University of Texas Medical Branch

About: University of Texas Medical Branch is a education organization based out in Galveston, Texas, United States. It is known for research contribution in the topics: Population & Virus. The organization has 22033 authors who have published 38268 publications receiving 1517502 citations. The organization is also known as: The University of Texas Medical Branch at Galveston & UTMB.

Cognitive Impairment in Pain through Amygdala-Driven Prefrontal Cortical Deactivation

Abstract: Cognitive deficits such as impaired decision-making can be a consequence of persistent pain. Normal functions of the intact amygdala and prefrontal cortex are required for emotion-based decision-making that relies on the ability to assess risk, attribute value, and identify advantageous strategies. We tested the hypothesis that pain-related cognitive deficits result from amygdala-driven impairment of medial prefrontal cortical (mPFC) function. To do this, we used electrophysiological single-unit recordings in vivo, patch clamp in brain slices, and various behavioral assays to show that increased neuronal activity in the amygdala in an animal model of arthritis pain was accompanied by decreased mPFC activation and impaired decision-making. Furthermore, pharmacologic inhibition (with a corticotropin-releasing factor 1 receptor antagonist) of pain-related hyperactivity in the basolateral amygdala (BLA), but not central amygdala (CeA), reversed deactivation of mPFC pyramidal cells and improved decision-making deficits. Pain-related cortical deactivation resulted from a shift of balance between inhibitory and excitatory synaptic transmission. Direct excitatory transmission to mPFC pyramidal cells did not change in the pain model, whereas polysynaptic inhibitory transmission increased. GABAergic transmission was reduced by non-NMDA receptor antagonists, suggesting that synaptic inhibition was glutamate driven. The results are consistent with a model of BLA-driven feedforward inhibition of mPFC neurons. In contrast to the differential effects of BLA versus CeA hyperactivity on cortical-cognitive functions, both amygdala nuclei modulate emotional-affective pain behavior. Thus, this study shows that the amygdala contributes not only to emotional-affective but also cognitive effects of pain. The novel amygdalo-cortical pain mechanism has important implications for our understanding of amygdala functions and amygdalo-cortical interactions.

Ryanodine receptor adaptation: control mechanism of Ca(2+)-induced Ca2+ release in heart

Abstract: Adaptation of single cardiac ryanodine receptor (RyR) channels was demonstrated by application of the caged calcium ion (Ca2+) methodology. In contrast to conventional desensitization found in surface membrane ligand-gated channels, single cardiac RyR channels adapted to maintained Ca2+ stimuli, preserving their ability to respond to a second (larger) Ca2+ stimulus. RyR adaptation may represent a molecular control mechanism for smoothly graded Ca(2+)-induced Ca2+ release in heart and may be a fundamental feature of channels, including the inositol triphosphate receptor, that are involved in intracellular Ca2+ signaling in many cell types.

Abnormal anxiety-related behavior in serotonin transporter null mutant mice: the influence of genetic background

Abstract: Serotonin transporter (5-HTT) null mutant mice provide a model system to study the role genetic variation in the 5-HTT plays in the regulation of emotion. Anxiety-like behaviors were assessed in 5-HTT null mutants with the mutation placed on either a B6 congenic or a 129S6 congenic background. Replicating previous findings, B6 congenic 5-HTT null mutants exhibited increased anxiety-like behavior and reduced exploratory locomotion on the light dark exploration and elevated plus-maze tests. In contrast, 129S6 congenic 5-HTT null mutant mice showed no phenotypic abnormalities on either test. 5-HTT null mutants on the 129S6 background showed reduced 5-HT(1A) receptor binding (as measured by quantitative autoradiography) and reduced 5-HT(1A) receptor function (as measured by 8-OH-DPAT-induced hypothermia). These data confirm that the 5-HTT null mutation produced alterations in brain 5-HT function in mice on the 129S6 background, thereby discounting the possibility that the absence of an abnormal anxiety-like phenotype in these mice was due to a suppression of the mutation by 129 modifier genes. Anxiety-like behaviors in the light dark exploration and elevated plus-maze tests were significantly higher in 129S6 congenic +/+ mice as compared to B6 congenic +/+ mice. This suggests that high baseline anxiety-like behavior in the 129S6 strain might have precluded detection of the anxiety-like effects of the 5-HTT null mutation on this background. Present findings provide further evidence linking genetic variation in the 5-HTT to abnormalities in mood and anxiety. Furthermore, these data highlight the utility of conducting behavioral phenotyping of mutant mice on multiple genetic backgrounds.

Gait and step training to reduce falls in Parkinson's disease

Abstract: Introduction: Frequent falls and risk of injury are evident in individuals with Parkinson's disease (PD) as the disease progresses. There have been no reports of any interventions that reduce the incidence of falls in idiopathic PD. Purpose: Assess the benefit of gait and step perturbation training in individuals with PD. Design: Randomized, controlled trial. Setting: Outpatient research, education and clinical center in a tertiary care Veterans Affairs Medical Center. Outcome measures: Gait parameters, 5-step test, report of falls Subjects: Eighteen men with idiopathic PD in stage 2 or 3 of the Hoehn and Yahr staging Methods: Subjects were randomly assigned to a trained or control group. They were asked about any falls 2 weeks prior to and after an 8 week period. Gait speed, cadence, and step length were tested on an instrumented walkway. Subjects were timed while stepping onto and back down from an 8.8 cm step for 5 consecutive steps. Gait training consisted of walking on a treadmill at a speed greater than over ground walking speed while walking in 4 directions and while supported in a harness for safety. Step training consisted of suddenly turning the treadmill on and off while the subject stood in the safety harness facing either forwards, backwards, or sideways. Training occurred 1 hour per day, three times per week for 8 weeks. A two-factor (time and group) analysis of variance with repeated measures was used to compare the groups. Results: Substantial reduction occurred in falls in the trained group, but not in the control group. Gait speed increased in the trained group from 1.28 ± 0.33 meters/sec to 1.45 ± 0.37 meters/sec, but not in the control group (from 1.26 to 1.27 m/s). The cadence increased for both groups: from 112.8 to 120.3 steps/min for the trained group and 117.7 to 124.3 steps/min for the control group. Stride lengths increased for the trained group, but not the control group. The 5-step test speed increased in the trained group from 0.40 ± 0.08 steps/sec to 0.51 ± 0.12 steps/sec, and in the control group (0.36 ± 0.11 steps/sec to 0.42 ± 0.11

The pathophysiology of disc degeneration A CRITICAL REVIEW

Abstract: The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries. This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors.