Lateralized effects of medial prefrontal cortex lesions on neuroendocrine and autonomic stress responses in rats. (17/9717)

The medial prefrontal cortex (mPFC) is highly activated by stress and modulates neuroendocrine and autonomic function. Dopaminergic inputs to mPFC facilitate coping ability and demonstrate considerable hemispheric functional lateralization. The present study investigated the potentially lateralized regulation of stress responses at the level of mPFC output neurons, using ibotenic acid lesions. Neuroendocrine function was assessed by plasma corticosterone increases in response to acute or repeated 20 min restraint stress. The primary index of autonomic activation was gastric ulcer development during a separate cold restraint stress. Restraint-induced defecation was also monitored. Plasma corticosterone levels were markedly lower in response to repeated versus acute restraint stress. In acutely restrained animals, right or bilateral, but not left mPFC lesions, decreased prestress corticosterone levels, whereas in repeatedly restrained rats, the same lesions significantly reduced the peak stress-induced corticosterone response. Stress ulcer development (after a single cold restraint stress) was greatly reduced by either right or bilateral mPFC lesions but was unaffected by left lesions. Restraint-induced defecation was elevated in animals with left mPFC lesions. Finally, a left-biased asymmetry in adrenal gland weights was observed across animals, which was unaffected by mPFC lesions. The results suggest that mPFC output neurons demonstrate an intrinsic right brain specialization in both neuroendocrine and autonomic activation. Such findings may be particularly relevant to clinical depression which is associated with both disturbances in stress regulatory systems and hemispheric imbalances in prefrontal function.  (+info)

A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. (18/9717)

Proteins modified by multiubiquitin chains are the preferred substrates of the proteasome. Ubiquitination involves a ubiquitin-activating enzyme, E1, a ubiquitin-conjugating enzyme, E2, and often a substrate-specific ubiquitin-protein ligase, E3. Here we show that efficient multiubiquitination needed for proteasomal targeting of a model substrate requires an additional conjugation factor, named E4. This protein, previously known as UFD2 in yeast, binds to the ubiquitin moieties of preformed conjugates and catalyzes ubiquitin chain assembly in conjunction with E1, E2, and E3. Intriguingly, E4 defines a novel protein family that includes two human members and the regulatory protein NOSA from Dictyostelium required for fruiting body development. In yeast, E4 activity is linked to cell survival under stress conditions, indicating that eukaryotes utilize E4-dependent proteolysis pathways for multiple cellular functions.  (+info)

Longevity, stress response, and cancer in aging telomerase-deficient mice. (19/9717)

Telomere maintenance is thought to play a role in signaling cellular senescence; however, a link with organismal aging processes has not been established. The telomerase null mouse provides an opportunity to understand the effects associated with critical telomere shortening at the organismal level. We studied a variety of physiological processes in an aging cohort of mTR-/- mice. Loss of telomere function did not elicit a full spectrum of classical pathophysiological symptoms of aging. However, age-dependent telomere shortening and accompanying genetic instability were associated with shortened life span as well as a reduced capacity to respond to stresses such as wound healing and hematopoietic ablation. In addition, we found an increased incidence of spontaneous malignancies. These findings demonstrate a critical role for telomere length in the overall fitness, reserve, and well being of the aging organism.  (+info)

Adrenosympathetic overactivity under conditions of work stress. (20/9717)

Serial measurements of urinary adrenaline, noradrenaline, and 11-hydroxycorticosteroid excretion were performed on 32 healthy men under two conditions of work stress; piecework and work on assembly line. A statistically significant increase in adrenaline, noradrenaline, and 11-hydroxycorticosteroids was observed for piecework and assembly line workers compared with salaried and 'ordinary' workers. The results support the assumption that psychosocial factors of an everyday type have significant effects on the sympathoadrenomedullary and adrenocortical function.  (+info)

Morphological adaptation to thermal stress in a marine fish, Fundulus heteroclitus. (21/9717)

Populations of Fundulus heteroclitus (Cyprinodontidae), a coastal marine fish, were studied in control and artificially heated environments on the north shore of Long Island to determine patterns of variation in morphology and the extent to which this variation reflected adaptation to environmental characteristics. Principal components and discriminant function analyses were used to analyze variation in and among seventeen morphological characters. Fishes living in water artificially heated by a power plant exhibited marked divergence from control populations in head morphology, and convergence with a population sampled at more southern latitudes. Hence, these differences were interpreted as adaptations to warm environments. Greater morphological variation is detected at the heated locality than at control localities, and this may be partially due to a breakdown in developmental homeostasis, and partially due to selection favoring phenotypes that are rare in this environment.  (+info)

Systemic hormonal, electrolyte, and substrate changes after non-thermal limb injury in children. (22/9717)

Relatively little is known regarding the hormonal changes after injury in children. Adult protocols are often applied to children, although the latter often have different physiological responses to trauma. Twenty children with an angulated displaced fracture of the radius and/or ulna (injury severity score 9) were studied prospectively for changes in adrenaline, noradrenaline, cortisol, angiotensin II, arginine vasopressin, urea, electrolytes, and glucose. Two blood samples were taken: one an arrival at the accident and emergency department and one preoperatively several hours later. There were marked increases in adrenaline, noradrenaline, cortisol, and arginine vasopressin above the normal range. Five (25%) cases demonstrated greater early increases in adrenaline than those reported for adult injuries of similar severity. Early hypokalaemia in four cases had corrected towards normal within a few hours, without potassium supplementation.  (+info)

Influence of bioenergetic stress on heat shock protein gene expression in nucleated red blood cells of fish. (23/9717)

The physiological and biochemical signals that induce stress protein (HSP) synthesis remain conjectural. In this study, we used the nucleated red blood cells from rainbow trout, Oncorhynchus mykiss, to address the interaction between energy status and HSP gene expression. Heat shock (25 degrees C) did not significantly affect ATP levels but resulted in an increase in HSP70 mRNA. Hypoxia alone did not induce HSP transcription in these cells despite a significant depression in ATP. Inhibition of oxidative phosphorylation with azide, in the absence of thermal stress, decreased ATP by 56% and increased lactate production by 62% but did not induce HSP gene transcription. Inhibition of oxidative phosphorylation and glycolysis with azide and iodoacetic acid respectively, decreased ATP by 79% and prevented lactate production, but did not induce either HSP70 or HSP30 gene transcription in these cells. This study demonstrates that a reduction in the cellular energy status will not induce stress protein gene transcription in rainbow trout red blood cells and may, in fact, limit induction during extreme metabolic inhibition.  (+info)

How dolphins use their blubber to avoid heat stress during encounters with warm water. (24/9717)

Dolphins have been observed swimming in inshore tropical waters as warm as 36-38 degrees C. A simple protocol that mimicked the thermal conditions encountered by a dolphin moving from cool pelagic to warm inshore water was used to determine how dolphins avoid hyperthermia in water temperatures (Tw) at and above their normal core temperature (Tc). Tw (2 sites), rectal temperature (Tre; 3 depths), and skin temperature (Tsk; 7 sites) and rate of heat flow (4-5 sites) between the skin and the environment were measured while the dolphin rested in a chamber during a 30-min baseline and 40-60 min while water was warmed at approximately 0.43 degrees C/min until temperatures of 34-36 degrees C were attained. Instead of the expected increase, Tre consistently showed declines during the warming ramp, sometimes by amounts that were remarkable both in their magnitude (1.35 degrees C) and rapidity (8-15 min). The reduction in Tre occurred even while heat loss to the environment was prevented by continued controlled warming of the water that kept Tw slightly above Tsk and while metabolic heat production alone should have added 1.6-2 degrees C/h to the Tc. This reduction in Tc could only be due to a massive redistribution of heat from the core to the blubber layer.  (+info)