary-Adrenocortical Stress Response in Adult Rats Following Neonatal Dexamethasone Treatment

K. Felszeghy
Abstract Glucocorticoids have a prominent impact on the maturation of the stress-related neuroendocrine system and on the postnatal establishment of adaptive behaviour. The present study aimed at investigating the stress responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone. Newborn male Wistar rats were injected s.c. with 1 g/g dexamethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (ACTH) and corticosterone concentrations were measured in the resting state and following a 30-min cold stress at the age of 10 days, as well as after a 30-min restraint stress at the age of 14 weeks. Also in adults, pituitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 g/kg corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities were assessed in the pituitaries of adult rats. The results showed that at day 10 basal ACTH concentration was elevated while the cold stress-evoked ACTH response was attenuated in the dexamethasone-treated rats. As adults, treated rats showed a suppressed elevation of both ACTH and corticosterone plasma cncentrations in response to restraint, while basal hormonal concentrations were not altered. There was no difference in the magnitude of the CRH-induced elevation of ACTH and corticosterone concentrations initially; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone treatment strongly suppressed body weight gain, and adrenal and thymus weights in the early phase of postnatal development. By adulthood, the body and adrenal weights were normalized while thymus weight was greater than in controls. These findings indicate that neonatal dexamethasone treatment permanently alters HPA axis activity by reducing stress responses to cold and restraint probably through supra-pituitary actions, and by decreasing the effectiveness of feedback through a diminished GR binding in the pituitary. [source]

Inhibition of neural activity depletes orexin from rat hypothalamic slice culture

Shotaro Michinaga
Abstract Orexins (hypocretins) are neuropeptides produced by a small population of hypothalamic neurons whose dysregulation may lead to narcolepsy, a neurological disorder characterized by disorganization of sleep and wakefulness. Excessive stimulation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors causes preferential loss of orexin neurons in the hypothalamus, whereas an adequate level of neuronal excitatory activities is generally known to be important for the maintenance of central neurons. By examining the effect of manipulation of neural activity, we found that 24,72 hr application of tetrodotoxin (TTX) caused a substantial decrease in the number of orexin-immunoreactive neurons, but not of melanin-concentrating hormone-immunoreactive neurons, in hypothalamic slice culture. Similar results were obtained when neural activity was arrested by added extracellular Mg2+. Reduction of orexin expression by TTX and Mg2+ was also observed at mRNA level. The decrease of orexin-immunoreactive neurons was attributable to depletion of orexin, because it was reversible after washout of TTX or elevated extracellular Mg2+ and was not associated with induction of cell death. Blockers of voltage-dependent Ca2+ channels as well as of NMDA receptors also induced a significant and selective decrease of orexin-immunoreactive neurons. Moreover, TTX-induced decrease of orexin immunoreactivity was largely abrogated by concurrent application of a moderate concentration of NMDA. These results suggest that Ca2+ entry associated with nontoxic levels of spontaneous activity of glutamatergic inputs plays an important role in the maintenance of orexin neurons in a tissue culture model. 2009 Wiley-Liss, Inc. [source]

Arabidopsis XXT5 gene encodes a putative ,-1,6-xylosyltransferase that is involved in xyloglucan biosynthesis

Olga A. Zabotina
Summary The function of a putative xyloglucan xylosyltransferase from Arabidopsis thaliana (At1g74380; XXT5) was studied. The XXT5 gene is expressed in all plant tissues, with higher levels of expression in roots, stems and cauline leaves. A T-DNA insertion in the XXT5 gene generates a readily visible root hair phenotype (root hairs are shorter and form bubble-like extrusions at the tip), and also causes the alteration of the main root cellular morphology. Biochemical characterization of cell wall polysaccharides isolated from xxt5 mutant seedlings demonstrated decreased xyloglucan quantity and reduced glucan backbone substitution with xylosyl residues. Immunohistochemical analyses of xxt5 plants revealed a selective decrease in some xyloglucan epitopes, whereas the distribution patterns of epitopes characteristic for other cell wall polysaccharides remained undisturbed. Transformation of xxt5 plants with a 35S::HA-XXT5 construct resulted in complementation of the morphological, biochemical and immunological phenotypes, restoring xyloglucan content and composition to wild-type levels. These data provide evidence that XXT5 is a xyloglucan ,-1,6-xylosyltransferase, and functions in the biosynthesis of xyloglucan. [source]

Absence of a classically activated macrophage cytokine signature in peripheral spondylarthritis, including psoriatic arthritis,

Bernard Vandooren
Objective Peripheral spondylarthritis (SpA) is characterized by macrophages that express CD163, a marker of alternative activation (M2). The purpose of this study was to assess whether this differential infiltration with macrophage subsets was associated with a different local inflammatory milieu in SpA as compared with rheumatoid arthritis (RA). Methods The effect of SpA and RA synovial fluid (SF) on macrophage polarization was tested in vitro on normal peripheral blood monocytes. SF levels of classically activated macrophage (M1),derived and alternatively activated macrophage (M2),derived mediators were analyzed by enzyme-linked immunosorbent assay and multiparameter Luminex bead assay in 47 patients with non-psoriatic SpA, 55 with RA, and 15 with psoriatic arthritis (PsA). Paired synovial biopsy samples were analyzed histologically. Results SF from SpA patients promoted preferential expression of the M2 markers CD163 and CD200R in vitro, even if SF levels of the prototypical M2-polarizing factors (interleukin-4 [IL-4], IL-13, and IL-10) were not increased as compared with those in RA SF. Despite a similar degree of overall joint inflammation in SpA and RA, SpA synovitis displayed strongly reduced SF levels of M1-derived, but not M2-derived, mediators, such as tumor necrosis factor , (TNF,), IL-1,, IL-12p70, and interferon-,,inducible protein 10. SF levels of M1-derived mediators correlated well with peripheral joint inflammation in RA, but neither these mediators nor IL-1, and IL-17 did so in SpA. Of interest, the SF cytokine profile in PsA, a more destructive subtype of SpA, was similar to that in non-psoriatic SpA. Conclusion The local inflammatory milieu is clearly different in SpA as compared with RA peripheral arthritis. Synovitis in SpA, including that in PsA, is characterized by a selective decrease in M1-derived proinflammatory mediators, such as TNF, and IL-1,. [source]

Fustin flavonoid attenuates ,-amyloid (1,42)-induced learning impairment

Chun-Hui Jin
Abstract Natural flavonoids ameliorate amyloid-, peptide (A,)-induced neurotoxicity. We examined whether the fustin flavonoid affects A,-induced learning impairment in mice. Repeated treatment with fustin significantly attenuated A, (1,42)-induced conditioned fear and passive avoidance behaviors. This effect was comparable to that of EGb761, a standard extract of ginkgo. Fustin treatment significantly prevented decreases in acetylcholine (ACh) levels, choline acetyltransferase (ChAT) activity, and ChAT gene expression induced by A, (1,42). Fustin also consistently suppressed increases in acetyl cholinesterase (AChE) activity and AChE gene expression induced by A, (1,42). In addition, fustin significantly attenuated A, (1,42)-induced selective decreases in muscarinic M1 receptor gene expression and muscarinic M1 receptor binding activity (as determined by [3H]pirenzepine binding) by modulating extracellular signal-regulated kinase 1/2 (ERK 1/2) and cAMP response-element binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression. These effects of fustin were reversed by treatment with dicyclomine, a muscarinic M1 receptor antagonist, and SL327, a selective ERK inhibitor, but not by chelerythrine, a pan-protein kinase C (PKC) inhibitor. Taken together, our results suggest that fustin attenuates A, (1,42)-impaired learning, and that the ERK/CREB/BDNF pathway is important for the M1 receptor-mediated cognition-enhancing effects of fustin. 2009 Wiley-Liss, Inc. [source]

CSF amyloid-, 1-38 and 1-42 in FTD and AD: Biomarker performance critically depends on the detergent accessible fraction

Mirko Bibl Dr.
Abstract Cerebrospinal fluid (CSF) A,1-38, A,1-40, and A,1-42 were comparatively analyzed by amyloid-beta SDS-PAGE with Western immunoblot (A,-SDS-PAGE/immunoblot), electrochemiluminescence detection and ELISA (MSD/ELISA) in patients with Alzheimer's disease (AD, n,=,40), frontotemporal dementia (FTD, n,=,30), and other dementias (n,=,50) and nondemented disease controls (n,=,30). CSF A,-peptide concentrations were higher and selective decreases of CSF A,1-38 in FTD and A,1-42 in AD were more evident as measured after SDS-denaturizing of samples by A,-SDS-PAGE/immunoblot. The SDS-accessible pool of CSF A,1-38 and A,1-42, represented by the individual gain of A,-peptide yield using A,-SDS-PAGE/immunoblot, was reduced in both FTD and AD. Accordingly, biomarker accuracies of A,1-38 and A,1-42 for detection of FTD and AD, respectively declined as determined by MSD/ELISA. We conclude that a pool of CSF A,1-38 and A,1-42, which shows disease-specific reductions in FTD and AD, may be bound to carriers and can be released by SDS. Assessing this SDS-accessible A,-peptide pool may crucially enhance the accuracy of CSF biomarker tests. Identifying disease-specific binding properties of affected A, carriers may elucidate pathogenic aspects and open up a novel field for therapeutic approaches. [source]