Biomedical subjects

B Shukitt-Hale

Publications and source records attributed to B Shukitt-Hale.

At least 19 recordsLinked to original sources

PubMed2006

Relative effectiveness of different particles and energies in disrupting behavioral performance.

On exploratory class missions to other planets, astronauts will be exposed to varieties and doses of heavy particles, which are not experienced in low earth orbit. These particles can affect neurobehavioral function and potentially interfere with the ability of astronauts to successfully meet mission requirements. While a significant amount of research has been performed on the relative biological effectiveness (RBE) of different types of heavy particles on cytogenetic function, little research has been done on the effectiveness of different particles on central nervous system function and on cognitive/behavioral performance. The present paper reviews some recent research on the effects of exposure to different types and energies of heavy particles on the performance of two behavioral tasks which depend upon the integrity of the central dopaminergic system. This review indicates that the RBE of different particles for neurobehavioral dysfunction cannot be predicted only on the basis of the linear energy transfer of the specific particle.

Animals↗

PubMed2005

The effects of antioxidants in the senescent auditory cortex.

We investigated whether a 2-month dietary supplementation of antioxidants, in the form of blueberry phytochemicals, could reverse or retard the age-related decline in temporal processing speed observed in the aged rat. To this end, extracellular single unit responses to frequency modulated (FM) sweeps were recorded in the primary auditory cortex (AI) of aged rats that had been placed on either a blueberry-supplemented or control diet 2 months prior to the physiological recordings. Results showed that most cells recorded from the blueberry-fed rats responded most vigorously to fast FM sweeps, similar to that observed in young rats. In contrast, the majority of cells recorded from the control rats showed a preference for slow FM sweep rates. These results suggest that age-related changes in temporal processing speed in A1 may be reversed by dietary supplementation of blueberry phytochemicals.

Action Potentials↗

PubMed2004

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function.

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.

Amphetamine↗

PubMed2004

The effects of proton exposure on neurochemistry and behavior.

Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, alpha particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints.

Animals↗

PubMed2004

The effects of heavy particle irradiation on exploration and response to environmental change.

Free radicals produced by exposure to heavy particles have been found to produce motor and cognitive behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability of male Sprague-Dawley rats to detect novel arrangements in a given environment. Using a test of spatial memory previously demonstrated to be sensitive to aging, open field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy (n=10) of 56Fe heavy particle radiation or in non-radiated controls (n=10). Animals irradiated with 1.5 Gy of 56Fe particles exhibited some age-like effects in rats tested, even though they were, for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open field, independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects spend significantly more time exploring novel objects placed in the open field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open field exploratory behavior, but did not elicit age-like effects during the spatial and non-spatial rearrangement tasks.

Aging↗

PubMed2003

Cognitive deficits induced by 56Fe radiation exposure.

Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

Aging↗

PubMed2003

Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle.

Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0 Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning.

Adjuvants, Immunologic↗

PubMed2003

Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model.

Previously, we showed that blueberry (BB) supplementation reversed the deleterious effects of aging on motor behavior and neuronal signaling in senescent rodents. We now report that BB-fed (from 4 months of age) APP + PS1 transgenic mice showed no deficits in Y-maze performance (at 12 months of age) with no alterations in amyloid beta burden. It appeared that the protective mechanisms are derived from BB-induced enhancement of memory-associated neuronal signaling (e.g. extracellular signal-regulated kinase) and alterations in neutral sphingomyelin-specific phospholipase C activity. Thus, our data indicate for the first time that it may be possible to overcome genetic predispositions to Alzheimer disease through diet.

Alzheimer Disease↗

PubMed2002

Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation.

Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior.

Animals↗

PubMed2001

Tyrosine improves behavioral and neurochemical deficits caused by cold exposure.

The effects of acute cold stress were assessed behaviorally and neurochemically. The norepinephrine (NE) precursor, tyrosine (TYR), the catecholamine-releasing compound, amphetamine (AMPH), and the adrenoceptor agonist, phenylpropanolamine (PPA), were administered systemically either alone or in conjunction with TYR 30 min prior to cold exposure. All three sympathomimetic treatments dose-dependently improved performance in a forced swim test following hypothermia (T(c)=30 degrees C). AMPH/TYR or PPA/TYR combinations further improved performance vs. either agent given alone. Microdialysis showed elevated hippocampal NE concentrations in response to hypothermia. TYR further elevated NE concentration in cold/restrained rats vs. saline (SAL)-treated controls. These results suggest that sympathomimetic agents, including the nutrient TYR, which enhance noradrenergic function, improve performance in animals acutely stressed by hypothermia.

Adrenergic alpha-Agonists↗

PubMed2001

Automated measurement of age-related changes in the locomotor response to environmental novelty and home-cage activity.

The likelihood to explore in an open-field environment decreases with age. Older animals tend to be less active and explore less both in novel and home-cage environments. The locomotor performance (fine movements, ambulatory movements, and rearing) of male Fischer 344 (F344) rats that were 6 (n=6) or 22 (n=6) months of age was evaluated by continuous automated counting of photobeam interruptions, every 30 min, during 60 consecutive hours, in standard polycarbonate cages. Novel environment performance was determined by photobeam interruption counting during the first hour in the new cage. The remaining 59 h were evaluated as home-cage activity. A significant age-related decrease in ambulatory and fine motor activity was seen during the first hour of testing (novel environment). In addition, aged rats showed a decreased number of ambulatory and fine movements in home-cage activity, predominantly during the dark portion of the light cycle and during or around both light-switch periods (05:00 and 17:00). No differences were seen in rearing behavior. These findings provide a more detailed analysis and additional evidence of the activity decreases and rhythmic changes seen in aged F344 rats under uninterrupted testing conditions.

Aging↗

PubMed2001

Effect of age on object exploration, habituation, and response to spatial and nonspatial change.

To measure their ability to detect novel arrangements in a given environment, young (6 months old) and senescent (22-24 months old) male F344 rats were repeatedly exposed to a given spatial configuration of objects contained in an open field. After the rats were habituated to the novel environment (1 trial with no objects, followed by 3 trials with 5 salient objects), the spatial arrangement of the objects was modified (2 trials), and object novelty was tested (2 trials) by substituting a familiar object with a new one at the same location (nonspatial change). The results indicated that the senescent rats explored old objects less than young rats, particularly on Trial 2. On the 1st trial with displaced objects (Trial 5), the senescent rats explored the displaced objects less than the young rats. However, when a new object was placed in the field (Trials 7-8), there were no age differences in new object exploration. These results suggest that senescent rats have decrements in the ability to build spatial representations of the environment and to use this information to detect such changes, even though object recognition is not impaired with age.

Aging↗

PubMed2001

Influence of photoperiod, laboratory caging and aging on plasma lipid response to an atherogenic diet among F1B hamsters.

The effects and interactions of photoperiod, animal caging, aging and diet on plasma lipid levels in male F1B hamsters were examined in the current study. Sixteen young and sixteen old animals were housed one or four per cage. Eight young animals from each housing group were placed in an animal room with either 12/12 h (PT-12) or 10/14 h (PT-10) light/dark cycle while the sixteen old animals were maintained under a PT-12 light cycle. Plasma cholesterol and triglyceride concentrations were determined in all animals after a 2-week period of acclimation on chow diet and following 4-week intervention on atherogenic diet. Baseline total cholesterol (TC) levels were 131+/-25 mg/dl and 142+/-39 mg/dl for young and old animals, respectively, while baseline triglyceride (Tg) levels were 202+/-48 mg/dl and 160+/-37 mg/dl respectively for the same animals. Following 4-weeks on an atherogenic diet, single-caged PT 12 animals had elevated but significantly lower TC levels than group-caged animals (161+/-30 mg/dl and 240 +/-58 mg/dl, respectively) while single and group housed PT10 animals had TC levels of 296+/-75 mg/dl and 351+/-124 mg/dl, respectively. Similarly, plasma Tg levels rose to 330+/-100 mg/dl and 486+/-200 mg/dl in single and group housed PT12 animals (respectively) and to 668+/-270 mg/dl and 545+/-199 mg/dl in single and group housed PT10 animals (respectively). No significant changes related to atherogenic diet were observed in plasma TC or Tg levels in the older animals. Although caging conditions influence the cholesterol and triglyceride response to the atherogenic diet (p<.05), light cycle photoperiod seems to exert a greater effect (p<.005). In conclusion, photoperiod length dramatically affects diet-induced plasma lipid concentrations in young male F1B hamsters, and thus needs be considered in experimental designs of animal-housed lipid research.

Aging↗

PubMed2001

Effects of exposure to 56Fe particles on the acquisition of a conditioned place preference in rats.

Exposure to low doses of 56Fe particles produces changes in neural function and behavior. The present experiments were designed to examine the effects of irradiation on the acquisition of a dopamine-mediated conditioned place preference (CPP). In the CPP procedure, rats are given an injection of the dopamine agonist amphetamine in one distinctive compartment and a saline injection in a different compartment of a three-compartment apparatus. Control rats develop a preference for the amphetamine-paired compartment. In contrast, rats exposed to 1 Gy of 56Fe particles fail to develop a similar preference. The results of the experiment indicate that exposure to low doses of heavy particles can disrupt the neural mechanisms that mediate the reinforcement of behavior.

Amphetamine↗

PubMed2000

Polyphenolics enhance red blood cell resistance to oxidative stress: in vitro and in vivo.

In this study we investigated the potential antioxidant properties of blueberry polyphenolics in vitro and vivo, using red blood cell (RBC) resistance to reactive oxygen species (ROS) as the model. In vitro incubation with anthocyanins or hydroxycinnamic acids (HCA) (0.5 and 0.05 mg/ml) was found to enhance significantly RBC resistance to H2O2 (100 microM) induced ROS production. This protection was also observed in vivo following oral supplementation to rats at 100 mg/ml. However, only anthocyanins were found to afford protection at a significant level, this at 6 and 24 h post supplementation. This protection was not consistent with the measured plasma levels of anthocyanins. Indeed, plasma polyphenolic concentrations were highest after 1 h, declining considerably after 6 h and not detected after 24 h. The difference in absorption between anthocyanins and HCA is likely to have contributed to the observed difference in their abilities to afford protection to RBC. This protection represents a positive role following dietary consumption of polyphenolics from blueberries, against ROS formation within RBC in vivo.

Animals↗

PubMed2000

Oxidative stress protection and vulnerability in aging: putative nutritional implications for intervention.

Research indicates that vulnerability to oxidative stress (OSV) may increase in aging, suggesting that age-related neurodegenerative diseases such as Alzheimer's disease (AD) or vascular dementia (VAD) may be superimposed upon a vulnerable neuronal environment. Determinations in cell models have suggested that the enhanced OSV may be the result of, (a) increases in membrane lipids, especially sphingomyelin and the sphingomyelin metabolite, sphingosine-1-phosphate, (b) decreases in glutathione, and (c) CNS distribution of OS-sensitive neuronal muscarinic receptor subtypes (e.g. M1, M2 and M4). These changes appear to enhance, (a) decrements in cellular calcium buffering following KCl-induced depolarization, and (b) cell death under OS conditions. Among the most effective agents that antagonized cellular OSV were the combination of polyphenolics found in fruits (e.g. blueberry extract) with high antioxidant activity. Subsequent experiments using dietary supplementation with fruit (strawberry) or vegetable (spinach) extracts have shown that such extracts are also effective in forestalling and reversing the deleterious effects of behavioral aging in F344 rats. Thus, it appears that the beneficial effects of the polyphenolics found in fruits and vegetables in neuronal aging and behavior may be similar to those seen with respect to carcinogenesis and cardiovascular disease.

Aging↗

PubMed2000

Antioxidant-rich diets improve cerebellar physiology and motor learning in aged rats.

The free radical theory of aging predicts that reactive oxygen species are involved in the decline in function associated with aging. The present paper reports that diets supplemented with either spinach, strawberries or blueberries, nutritional sources of antioxidants, reverse age-induced declines in beta-adrenergic receptor function in cerebellar Purkinje neurons measured using electrophysiological techniques. In addition the spinach diet improved learning on a runway motor task, previously shown to be modulated by cerebellar norepinephrine. Motor learning is important for adaptation to changes in the environment and is thus critical for rehabilitation following stroke, spinal cord injury, and the onset of some neurodegenerative diseases. These data are the first to indicate that age-related deficits in motor learning and memory can be reversed with nutritional interventions.

Aging↗

PubMed2000

CNS-induced deficits of heavy particle irradiation in space: the aging connection.

Our research over the last several years has suggested that young (3 mo) rats exposed to whole-body 56Fe irradiation show neuronal signal transduction alterations and accompanying motor behavioral changes that are similar to those seen in aged (22-24 mo) rats. Since it has been postulated that 1-2% of the composition of cosmic rays contain 56Fe particles of heavy particle irradiation, there may be significant CNS effects on astronauts on long-term space flights which could produce behavioral changes that could be expressed during the mission or at some time after the return. These, when combined with other effects such as weightlessness and exposure to proton irradiations may even supercede mutagenic effects. It is suggested that by determining mechanistic relationships that might exist between aging and irradiation it may be possible to determine the common factor(s) involved in both perturbations and develop procedures to offset their deleterious effects. For example, one method that has been effective is nutritional modification.

Aging↗