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Biomedical subjects

M E Rice

Publications and source records attributed to M E Rice.

At least 19 recordsLinked to original sources
PubMed2002

Brain antioxidant regulation in mammals and anoxia-tolerant reptiles: balanced for neuroprotection and neuromodulation.

Reactive oxygen species (ROS) generated by mitochondrial respiration and other processes are often viewed as hazardous substances. Indeed, oxidative stress, defined as an imbalance between oxidant production and antioxidant protection, has been linked to several neurological disorders, including cerebral ischemia-reperfusion and Parkinson's disease. Consequently, cells and organisms have evolved specialized antioxidant defenses to balance ROS production and prevent oxidative damage. Research in our laboratory has shown that neuronal levels of ascorbate, a low molecular weight antioxidant, are ten-fold higher than those in much less metabolically active glial cells. Ascorbate levels are also selectively elevated in the CNS of anoxia-tolerant reptiles compared to mammals; moreover, plasma and CSF ascorbate concentrations increase markedly in cold-adapted turtles and in hibernating squirrels. Levels of the related antioxidant, glutathione, vary much less between neurons and glia or among species. An added dimension to the role of the antioxidant network comes from recent evidence that ROS can act as neuromodulators. One example is modulation of dopamine release by endogenous hydrogen peroxide, which we describe here for several mammalian species. Together, these data indicate adaptations that prevent oxidative stress and suggest a particularly important role for ascorbate. Moreover, they show that the antioxidant network must be balanced precisely to provide functional levels of ROS, as well as neuroprotection.

Animals↗
PubMed2002

Role of the antioxidant ascorbate in hibernation and warming from hibernation.

Ground squirrels tolerate up to 90% reductions in cerebral blood flow during hibernation as well as rapid reperfusion upon periodic arousal from torpor without apparent neurological damage. Thus, hibernation is studied as a model of tolerance to cerebral ischemia and other types of brain injury. Metabolic suppression likely plays a primary adaptive role that allows hibernating species to tolerate dramatic fluctuations in blood flow. Several other aspects of hibernation physiology are also consistent with tolerance to ischemia and reperfusion suggesting that multiple neuroprotective adaptations may work in concert during hibernation. The purpose of the present work is to review evidence for enhanced antioxidant defense systems during hibernation, with a focus on ascorbate, and discuss potential roles of these antioxidants during hibernation. In concert with dramatic decreases in blood flow, nutrient and oxygen delivery, plasma concentrations of the antioxidant ascorbate [(Asc)p] increase 3-5-fold during hibernation. In contrast, during re-warming, [Asc]p declines at a relatively rapid rate that peaks at the time of maximal O(2) consumption. This peak in O(2) consumption also coincides with a brief rise in plasma urate concentration consistent with a surge in reactive oxygen species production. Overall, data suggest that elevated concentration of plasma ascorbate is poised for distribution to metabolically active tissues during the surge in oxidative metabolism that accompanies re-warming during hibernation. This pool of ascorbate, as well as increased expression of other antioxidant defense systems, may protect vulnerable tissues from oxidative stress during hibernation and re-warming from hibernation. Better understanding of the role of ascorbate in hibernation may guide use of ascorbate and other antioxidants in treatment of stroke, head trauma and neurodegenerative disease.

Animals↗
PubMed2001

Novel Ca2+ dependence and time course of somatodendritic dopamine release: substantia nigra versus striatum.

Somatodendritic release of dopamine (DA) in midbrain represents a novel form of intercellular signaling that inherently differs from classic axon-terminal release. Here we report marked differences in the Ca(2+) dependence and time course of stimulated increases in extracellular DA concentration ([DA](o)) between the substantia nigra pars compacta (SNc) and striatum. Evoked [DA](o) was monitored with carbon-fiber microelectrodes and fast-scan cyclic voltammetry in brain slices. In striatum, pulse-train stimulation (10 Hz, 30 pulses) failed to evoke detectable [DA](o) in 0 or 0.5 mm Ca(2+) but elicited robust release in 1.5 mm Ca(2+). Release increased progressively in 2.0 and 2.4 mm Ca(2+). In sharp contrast, evoked [DA](o) in SNc was nearly half-maximal in 0 mm Ca(2+) and increased significantly in 0.5 mm Ca(2+). Surprisingly, somatodendritic release was maximal in 1.5 mm Ca(2+), with no change in 2.0 or 2.4 mm Ca(2+). Additionally, after single-pulse stimulation, evoked [DA](o) in striatum reached a maximum (t(max)) in <200 msec, whereas in SNc, [DA](o) continued to rise for 2-3 sec. Similarly, the time for [DA](o) to decay to 50% of maximum (t(50)) was 12-fold longer in SNc than striatum. A delayed t(max) in SNc compared with striatum persisted when DA uptake was inhibited by GBR-12909 and D(2) autoreceptors were blocked by sulpiride, although these agents eliminated the difference in t(50). Together, these data implicate different release mechanisms in striatum and SNc, with minimal Ca(2+) required to trigger prolonged DA release in SNc. Coupled with limited uptake, prolonged somatodendritic release would facilitate DA-mediated volume transmission in midbrain.

Animals↗
PubMed2001

Neuroprotective adaptations in hibernation: therapeutic implications for ischemia-reperfusion, traumatic brain injury and neurodegenerative diseases.

Brains of hibernating mammals are protected against a variety of insults that are detrimental to humans and other nonhibernating species. Such protection is associated with a number of physiological adaptations including hypothermia, increased antioxidant defense, metabolic arrest, leukocytopenia, immunosuppression, and hypocoagulation. It is intriguing that similar manipulations provide considerable protection as experimental treatments for central nervous system injury. This review focuses on neuroprotective mechanisms employed during hibernation that may offer novel approaches in the treatment of stroke, traumatic brain injury, and neurodegenerative diseases in humans.

Adaptation, Physiological↗
PubMed2001

HEPES prevents edema in rat brain slices.

Brain slices gain water when maintained in bicarbonate-buffered artificial cerebro-spinal fluid (ACSF) at 35 degrees C. We previously showed that this edema is linked to glutamate receptor activation and oxidative stress. An additional factor that may contribute to swelling is acidosis, which arises from high CO2 tension in brain slices. To examine the role of acidosis in slice edema, we added N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) to osmotically balanced ACSF (HEPES-ACSF), thereby increasing buffering capacity beyond that provided by bicarbonate/CO2. Water gain was markedly inhibited in HEPES-ACSF. After 3 h incubation in HEPES-ACSF at 35 degrees C, water gain was limited to that of fresh slices after 1 h recovery in ACSF at room temperature. The effect of HEPES in decreasing slice water gain was concentration dependent from 0.3 to 20 mM. The inhibition of water gain by HEPES suggests that tissue acidosis is a contributing factor in brain slice edema.

Acidosis↗
PubMed2001

Ascorbate dynamics and oxygen consumption during arousal from hibernation in Arctic ground squirrels.

During hibernation in Arctic ground squirrels (Spermophilus parryii), O(2) consumption and plasma leukocyte counts decrease by >90%, whereas plasma concentrations of the antioxidant ascorbate increase fourfold. During rewarming, O(2) consumption increases profoundly and plasma ascorbate and leukocyte counts return to normal. Here we investigated the dynamic interrelationships among these changes. Plasma ascorbate and uric acid (urate) concentrations were determined by HPLC from blood samples collected at approximately 15-min intervals via arterial catheter; leukocyte count and hematocrit were also determined. Body temperature, O(2) consumption, and electromyographic activity were recorded continuously. Ascorbate, urate, and glutathione contents in body and brain samples were determined during hibernation and after arousal. During rewarming, the maximum rate of plasma ascorbate decrease occurred at the time of peak O(2) consumption and peak plasma urate production. The ascorbate decrease did not correlate with mouth or abdominal temperature; uptake into leukocytes could account for only a small percentage. By contrast, liver and spleen ascorbate levels increased significantly after arousal, which could more than account for ascorbate clearance from plasma. Brain ascorbate levels remained constant. These data suggest that elevated concentrations of ascorbate [(Asc)] in plasma [(Asc)(p)] provide an antioxidant source that is redistributed to tissues during the metabolic stress that accompanies arousal.

Adipose Tissue↗
PubMed2001

Dopamine-mediated volume transmission in midbrain is regulated by distinct extracellular geometry and uptake.

Somatodendritic release of dopamine (DA) in midbrain is, at least in part, nonsynaptic; moreover, midbrain DA receptors are predominantly extrasynaptic. Thus somatodendritic DA mediates volume transmission, with an efficacy regulated by the diffusion and uptake characteristics of the local extracellular microenvironment. Here, we quantitatively evaluated diffusion and uptake in substantia nigra pars compacta (SNc) and reticulata (SNr), ventral tegmental area (VTA), and cerebral cortex in guinea pig brain slices. The geometric parameters that govern diffusion, extracellular volume fraction (alpha) and tortuosity (lambda), together with linear uptake (k'), were determined for tetramethylammonium (TMA(+)), and for DA, using point-source diffusion combined with ion-selective and carbon-fiber microelectrodes. TMA(+)-diffusion measurements revealed a large alpha of 30% in SNc, SNr, and VTA, which was significantly higher than the 22% in cortex. Values for lambda and k' for TMA(+) were similar among regions. Point-source DA-diffusion curves fitted theory well with linear uptake, with significantly higher values of k' for DA in SNc and VTA (0.08--0.09 s(-1)) than in SNr (0.006 s(-1)), where DA processes are sparser. Inhibition of DA uptake by GBR-12909 caused a greater decrease in k' in SNc than in VTA. In addition, DA uptake was slightly decreased by the norepinephrine transport inhibitor, desipramine in both regions, although this was statistically significant only in VTA. We used these data to model the radius of influence of DA in midbrain. Simulated release from a 20-vesicle point source produced DA concentrations sufficient for receptor activation up to 20 microm away with a DA half-life at this distance of several hundred milliseconds. Most importantly, this model showed that diffusion rather than uptake was the most important determinant of DA time course in midbrain, which contrasts strikingly with the striatum where uptake dominates. The issues considered here, while specific for DA in midbrain, illustrate fundamental biophysical properties relevant for all extracellular communication.

Animals↗
PubMed2001

H(2)O(2) is a novel, endogenous modulator of synaptic dopamine release.

Recent evidence suggests that reactive oxygen species (ROS) might act as modulators of neuronal processes, including synaptic transmission. Here we report that synaptic dopamine (DA) release can be modulated by an endogenous ROS, H(2)O(2). Electrically stimulated DA release was monitored in guinea pig striatal slices using carbon-fiber microelectrodes with fast-scan cyclic voltammetry. Exogenously applied H(2)O(2) reversibly inhibited evoked release in the presence of 1.5 mM Ca(2+). The effectiveness of exogenous H(2)O(2), however, was abolished or decreased by conditions that enhance Ca(2+) entry, including increased extracellular Ca(2+) concentration ([Ca(2+)](o); to 2.4 mM), brief, high-frequency stimulation, and blockade of inhibitory D(2) autoreceptors. To test whether DA release could be modulated by endogenous H(2)O(2), release was evoked in the presence of the H(2)O(2)-scavenging enzyme, catalase. In the presence of catalase, evoked [DA](o) was 60% higher than after catalase washout, demonstrating that endogenously generated H(2)O(2) can also inhibit DA release. Importantly, the Ca(2+) dependence of the catalase-mediated effect was opposite to that of H(2)O(2): catalase had a greater enhancing effect in 2.4 mM Ca(2+) than in 1.5 mM, consistent with enhanced H(2)O(2) generation in higher [Ca(2+)](o). Together these data suggest that H(2)O(2) production is Ca(2+) dependent and that the inhibitory mechanism can be saturated, thus preventing further effects from exogenous H(2)O(2). These findings show for the first time that endogenous H(2)O(2) can modulate vesicular neurotransmitter release, thus revealing an important new signaling role for ROS in synaptic transmission.

Animals↗
PubMed2001

Effect of planting dates and Bacillus thuringiensis corn on the population dynamics of European corn borer (Lepidoptera: Crambidae).

Field studies were conducted to determine how field corn, Zea mays L., phenologies in combination with transgenic Bacillus thuringiensis Berliner (Bt) corn and non-Bt (near isogenic) corn could affect egg laying by female European corn borer, Ostrinia nubilalis (Hubner), and subsequent larval injury. Transgenic Bt (events 176 and Bt11) and non-Bt corn was planted at three different times to assess the use of early- and late- planted Bt corn as a means for egg recruitment to these targeted planting dates. Plant growth stages, egg densities, and stalk tunneling was recorded at four locations in southwestern, central, and northern Iowa for three summers (1996-1998). No significant differences in egg densities were observed between Bt and non-Bt corn during the first and second generation for all three years. Significant differences did occur among planting dates. Between 50 and 100% of the eggs were laid in the early planting during the first generation. In addition, between 40 and 65% of the eggs were laid in the late planting for the second generation. Correlations between egg density and larval tunneling were inconsistent from year to year. Additional inconsistencies stemming from yearly phenological differences among sequential plantings and variable O. nubilalis populations increases the difficulty in recommending planting date adjustments as a practical management tool for European corn borer and Bt corn.

Agriculture↗
PubMed2000

Mechanisms underlying H(2)O(2)-mediated inhibition of synaptic transmission in rat hippocampal slices.

Hydrogen peroxide (H(2)O(2)) inhibits the population spike (PS) evoked by Schaffer collateral stimulation in hippocampal slices. Proposed mechanisms underlying this effect include generation of hydroxyl radicals (.OH) and inhibition of presynaptic Ca(2+) entry. We have examined these possible mechanisms in rat hippocampal slices. Inhibition of the evoked PS by H(2)O(2) was sharply concentration-dependent: 1.2 mM H(2)O(2) had no effect, whereas 1.5 and 2.0 mM H(2)O(2) reversibly depressed PS amplitude by roughly 80%. The iron chelator, deferoxamine (1 mM), and the endogenous.OH scavenger, ascorbate (400 microM), prevented PS inhibition, confirming.OH involvement. Isoascorbate (400 microM), which unlike ascorbate is not taken up by brain cells, also prevented PS inhibition, indicating an extracellular site of.OH generation or action. We then investigated whether H(2)O(2)-induced PS depression could be overcome by prolonged stimulation, which enhances Ca(2+) entry. During 5-s, 10-Hz trains under control conditions, PS amplitude increased to over 200% during the first three-four pulses, then stabilized. In the presence of H(2)O(2), PS amplitude was initially depressed, but began to recover after 2.5 s of stimulation, finally reaching 80% of the control maximum. In companion experiments, we assessed the effect of H(2)O(2) on presynaptic Ca(2+) entry by monitoring extracellular Ca(2+) concentration ([Ca(2+)](o)) during train stimulation in the presence of postsynaptic receptor blockers. Evoked [Ca(2+)](o) shifts were apparently unaltered by H(2)O(2), suggesting a lack of effect on Ca(2+) entry. Taken together, these findings suggest new ways in which reactive oxygen species (ROS) might act as signaling agents, specifically as modulators of synaptic transmission.

Action Potentials↗
PubMed2000

Ascorbate regulation and its neuroprotective role in the brain.

Ascorbic acid (vitamin C) occurs physiologically as the ascorbate anion: a water-soluble antioxidant that is found throughout the body. However, despite the high, homeostatically regulated levels of brain ascorbate, its specific functions in the CNS are only beginning to be elucidated. Certainly, it acts as part of the intracellular antioxidant network, and as such is normally neuroprotective. There is also evidence that it acts as a neuromodulator. A possibly unique role it might have is as an antioxidant in the brain extracellular microenvironment, where its concentration is modulated by glutamate-ascorbate heteroexchange at glutamate uptake sites. Ongoing studies of ascorbate and glutamate transporters should lead to rapid progress in understanding ascorbate regulation and function.

Animals↗
PubMed2000

The functions of aggression by male teenagers.

A selectionist theory states that violence by males toward male peers originally served specific functions and violence to female peers served others. Differences in self-reported victimization and perpetration in studies of 1.452 high school students were hypothesized. In Study 1, male-to-male aggression was reported to be more prevalent than male-to-female aggression. For male-to-male aggression, perpetrator reports agreed with or exceeded victim reports, and victims were more often strangers than close friends, In contrast, for male-to-female aggression, there were consistently fewer reports from perpetrators than from victims, and victims were less often strangers than girlfriends. Study 2 obtained similar findings for reported frequency, number of victims and perpetrators, and sexual aggression. Study 3 showed that girls' aggression contrasted with that by boys with respect to intra- versus intersex aggression and perpetrator victim agreement.

Adolescent↗
PubMed2000

Ascorbate inhibits edema in brain slices.

Ascorbate is an essential antioxidant in the CNS, localized predominantly in neuronal cytosol. Slices of mammalian brain rapidly lose ascorbate, however, when incubated in ascorbate-free media; brain slices also take up water and swell. Here we investigated water gain in coronal slices of rat forebrain incubated with and without ascorbate for 1-3 h at 34 degrees C. Slices progressively gained water in ascorbate-free media, with a significant 12% water increase after 3 h at 34 degrees C, compared with the water content of slices after a 1-h recovery period at 24 degrees C, immediately following slice preparation. Inclusion of 400 micro M ascorbate in the medium led to an increase in tissue ascorbate content and prevented water gain at 34 degrees C. By contrast, water gain was not inhibited by isoascorbate or thiourea, which are antioxidants that are not accumulated in brain cells. The oxidant H2O2 enhanced water gain, whereas a cocktail of NMDA and non-NMDA receptor blockers inhibited edema formation to the same extent as ascorbate. These data demonstrate that brain edema, linked to glutamate-receptor activation, can result from intracellular oxidative stress and that this can be prevented by ascorbate.

Animals↗
PubMed1999

Ascorbate and glutathione regulation in hibernating ground squirrels.

Ground squirrels withstand up to 90% reductions in cerebral blood flow during hibernation as well as rapid reperfusion upon periodic arousals from torpor. Metabolic suppression likely plays a primary adaptive role which allows hibernating species to tolerate such phenomena. However, several other aspects of hibernation physiology are also consistent with tolerance to dramatic fluctuations in cerebral blood flow, suggesting that multiple neuroprotective adaptations may work in concert during hibernation. The purpose of the present work was to study the dynamics of the low molecular weight antioxidants, ascorbate and glutathione (GSH), during hibernation. Alterations in concentrations of ascorbate during hibernation and arousal in two species of hibernating ground squirrels suggest that it could play a protective role during hibernation or arousal. Samples were collected during the hibernation season from arctic ground squirrels (AGS; Spermophilus parryii) and 13-lined ground squirrels (TLS; S. tridecemlineatus) during prolonged torpor and in squirrels that did not hibernate or had not been hibernating for several weeks. We determined antioxidant levels in plasma, cerebrospinal fluid (CSF), and in frontal cortex, hippocampus and cerebellum using high-performance liquid chromatography (HPLC). Plasma ascorbate concentrations increased dramatically (3-4-fold) in both species during hibernation and rapidly returned to prehibernation levels upon arousal. By contrast, plasma GSH concentrations fell slightly or remained stable during hibernation. Ascorbate levels in the CSF doubled in hibernating AGS (not determined in TLS), while brain ascorbate content fell slightly (10-15%) in both species. Substantial increases in plasma and CSF ascorbate concentrations suggest that this antioxidant could play a protective role during hibernation and reperfusion upon arousal from hibernation.

Animals↗
PubMed1999

Birth order and fluctuating asymmetry: a first look.

We investigated the hypothesis that maternal immunoreactivity to male-specific features of the foetus can increase developmental instability. We predicted that the participants' number of older brothers would be positively related to the fluctuating asymmetry of ten bilateral morphological traits. The participants were 40 adult male psychiatric patients and 31 adult male hospital employees. Consistent with the hypothesis, the participants' number of older brothers--but not number of older sisters, younger brothers or younger sisters--was positively associated with fluctuating asymmetry. The patients had significantly larger fluctuating asymmetry scores and tended to have more older brothers than the employees, but the positive relationship between the number of older brothers and fluctuating asymmetry was observed in both groups.

Adult↗
PubMed1999

Use of ascorbate in the preparation and maintenance of brain slices.

Ascorbate and glutathione (GSH) are normally concentrated in brain cells at millimolar levels. However, both of these low-molecular-weight antioxidants are washed out of mammalian brain tissue during slice preparation and subsequent incubation. Ascorbate, which is not synthesized in the brain, can be added back to slices by active uptake from the incubation medium. Levels of GSH, on the other hand, are regulated by synthesis rather than uptake, and cannot be readily maintained in slices. Importantly, maintenance of brain slice ascorbate content at at least 50% of that in vivo, prevents the increase in slice water content that normally occurs during incubation. Slices with maintained ascorbate levels also have better histological characteristics than ascorbate-depleted tissue. The medium concentration of ascorbate sufficient to maintain content and inhibit edema formation is 400 microM, which is the normal concentration in brain extracellular fluid. This paper describes methods to maintain ascorbate levels in brain slices, including procedures to minimize oxidation in oxygenated incubation media. Also described is an HPLC analysis for ascorbate and GSH that is based on direct injection rather than extraction of samples.

Analysis of Variance↗
PubMed1999

Ascorbate compartmentalization in the CNS.

Ascorbic acid, found physiologically as the ascorbate anion, is an abundant water-soluble antioxidant. It is concentrated in the intracellular compartment of all tissues in the body. The CNS has particularly high levels of ascorbate. Recent data from this laboratory indicate that ascorbate is distinctly compartmentalized between neurons and glia, with an average intracellular concentration of 10 mM in neurons and 1 mM in glial cells. These data can be contrasted with those for another important low molecular weight antioxidant, glutathione, which is somewhat more concentrated in glia than in neurons. The present review summarizes evidence for ascorbate compartmentalization between neurons and glia and considers these data in light of evidence for the roles of ascorbate as a neuroprotective antioxidant and as a neuromodulator in the CNS.

Journal Article↗