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Substrates Underlying (substrate + underlying)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Resveratrol: Preventing properties against vascular alterations and ageing

MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 5 2005
Dominique Delmas
Abstract Cardiovascular diseases are the leading cause of death in developed countries where the common pathological substrate underlying this process is atherosclerosis. Several new concepts have emerged in relation to mechanisms that contribute to the regulation of the vascular diseases and associated inflammatory effects. Recently, potential antioxidants (vitamin E, polyphenols) have received much attention as potential anti-atherosclerotic agents. Among the polyphenols with health benefic properties, resveratrol, a phytoalexin of grape, seem to be a good candidate protecting the vascular walls from oxidation, inflammation, platelet aggregation, and thrombus formation. In this review, we focus on the mechanism of resveratrol cardiovascular benefic effects. We analyze, in relation with the different steps of atherosclerotic process, the resveratrol properties at multiple levels, such as cellular signaling, enzymatic pathways, apoptosis, and gene expression. We show and discuss the relationship with reactive oxygen species, regulation of pro-inflammatory genes including cycloxygenases and cytokines in molecular inflammatory and aging processes, and how the regulation of these activites by resveratrol can lead to a prevention of vascular diseases. [source]

Platelet activation and secretion in patients with major depression, thoracic aortic atherosclerosis, or renal dialysis treatment

DEPRESSION AND ANXIETY, Issue 3 2002
Dominique L. Musselman M.D., M.S.
Abstract Relatively little is known concerning the magnitude of alterations of platelet activation and secretion markers of patients with major depression when compared to patients at increased risk for, or with current, clinically significant atherosclerosis. Markers of in vivo platelet stimulation and secretion were measured under basal conditions in normal comparison subjects (n = 12) and three patient groups: patients diagnosed with DSM-IV major depression (n = 15), dialysis-dependent patients (n = 12), and patients with severe thoracic aortic atherosclerosis (n = 10). In comparison to normal comparison subjects, depressed patients and patients with thoracic aortic atherosclerosis exhibited the greatest platelet stimulation as detected by increased anti-LIBS platelet binding. Dialysis-dependent patients exhibited the highest plasma concentrations of the renally-excreted platelet-specific secretion protein, ,-thromboglobulin. This study extends previous observations of increased platelet activation in patients with major depression and documents similar alterations in patients with transesophageal echocardiography (TEE)-documented thoracic aortic atherosclerosis. Future studies will determine whether the magnitude of platelet stimulation and secretion in patients with comorbid depression and atherosclerotic aortic disease is greater than that observed in nondepressed patients with atherosclerotic aortic disease or major depression alone. These findings provide further evidence for either increased platelet activation and/or intrinsic heightened platelet reactivity as one of the biological substrates underlying the increased risk of depressed patients for cardiovascular disease. Depression and Anxiety 15:91,101, 2002. © 2002 Wiley-Liss, Inc. [source]

Serotonin 5-HT2C receptors regulate anxiety-like behavior

GENES, BRAIN AND BEHAVIOR, Issue 5 2007
L. K. Heisler
Central serotonin (5-hydroxytryptamine, 5-HT) systems have been implicated in the pathophysiology and treatment of anxiety disorders, which are among the world's most prevalent psychiatric conditions. Here, we report that the 5-HT2C receptor (5-HT2CR) subtype is critically involved in regulating behaviors characteristic of anxiety using male 5-HT2CR knockout (KO) mice. Specific neural substrates underlying the 5-HT2CR KO anxiolytic phenotype were investigated, and we report that 5-HT2CR KO mice display a selective blunting of extended amygdala corticotropin-releasing hormone neuronal activation in response to anxiety stimuli. These findings illustrate a mechanism through which 5-HT2CRs affect anxiety-related behavior and provide insight into the neural circuitry mediating the complex psychological process of anxiety. [source]

Neural basis of first and second language processing of sentence-level linguistic prosody

HUMAN BRAIN MAPPING, Issue 2 2007
Jackson Gandour
Abstract A fundamental question in multilingualism is whether the neural substrates are shared or segregated for the two or more languages spoken by polyglots. This study employs functional MRI to investigate the neural substrates underlying the perception of two sentence-level prosodic phenomena that occur in both Mandarin Chinese (L1) and English (L2): sentence focus (sentence-initial vs. -final position of contrastive stress) and sentence type (declarative vs. interrogative modality). Late-onset, medium proficiency Chinese-English bilinguals were asked to selectively attend to either sentence focus or sentence type in paired three-word sentences in both L1 and L2 and make speeded-response discrimination judgments. L1 and L2 elicited highly overlapping activations in frontal, temporal, and parietal lobes. Furthermore, region of interest analyses revealed that for both languages the sentence focus task elicited a leftward asymmetry in the supramarginal gyrus; both tasks elicited a rightward asymmetry in the mid-portion of the middle frontal gyrus. A direct comparison between L1 and L2 did not show any difference in brain activation in the sentence type task. In the sentence focus task, however, greater activation for L2 than L1 occurred in the bilateral anterior insula and superior frontal sulcus. The sentence focus task also elicited a leftward asymmetry in the posterior middle temporal gyrus for L1 only. Differential activation patterns are attributed primarily to disparities between L1 and L2 in the phonetic manifestation of sentence focus. Such phonetic divergences lead to increased computational demands for processing L2. These findings support the view that L1 and L2 are mediated by a unitary neural system despite late age of acquisition, although additional neural resources may be required in task-specific circumstances for unequal bilinguals. Hum. Brain Mapp, 2007. © 2006 Wiley-Liss, Inc. [source]

Acute and Chronic Ethanol Modulate Dopamine D2-Subtype Receptor Responses in Ventral Tegmental Area GABA Neurons

ALCOHOLISM, Issue 5 2009
Kimberly H. Ludlow
Background:, Ventral tegmental area (VTA) ,-aminobutyric acid (GABA) neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in drug reward. VTA GABA neuron firing rate is reduced by acute ethanol and enhanced by DA via D2 receptor activation. The objective of this study was to evaluate the role of D2 receptors in acute ethanol inhibition of VTA GABA neuron activity, as well as the adaptation of D2 receptors by chronic ethanol consumption. Methods:, Using electrophysiological methods, we evaluated the effects of intraperitoneal ethanol on DA activation of VTA GABA neurons, the effects of DA antagonists on ethanol inhibition of their firing rate, as well as adaptations in firing rate following chronic ethanol consumption. Using single cell quantitative RT-polymerase chain reaction (PCR), we evaluated the expression of VTA GABA neuron D2 receptors in rats consuming ethanol versus pair-fed controls. Results:, In acute ethanol studies, microelectrophoretic activation of VTA GABA neurons by DA was inhibited by acute intraperitoneal ethanol, and intravenous administration of the D2 antagonist eticlopride blocked ethanol suppression of VTA GABA neuron firing rate. In chronic ethanol studies, while there were no signs of withdrawal at 24 hours, or significant adaptation in firing rate or response to acute ethanol, there was a significant down-regulation in the expression of D2 receptors in ethanol-consuming rats versus pair-fed controls. Conclusions:, Inhibition of DA activation of VTA GABA neuron firing rate by ethanol, as well as eticlopride block of ethanol inhibition of VTA GABA neuron firing rate, suggests an interaction between ethanol and DA neurotransmission via D2 receptors, perhaps via enhanced DA release in the VTA subsequent to ethanol inhibition of GABA neurons. Down-regulation of VTA GABA neuron D2 receptors by chronic ethanol might result from persistent DA release onto GABA neurons. [source]

Prenatal Alcohol Exposure Affects Frontal,Striatal BOLD Response During Inhibitory Control

ALCOHOLISM, Issue 8 2007
Susanna L. Fryer
Background: Prenatal alcohol exposure can lead to widespread cognitive impairment and behavioral dysregulation, including deficits in attention and response inhibition. This study characterized the neural substrates underlying the disinhibited behavioral profile of individuals with fetal alcohol spectrum disorders (FASD). Methods: Children and adolescents (ages 8,18) with (n=13) and without (n=9) histories of heavy prenatal alcohol exposure underwent functional magnetic resonance imaging while performing a response inhibition (go/no-go) task. Results: Despite similar task performance (mean response latency, performance accuracy, and signal detection), blood oxygen level-dependent (BOLD) response patterns differed by group. Region-of-interest analyses revealed that during portions of the behavioral task that required response inhibition, alcohol-exposed participants showed greater BOLD response across prefrontal cortical regions (including the left medial and right middle frontal gyri), while they showed less right caudate nucleus activation, compared with control participants. Conclusions: These data provide an account of response inhibition-related brain functioning in youth with FASD. Furthermore, results suggest that the frontal,striatal circuitry thought to mediate inhibitory control is sensitive to alcohol teratogenesis. [source]