The role of the anteriolateral bed nucleus of the stria terminalis in stress-induced nociception

Activation of the central amygdala (CeA) by corticosterone (CORT) induces somatic and colonic hypersensitivity through corticotrophin-releasing factor (CRF)-dependent mechanisms. However, the importance of the bed nucleus of the stria terminalis (BNST), part of the extended amygdala, on nociception remains unexplored. In the present study, we test the hypothesis that stimulation of the CeA by CORT induces somatic and colonic hypersensitivity through activation of the anteriolateral BNST (BNST(AL)). Animals were implanted with micropellets of CORT or cholesterol (CHOL) onto the CeA or the BNST(AL). Mechanical sensitivity was quantified using electronic von Frey filaments, and colonic nociception was measured by quantifying a visceromotor response to graded colorectal distension. In situ hybridization was used to determine mRNA levels for CRF, CRF(1), and CRF(2) receptors in the BNST(AL). In a second group, animals were implanted bilaterally with 1) CORT or CHOL micropellets onto the CeA; and 2) cannulas localized to the BNST(AL) to administer a CRF(1) receptor antagonist (CP376395). Animals implanted with CORT onto the CeA, but not the BNST(AL), exhibited increased expression of CRF mRNA and increased CRF(1)-to-CRF(2) receptor ratio in the BNST, as well as somatic and colonic hypersensitivity compared with CHOL controls. Infusion of CP376395 into the BNST(AL) inhibited somatic and colonic hypersensitivity in response to elevated amygdala CORT. Somatic and colonic hypersensitivity induced by elevated amygdala CORT is mediated via a CRF(1) receptor-dependent mechanism in the BNST(AL). The CeA through a descending pathway involving the BNST(AL) plays a pivotal role in somatic and colonic nociception.     

Alterations in the anterior hypothalamic dopamine system in aggressive adolescent AAS-treated hamsters

Anabolic androgenic steroid (AAS) treatment throughout adolescence facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The present study was conducted to investigate the role of the dopaminergic system in the modulation of AAS-induced aggressive behavior. Hamsters were administered AAS during adolescence, scored for offensive aggression using the resident-intruder paradigm, and then examined for alterations in DA immunoreactivity in brain regions implicated in the aggressive phenotype, including the anterior hypothalamus (AH), the bed nucleus of the stria terminalis (BNST), the medial and central amygdala (MeA and CeA), the lateral septum (LS) and the ventrolateral hypothalamus (VLH). When compared with non-aggressive sesame-oil-treated controls, aggressive AAS-treated animals showed increased tyrosine hydroxylase immunoreactivity in anterior hypothalamic subnuclei, namely the nucleus circularis (NC) and medial supraoptic nucleus (mSON). In addition, AAS-treated animals showed altered D₂ receptor expression in the AH and the VLH, as measured by D₂-immunoreactivity. Together these results suggest that alterations in DA synthesis and function together with modifications in D₂ receptor expression in the AH may underlie neuroplastic events which facilitate AAS-induced aggression.     

Nutritive value of lentil and vetch straws as compared with alfalfa hay and wheat straw for replacement ewe lambs

The objective of this study was to compare the nutritive value of lentil straw (LS) and vetch straws (VS) with alfalfa hay (AH) and wheat straw (WS). Forty Awassi ewes (body weight (BW)=56.2 kg) were assigned randomly to four dietary treatments (10 ewes per treatment) for 6 weeks using a complete randomize design. In each dietary treatment, ewes were fed 550 g per day of concentrate mix formulated to supply 40% of the metabolizable energy requirement. After the consumption of the concentrate mix, ewes had ad libtum access to AH, LS, VS, or WS. Forage intake, total dry matter intake (DMI), and organic matter intake (OMI) were higher for AH and LS and lowest for WS. Final weight of ewes fed AH and LS diets were higher (P<0.05) than VS and WS diets. However, ewes fed VS diet gained more weight (2.5 kg) than ewes on WS diet (0.2 kg). Dry matter digestibility was higher for the AH and LS diets (59.4%), and lowest for WS diet (49.6%). The VS diet had an intermediate value (54.4%). Ruminal passage rate was higher for AH and LS (3.4% per hour) compared with WS (1.9% per hour). Eating time for the AH diet was lowest compared with the rest of the forages. Eating time, expressed as minutes per kilogram NDF intake, was highest for WS and VS diets (680 min) compared with AH and LS diets (535 min). WS diet required more time for rumination (395 min per day) compared to AH, LS, and VS diets. However, ewes on VS diet spent more time ruminating per kilogram NDF consumed (954 min) compared with WS, LS, and AH diets (901, 617, and 597 min, respectively). These results were significant and demonstrate that the nutritive value of LS is greater than VS and close to the nutritive value of AH. VS nutritive value is slightly greater than WS.     

Basal leaf senescence in a sunflower (Helianthus annuus) canopy: responses to increased R/FR ratio

Senescence of lower leaves (LS) begins before anthesis in sunflower crop canopies. Using isolated field-grown sunflower plants, it has previously been shown that pre-anthesis LS is dependent on photosynthetic photon flux density (PPFD) and is hastened by increases in far-red light. We tested the hypothesis that increasing the red/far-red ratio (R/FR) perceived by basal leaves within canopies delays LS. To do this, light impinging on the lower surface of north-oriented 8th leaves (cotyledons=0) of crops with maximum leaf area indexes of 3.3 (Experiment 1) and 2.4 (Experiment 2) was enriched (+8.33 μmol m⁻² s⁻¹) with red light using light emitting diode (LED) panels. LED panels constructed with unlit LED or with green LED (PPFD slightly greater than the red LED panels, to compensate for lower efficiency) were used as controls. Compared with controls, additional R significantly ( P <0.05) increased R/FR perceived by the lower surface and significantly ( P <0.01) delayed LS. On average, leaf duration, as time between full expansion and a 70% diminution of chlorophyll content, was 5 days greater for leaves receiving extra red light (maximum observed LD=27 days). We conclude that an increase in the R/FR ratio can delay LS in crop canopies.     

Effect of photoperiod on vasopressin-induced aggression in Syrian hamsters

Syrian hamsters are photoperiodic and become sexually quiescent when exposed to short "winter-like" photoperiods. In short photoperiods, male hamsters display significantly higher levels of aggression than males housed in long photoperiods. Arginine-vasopressin (AVP) within the anterior hypothalamus (AH) has been reported to modulate aggression in hamsters housed in long photoperiods. Previous studies have shown that AVP can facilitate aggression and its effects appear to be mediated by AVP V(1a) receptors (V(1a)R). In the present study, we investigated whether the increased levels of aggression observed after exposure to short photoperiod were the result of an increased responsiveness to AVP within the AH. Injections of AVP into the AH significantly increased aggression in hamsters housed in a long photoperiod, but had no effect in hamsters housed in a short photoperiod. In addition, injection of a V(1a)R antagonist into the AH significantly inhibited aggression in hamsters housed in long photoperiod, but had no effect in hamsters housed in a short photoperiod. These findings indicate that AVP within the AH increases aggression in hamsters housed in long photoperiods, but not in hamsters housed in short photoperiods.     

Evidence of lasting dysregulation of neuroendocrine and HPA axis function following global cerebral ischemia in male rats and the effect of Antalarmin on plasma corticosterone level

Abnormal function of the neuroendocrine stress system has been implicated in the behavioral impairments observed following brain ischemia. The current study examined long-term changes in stress signal regulation 30 days following global cerebral ischemia. Experiment 1 investigated changes in the expression of corticotropin releasing hormone (CRH) and its subtype 1 receptor (CRHR1), glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus (PVN), the central nucleus of the amygdala (CeA), and the CA1 subfield of the hippocampus. Tyrosine hydroxylase (TH) was determined at the locus coeruleus (LC). Experiment 2 investigated the role of central CRHR1 activation on corticosterone (CORT) secretion at multiple time intervals following global ischemia after exposure to an acute stressor. Findings from Experiment 1 demonstrated a persistent increase in GR, CRH and CRHR1 immunoreactivity (ir) at the PVN, reduced GR and CRHR1 expression in pyramidal CA1 neurons, and increased LC TH expression in ischemic rats displaying working memory errors in the radial arm Maze. Findings from Experiment 2 revealed increased CORT secretion up to 7 days, but no longer present 14 and 21 days post ischemia. However upon an acute restraint stress induced 27 days following reperfusion, ischemic rats had increased plasma CORT secretions compared to sham-operated animals, suggesting HPA axis hypersensitivity. Antalarmin (2 μg/2 μl) pretreatment significantly attenuated post ischemic elevation of basal and stress-induced CORT secretion. These findings support persistent neuroendocrine dysfunctions following brain ischemia likely to contribute to emotional and cognitive impairments observed in survivors of cardiac arrest and stroke.     

Subunit interactions at the V1-Vo interface in yeast vacuolar ATPase

Eukaryotic vacuolar ATPase (V-ATPase) is regulated by a reversible dissociation mechanism that involves breaking and reforming of protein-protein interactions at the interface of the V(1)-ATPase and V(o)-proton channel domains. We found previously that the head domain of the single copy C subunit (C(head)) binds one subunit EG heterodimer with high affinity (Oot, R.A. and Wilkens, S. (2010) J. Biol. Chem. 285, 24654-24664). Here we generated a water-soluble construct of the N-terminal domain of the V(o) "a" subunit composed of amino acid residues 104-372 (a(NT(104-372))). Analytical gel filtration chromatography and sedimentation velocity analysis revealed that a(NT(104-372)) undergoes reversible dimerization in a concentration-dependent manner. A low-resolution molecular envelope was calculated for the a(NT(104-372)) dimer using small angle x-ray scattering data. Isothermal titration calorimetry experiments revealed that a(NT(104-372)) binds the C(foot) and EG heterodimer with dissociation constants of 22 and 33 μM, respectively. We speculate that the spatial closeness of the a(NT), C(foot), and EG binding sites in the intact V-ATPase results in a high-avidity interaction that is able to resist the torque of rotational catalysis, and that reversible enzyme dissociation is initiated by breaking either the a(NT(104-372))-C(foot) or a(NT(104-372))-EG interaction by an as-yet unknown signaling mechanism.     

Differences in corticosterone level due to inter-food interval length: implications for schedule-induced polydipsia

The purpose of this study was to determine the effects of different food-reinforcement schedules on plasma corticosterone (CORT), and its possible involvement in the acquisition and maintenance of schedule-induced polydipsia (SIP). In Experiment 1, three groups of rats were submitted to two different fixed-interval (FI) schedules with inter-food intervals of 30 and 120 s, and to a massed-feeding presentation for 40 days until SIP was well stabilized. In Experiment 2, six groups of rats were exposed to the same schedules, FI 30s and FI 120s, and to the massed-feeding condition, but no water bottles were presented. CORT levels were determined on Days 3 and 40. Results of Experiment 1 indicated that FI 30s schedule, but not FI 120s or the massed-feeding condition, induces excessive drinking from Day 3. Results in Experiment 2 indicated that CORT levels were similar for all the groups on Day 3. However, only animals on the FI 30s schedule did increase their CORT levels on Day 40, with no variation in the hormone in the other two conditions, FI 120s and massed-feeding presentations. The data are discussed in terms of the implications of these results for hypotheses of SIP as anxiolitic behavior.     

Regulation of neurotensin receptor function by the arachidonic acid-lipoxygenase pathway in prostate cancer PC3 cells

Neurotensin (NT) elevates leukotriene levels in animals and stimulates 5-HETE formation in prostate cancer PC3 cells. PC3 cell growth is stimulated by NT and inhibited by lipoxygenase (LOX) blockers. This led us to test LOX blockers (NDGA, MK886, ETYA, Rev5901, AA861 and others) for effects on NT binding and signaling. LOX blockers dramatically enhanced 125I-neurotensin binding to NT receptor NTR1 in PC3 cells, whereas they inhibited NT-induced inositol phosphate formation. These effects were indirect (binding to isolated membranes was unaffected), receptor-specific (binding to beta2-adrenergic, V1a-vasopressin, EGF and bombesin receptor was unaffected) and pathway-specific (cyclooxygenase inhibitors were inactive). NT receptor affinity was increased but receptor number and % internalization were unchanged. Also supporting the involvement of arachidonic acid metabolism in NTR1 regulation was the finding that inhibitors of PLA2 and DAG lipase enhanced NT binding. These findings suggest that NTR1 is regulated by specific feedback mechanism(s) involving lipid peroxidation and/or LOX-dependent processes.     

Comparison of neurotensin levels, receptors and actions in LS/Ibg and SS/Ibg mice

Neurotensin (NT), injected centrally, markedly enhances sensitivity to ethanol-induced anesthesia in SS but not in LS mice (4). Since LS and SS mice were bred selectively for differential sensitivity to ethanol, these findings suggest that neurotensinergic neuronal processes mediate some of ethanol's actions and that LS and SS mice might differ genetically in neurotensinergic systems. Indeed, in biochemical studies it was shown that LS and SS mice differ in NT-like immunoreactivity in specific brain regions, i.e., hypothalamus, and in NT receptor densities (Bmax) in frontal cortex and striatum. In other experiments LS and SS mice differed in behavioral responses to centrally administered NT. Intracerebroventricular (ICV) administration of NT produced dose-dependent changes in motor activity, hypothermia, and analgesia in both LS and SS mice. SS mice appeared to be more sensitive than LS to NT-induced analgesia but not hypothermia. Neurotensin increased or decreased locomotor activity in both SS and LS mice following intraventral tegmental area or ICV administration, respectively. The results indicate that LS and SS mice, which were selectively bred for differences in ethanol sensitivity, differ genetically in NT concentrations, receptor densities in specific brain regions, and in some receptor-mediated behavioral responses to NT.     

Interaction effects of corticosterone and experience on aggressive behavior in the green anole lizard

Aggressive encounters are accompanied by a release of stress hormone, and this corticosterone (CORT) secretion could influence aggressive behavior in subsequent encounters. We investigated the modulating effects of CORT on aggressive behavior in the context of a 5-day social experience in male green anole lizards. In Experiment 1, we measured plasma CORT levels in animals that were exposed for different times to aggressive males. In Experiment 2, using metyrapone, a CORT synthesis blocker, we tested whether CORT secretion in response to the aggressive stimulus plays a role in experience-dependent facilitation of aggressive behavior. We hypothesized that aggressive encounters would increase plasma CORT levels, and that blocking CORT synthesis with metyrapone treatment during the aggressive encounter would cause an animal to become more aggressive. We also tested whether blocking CORT would interfere with the influence of 5-day social experience on animals' behavior in a subsequent aggressive encounter. Animals that were exposed to another male showed higher plasma CORT levels immediately after the 10 min encounter than animals exposed to the non-social video, and this high level was maintained through day 5. Within the aggressive video groups, in Experiment 2, there was a distinctly different pattern in displays depending on drug condition: vehicle-injected animals showed gradual increases followed by decreases in aggressive behavioral responses to the video as the five days proceeded (habituation), while animals injected with metyrapone started out with high aggressive behavior and did not decrease behavioral responses at later trials (no habituation). Finally, when tested with a novel conspecific on day 6, animals previously injected with metyrapone showed no higher aggression than did animals previously injected with vehicle and exposed to the aggressive video. These results suggest that blocking CORT synthesis during the exposure to the aggressive video induced animals to remain aggressive toward the repetitive stimulus without habituating, while not becoming more aggressive than controls toward a novel challenger.     

Protective effects of dihydromyricetin on primary hippocampal astrocytes from cytotoxicity induced by comorbid diabetic neuropathic pain and depression

Activated astrocytes play a key role in diabetic neuropathic pain and depression. We aimed to assess the protective effects of dihydromyricetin (DHM) on primary hippocampal astrocytes cultured with high glucose (HG), substance P (SP), and corticosterone (CORT). Culturing with HG + SP + CORT resulted in damage to primary hippocampal astrocytes, which simulates the clinical damage caused by comorbidity of diabetic neuropathic pain and depression. Western blot, qPCR, and immunofluorescence analyses revealed that HG + SP + CORT increased P2X₇ receptor expression in primary hippocampal astrocytes, which was reversed by DHM treatment. Further, HG + SP + CORT elevated TNF-α, IL-1β, free Ca²⁺, and ERK1/2 phosphorylation levels, which was inhibited by DHM or P2X₇ shRNA treatment. Moreover, DHM significantly reduced the P2X₇ agonist-activated currents in HEK293 cells transfected with the P2X₇ receptor. These findings suggest that DHM can protect primary hippocampal astrocytes cultured with HG + SP + CORT from P2X₇ receptor-mediated damage. Culturing cells with HG + SP + CORT might be a viable cell model for cellular injury exploration of diabetic comorbid pain and depression.

     

Juxtamembrane region of the amino terminus of the corticotropin releasing factor receptor type 1 is important for ligand interaction

The functional properties of the amino terminus (NT) of the corticotropin releasing factor (CRF) receptor type 1 (R1) were studied by use of murine (m) CRFR1 and rat (r) parathyroid hormone (PTH)/parathyroid hormone-related peptide receptor (PTH1R) chimeras. The chimeric receptor CXP, in which the NT of mCRFR1 was annealed to the TMs of PTH1R, and the reciprocal hybrid, PXC, bound radiolabeled analogues of sauvagine and PTH(3--34), respectively. Neither hybrid bound radiolabeled CRF or PTH(1--34). CRF and PTH(1--34) weakly stimulated intracellular cAMP accumulation in COS-7 cells transfected with PXC and CXP, respectively. Thus the NT is required for ligand binding and the TMs are required for agonist-stimulated cAMP accumulation. Replacing individual intercysteine segments of PXC with their mCRFR1 counterparts did not rescue CRF or sauvagine radioligand binding or stimulation of cAMP accumulation. Replacement of residues 1--31 of mCRFR1 with their PTH1R counterparts resulted in a chimeric receptor, PEC, which had normal CRFR1 functional properties. In addition, a series of chimeras (F1PEC--F6PEC) were generated by replacement of the NT intercysteine residues of PEC with their PTH1R counterparts. Only F1PEC, F2PEC, and F3PEC showed detectable CRF and sauvagine radioligand binding. All of the PEC chimeras except F5PEC increased cAMP accumulation. These data indicate that the Cys(68)(-)Glu(109) domain is important for binding and that the Cys(87)(-)Cys(102) region plays an important role in CRFR1 activation.     

Short-term fasting affects locomotor activity,corticosterone, and corticosterone binding globulin in a migratory songbird

Unpredictable events such as severe storms lead to an increase in circulating corticosterone (CORT) in breeding birds. This increase is often accompanied by elevations in foraging and irruptive behavior. We were interested in determining if acute food restriction (such as might occur during inclement weather) is a sufficient cue to elicit an increase in locomotor activity, increase CORT secretion, and/or decrease circulating levels of corticosterone binding globulin (CBG) in white-crowned sparrows (Zonotrichia leucophrys gambelii). Male Z.l. gambelii were housed individually in environmental chambers on long days (LD 20:4) to simulate breeding season daylength. Birds were fed ad libitum, and on select days, food was removed 2 h after lights on (fasted treatment), or was removed and replaced (control). We analyzed CORT and CBG levels after 1, 2, 6, 22 (lights on), and 23 h under fasted and control conditions. We also measured activity during the 23-h experiment. Activity levels were increased under fasted conditions during the daytime relative to control conditions, but activity levels did not differ between treatments during the night. Fasting as little as 1, 2, and 6 h significantly increased total CORT levels above baseline (control), although after 22 h, total CORT levels under fasted conditions matched those under control conditions. Plasma CBG decreased after the 22-h fast, and remained low after the 23-h fast. This change was sufficient to significantly elevate free CORT levels in fasted birds relative to ad libitum food conditions, despite the lack of difference in total CORT levels.     

Analysis of interactions responsible for vasopressin binding to human neurohypophyseal hormone receptors-molecular dynamics study of the activated receptor-vasopressin-G(alpha) systems.

Vasopressin (CYFQNCPRG-NH(2), AVP) is a semicyclic endogenous peptide, which exerts a variety of biological effects in mammals. The main physiological roles of AVP are the regulation of water balance and the control of blood pressure and adrenocorticotropin hormone (ACTH) secretion, mediated via three different subtypes of vasopressin receptors: V1a, V1b and V2 receptors (V1aR, V1bR and V2R, respectively). They are the members of the class A, G-protein-coupled receptors (GPCRs). AVP also modulates several behavioral and social functions. In this study, the interactions responsible for AVP binding to vasopressin V1a and V2 receptors versus the closely related oxytocin ([I3,L8]AVP, OT) receptor (OTR) have been investigated. Three-dimensional models of the activated receptors were constructed using multiple sequence alignment, followed by homology modeling using the complex of activated rhodopsin with Gt(alpha) C-terminal peptide of transducin MII-Gt(338-350) prototype as a template. AVP was docked into the receptor-G(alpha) systems. The three lowest-energy pairs of receptor-AVP-G(alpha) (two complexes per each receptor) were selected. The 1-ns unconstrained molecular dynamics (MD) of complexes embedded into the fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) lipid bilayer was conducted in the AMBER 7.0 force field. Six relaxed receptor-AVP-G(alpha) models were obtained. The residues responsible for AVP binding to vasopressin receptors have been identified and a different mechanism of AVP binding to V2R than to V1aR has been proposed.     

Local perfusion of corticosterone in the rat medial hypothalamus potentiates d-fenfluramine-induced elevations of extracellular 5-HT concentrations

The dorsomedial hypothalamus (DMH) plays an important role in coordinating physiological and behavioral responses to stress-related stimuli. In vertebrates, DMH serotonin (5-HT) concentrations increase rapidly in response to acute stressors or corticosterone (CORT). Recent studies suggest that CORT inhibits postsynaptic clearance of 5-HT from the extracellular fluid in the DMH by blocking organic cation transporter 3 (OCT3), a polyspecific CORT-sensitive transport protein. Because OCTs are low-affinity, high-capacity transporters, we hypothesized that CORT effects on extracellular 5-HT are most pronounced in the presence of elevated 5-HT release. We predicted that local application of CORT into the DMH would potentiate the effects of d-fenfluramine, a 5-HT-releasing agent, on extracellular 5-HT. These experiments were conducted using in vivo microdialysis in freely-moving male Sprague-Dawley rats implanted with a microdialysis probe into the medial hypothalamus (MH), which includes the DMH. In Experiment 1, rats simultaneously received intraperitoneal (i.p.) injections of 1 mg/kg d-fenfluramine or saline and either 200 ng/mL CORT or dilute ethanol (EtOH) vehicle delivered to the MH by reverse-dialysis for 40 min. In Experiment 2, 5 μM d-fenfluramine and either 200 ng/mL CORT or EtOH vehicle were concurrently delivered to the MH for 40 min using reverse-dialysis. CORT potentiated the increases in extracellular 5-HT concentrations induced by either i.p. or intra-MH administration of d-fenfluramine. Furthermore, CORT and d-fenfluramine interacted to alter home cage behaviors. Our results support the hypothesis that CORT inhibition of OCT3-mediated 5-HT clearance from the extracellular fluid contributes to stress-induced increases in extracellular 5-HT and 5-HT signaling.     

Insulin-like growth factor-1 receptor transactivation modulates the inflammatory and proliferative responses of neurotensin in human colonic epithelial cells

Neurotensin (NT) is a gastrointestinal neuropeptide that modulates intestinal inflammation and healing by binding to its high-affinity receptor NTR1. The dual role of NT in inflammation and healing is demonstrated in models of colitis induced by Clostridium difficile toxin A and dextran sulfate sodium, respectively, and involves NF-κB-dependent IL-8 expression and EGF receptor-mediated MAPK activation in human colonocytes. However, the detailed signaling pathways involved in these responses remain to be elucidated. We report here that NT/NTR1 coupling in human colonic epithelial NCM460 cells activates tyrosine phosphorylation of the insulin-like growth factor-1 receptor (IGF-1R) in a time- and dose-dependent manner. NT also rapidly induces Src tyrosine phosphorylation, whereas pretreatment of cells with the Src inhibitor PP2 before NT exposure decreases NT-induced IGF-1R phosphorylation. In addition, inhibition of IGF-1R activation by either its specific antagonist AG1024 or siRNA against IGF-1 significantly reduces NT-induced IL-8 expression and NF-κB-dependent reporter gene expression. Pretreatment with AG1024 also inhibits Akt activation and apoptosis induced by NT. Silencing of Akt expression by siRNA also substantially attenuates NT-induced IL-8 promoter activity and NF-κB-dependent reporter gene expression. This is the first report to indicate that NT transactivates IGF-1R and that this response is linked to Akt phosphorylation and NF-κB activation, contributing to both pro-inflammatory and tissue repair signaling pathways in response to NT in colonic epithelial cells. We propose that IGF-1R activation represents a previously unrecognized key pathway involved in the mechanisms by which NT and NTR1 modulate colonic inflammation and inflammatory bowel disease.     

Influence of exercise training on resting blood pressures of Dahl rats

To determine whether female Dahl salt-sensitive (SS) hypertensive rats would adapt to chronic treadmill exercise by exhibiting lower resting systolic blood pressures (RSBP), a 12-wk training program was undertaken. Female Dahl salt-resistant (SR) rats were also trained for the same time period a a similar intensity [40-70% maximal O2 consumption (VO2max)] and duration (55 min). Postexperimental treadmill run times and VO2max values [SR: nontrained (NT) 87 +/- 1, trained (T) 97 +/- 2; SS: NT 82 +/- 2, T 92 +/- 3 ml.min-1 X min-1 X kg-1] indicated that the prescribed program had produced a trained state. However, the training program caused no group differences between the SR or the SS and their nontrained controls in measurements associated with sodium chloride intake, fluid consumption, urine production, 24-h sodium excretion, plasma volumes, plasma insulin, or blood volumes. Chronic exercise did significantly lower RSBP in the SR subgroup after 6 wk (NT 123 +/- 4, T 110 +/- 3 mmHg) and 8 wk (NT 120 +/- 4, T 106 +/- 2 mmHg) and remained lower throughout the remaining weeks of the experiment. On the other hand, the RSBP results of the trained SS rats were significantly higher than the nontrained SS rats after 6 wk (NT 155 +/- 8, T 191 +/- 7 mmHg) and were never significantly different than the controls for the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute embryonic exposure to corticosterone alters physiology,behaviour and growth in nestlings of a wild passerine

Maternally-derived glucocorticoids can modify the normal development of young animals. To date, little is known about maternal effects that are mediated by acute embryonic exposure to glucocorticoids. In birds, elevated maternal transmission of corticosterone (CORT) to egg albumen is mainly dependent on acute stress. In this study, we increased CORT levels in the egg albumen of a wild passerine, the great tit (Parus major), breeding in favourable deciduous and less suitable coniferous habitat. Subsequently we measured the somatic growth, baseline and acute glucocorticoid responses, immunity and behaviour of prenatally manipulated offspring with respect to control siblings. We found that prenatally CORT-exposed nestlings had lower baseline CORT levels, a more rapid decline in CORT during recovery from a standardized stressor, and a reduced heterophil/lymphocyte ratio compared with controls. Although stress-induced total CORT levels remained unchanged, free CORT levels were significantly lower and the levels of corticosteroid binding globulins (CBG) significantly higher in experimental offspring. Prenatally CORT-exposed offspring begged longer after hatching than controls. Stress-induced behavioural activity of fledglings did not differ between treatments, while its association with baseline CORT levels was significant in the control group only. The body mass and tarsus length of fledglings was positively affected by manipulation in unfavourable coniferous habitat only. We conclude that maternal effects related to elevated levels of albumen CORT modify diverse aspects of offspring phenotype and potentially increase offspring performance in resource poor environments. Moreover, our results indicate that maternal glucocorticoids may suppress the effect of hormones on behavioural responses.     

Effect of rocker shoe radius on oxygen consumption rate in young able-bodied persons

We studied oxygen consumption rate of eleven young able-bodied persons walking at self-selected speed with five different pairs of shoes: one regular pair without rocker soles (REG) and four pairs with uniform hardness (35-40 shore A durometer) rocker soles of different radii (25% of leg length (LL) (R25), 40% LL (R40), 55% LL (R55), and infinite radius (FLAT)). Rocker soled shoes in the study were developed to provide similar vertical lift (three inches higher than the REG shoes condition). Oxygen consumption rate was significantly affected by the use of the different shoes (p<0.001) and pairwise comparisons indicated that persons consumed significantly less oxygen (per minute per kilogram of body mass) when walking on the R40 shoes when compared with both the FLAT (p<0.001) and REG (p=0.021) shoe conditions. Oxygen consumption was also significantly less for the R25 shoes compared with the FLAT shoes (p=0.005) and for the R55 shoes compared with FLAT shoes (p=0.027). The three-inch lift on the FLAT shoe did not cause a significant change in oxygen consumption compared to the shoe without the lift (REG).