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Clinical and experimental research has demonstrated that the emotional experience of fear and anxiety impairs postural stability in humans. The current study investigated whether changes in fear and anxiety can also modulate spinal stretch reflexes and the gain of afferent inputs to the primary somatosensory cortex. To do so, two separate experiments were performed on two separate groups of participants while they stood under conditions of low and high postural threat. In experiment 1, the proprioceptive system was probed using phasic mechanical stimulation of the Achilles tendon while simultaneously recording the ensuing tendon reflexes in the soleus muscle and cortical-evoked potentials over the somatosensory cortex during low and high threat conditions. In experiment 2, phasic electrical stimulation of the tibial nerve was used to examine the effect of postural threat on somatosensory evoked potentials. Results from experiment 1 demonstrated that soleus tendon reflex excitability was facilitated during states of height-induced fear and anxiety while the magnitude of the tendon-tap-evoked cortical potential was not significantly different between threat conditions. Results from experiment 2 demonstrated that the amplitudes of somatosensory-evoked potentials were also unchanged between threat conditions. The results support the hypothesis that muscle spindle sensitivity in the triceps surae muscles may be facilitated when humans stand under conditions of elevated postural threat, although the presumed increase in spindle sensitivity does not result in higher afferent feedback gain at the level of the somatosensory cortex.

Placental ischemia during pregnancy is thought to release cytokines such as tumor necrosis factor-alpha (TNF-alpha), which may contribute to the increased vascular resistance associated with pregnancy-induced hypertension. We have reported that a chronic twofold elevation in plasma TNF-alpha increases blood pressure in pregnant but not in virgin rats; however, the vascular mechanisms are unclear. We tested the hypothesis that increasing plasma TNF-alpha during pregnancy impairs endothelium-dependent vascular relaxation and enhances vascular reactivity. Active stress was measured in aortic strips of virgin and late-pregnant Sprague-Dawley rats untreated or infused with TNF-alpha (200 ng x kg(-1) x day(-1) for 5 days) to increase plasma level twofold. Phenylephrine (Phe) increased active stress to a maximum of 4.2 +/- 0.4 x 10(3) and 9.9 +/- 0.7 x 10(3) N/m2 in control pregnant and TNF-alpha-infused pregnant rats, respectively. Removal of the endothelium enhanced Phe-induced stress in control but not in TNF-alpha-infused pregnant rats. In endothelium-intact strips, ACh caused greater relaxation of Phe contraction in control than in TNF-alpha-infused pregnant rats. Basal and ACh-induced nitrite/nitrate production was less in TNF-alpha-infused than in control pregnant rats. Pretreatment of vascular strips with 100 microM N(G)-nitro-L-arginine methyl ester, to inhibit nitric oxide (NO) synthase, or 1 microM 1H-[1,2,4]oxadiazolo[4,3-]quinoxalin-1-one, to inhibit cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced stress in control but not in TNF-alpha-infused pregnant rats. Phe contraction and ACh relaxation were not significantly different between control and TNF-alpha-infused virgin rats. Thus an endothelium-dependent NO-cGMP-mediated vascular relaxation pathway is inhibited in late-pregnant rats infused with TNF-alpha. The results support a role for TNF-alpha as one possible mediator of the increased vascular resistance associated with pregnancy-induced hypertension.

Background: We investigated the effects of chronic ethanol exposure on physical development, reproduction, and life expectancy of Caenorhabditis elegans, a microscopic nematode worm. It has a small nervous system of 302 neurons and a short lifespan of 2 to 3 weeks.Methods: In this study, the worms were chronically exposed to varying concentrations of ethanol for different periods of their life: for their entire lifespan, during larval development only, and during adulthood only. In addition, the worms were exposed to ethanol acutely during different stages of embryonic development.Results: Chronic exposure to ethanol during larval development temporarily delayed physical growth, slowed development, delayed the onset of reproductive maturity, and decreased both reproductive fecundity and longevity. Chronic exposure to ethanol beginning when worms completed development and reached reproductive maturity resulted in reduced C. elegans body length, decreased reproductive fecundity, and life expectancy. Finally, acute embryonic exposure of C. elegans eggs to high concentrations of ethanol at different stages of development resulted in a lower probability of exposed eggs hatching into larval worms depending on when eggs were exposed during development. Furthermore, some of the worms that did hatch displayed distinct physical dysmorphologies as a consequence of acute ethanol exposure during embryonic development.Conclusions: These data suggest that exposing C. elegans to ethanol during critical development periods results in characteristic phenotypic outcomes. Thus, C. elegans offers a novel model for exploring the mechanisms by which ethanol exposure affects development.