Biomedical subjects

B Shukitt-Hale

Publications and source records attributed to B Shukitt-Hale.

At least 19 recordsLinked to original sources

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

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↗

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

Effect of fruits, vegetables, or vitamin E--rich diet on vitamins E and C distribution in peripheral and brain tissues: implications for brain function.

Age-related neurodegenerative conditions are the principal cause of declining cognitive and motor function during aging. Evidence support that fruits and vegetables containing generous amounts of antioxidant nutrients are important for neurological function. We investigated the effect of diets enriched with fruits or vegetables but low in vitamin E and a diet high in vitamin E on the distribution of vitamins C and E in the brain and dopamine release of Fischer 344 rat model, over an 8-month period. The low-vitamin E diet resulted in lowered alpha-tocopherol levels in brain and peripheral tissues, whereas the animals that received a diet enriched in vitamin E showed a significant increase, between 500-900%. Vitamin C concentration in plasma, heart, and liver was reduced in the vitamin E-supplemented group. It is concluded that supplementation or depletion of alpha-tocopherol for 8 months results in marked changes in vitamin E levels in brain tissue and peripheral tissues, and varied distribution of alpha-tocopherol throughout the different brain regions examined. In addition, compared to control group, rats supplemented with strawberry, spinach, or vitamin E showed a significant enhancement in striatal dopamine release. These findings suggest that other nutrients present in fruits and vegetables, in addition to the well-known antioxidants, may be important for brain function.

Aging↗

PubMed2000

Spatial learning and memory deficits induced by exposure to iron-56-particle radiation.

It has previously been shown that exposing rats to particles of high energy and charge (HZE) disrupts the functioning of the dopaminergic system and behaviors mediated by this system, such as motor performance and an amphetamine-induced conditioned taste aversion; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, spatial learning and memory were assessed in the Morris water maze 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/nucleon high-energy (56)Fe particles, to test the cognitive behavioral consequences of radiation exposure. Irradiated rats demonstrated cognitive impairment compared to the control group as seen in their increased latencies to find the hidden platform, particularly on the reversal day when the platform was moved to the opposite quadrant. Also, the irradiated group used nonspatial strategies during the probe trials (swim with no platform), i.e. less time spent in the platform quadrant, fewer crossings of and less time spent in the previous platform location, and longer latencies to the previous platform location. These findings are similar to those seen in aged rats, suggesting that an increased release of reactive oxygen species may be responsible for the induction of radiation- and age-related cognitive deficits. If these decrements in behavior also occur in humans, they may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

Analysis of Variance↗

PubMed1999

Effect of vitamin E intake on levels of vitamins E and C in the central nervous system and peripheral tissues: implications for health recommendations.

Vitamin E (alpha-gamma-tocopherol) is an important component in biological membranes. A decrease in its concentration imposes structural and functional damage to the cells. The object of this study was to assess the effect of a graded dietary vitamin E (E) intake on E concentration in specific regions of the brain, and its influence on vitamin C levels and neurological function. Following a 2-month period, rats supplemented with 5, 30, 60, 250 or 500 mg all-rac-alpha-tocopherol-acetate/kg diet (mg E/kg diet) exhibited a significant increase of E concentration in brain and peripheral tissues. However, while blood and liver showed a dose response increase in E concentration which correlated well with the different levels of E in the diet, the central nervous system (CNS) followed the same pattern of increase of vitamin E in brain tissue only when the diet was supplemented with 5, 30, or 60 mg E/kg diet. No further increase in E concentration was observed when the diet was supplemented with 250 or 500 mg E/kg diet. Similarly, the heart tissue showed a significant increase in its E concentration when the was enriched with 5, 30, or 60 mg E/kg diet, with no further increases at 250 or 500 mg. Vitamin C concentration in brain cortex and cerebellum, plasma, liver, and heart was reduced in the groups receiving 250 or 500 mg E/kg diet. Compared to the low E group, rats supplemented with the 60, 250 or 500 mg E/kg diet showed a significant enhancement in striatal dopamine (DA) release, but no differences were observed among the latter three groups.

Animals↗

PubMed1999

Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation.

Ample research indicates that age-related neuronal-behavioral decrements are the result of oxidative stress that may be ameliorated by antioxidants. Our previous study had shown that rats given dietary supplements of fruit and vegetable extracts with high antioxidant activity for 8 months beginning at 6 months of age retarded age-related declines in neuronal and cognitive function. The present study showed that such supplements (strawberry, spinach, or blueberry at 14.8, 9.1, or 18.6 gm of dried aqueous extract per kilogram of diet, respectively) fed for 8 weeks to 19-month-old Fischer 344 rats were also effective in reversing age-related deficits in several neuronal and behavioral parameters including: oxotremorine enhancement of K(+)-evoked release of dopamine from striatal slices, carbachol-stimulated GTPase activity, striatal Ca(45) buffering in striatal synaptosomes, motor behavioral performance on the rod walking and accelerod tasks, and Morris water maze performance. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging.

Aging↗

PubMed1999

Effects of aging on cerebellar noradrenergic function and motor learning: nutritional interventions.

Aging is associated with a decline in motor coordination and the ability to learn new motor learning skills. This loss of function is correlated with a decline in cerebellar beta-adrenergic receptor function. We have examined the role of oxidative stress on this system by exposing young rats to normobaric hyperoxia. This exogenous oxidative insult results in a decline in cerebellar beta-adrenergic receptor function that resembles what is observed in normal aged rats. This effect of hyperoxia is blocked by antioxidants. We have also examined the effects of nutritional supplementation of aged rats with diets high in antioxidant capacity. Foods such as blueberries and spinach can prevent and/or reverse age-related declines in cerebellar noradrenergic receptor function.

Action Potentials↗

PubMed1999

The effects of dietary antioxidants on psychomotor performance in aged mice.

Male C57BL/6NIA mice were provided one of six different antioxidant diets: vitamin E, glutathione, vitamin E plus glutathione, melatonin, strawberry extract, or control, beginning at 18 months of age. A battery of motor tests--rod walk, wire hang, plank walk, and inclined screen-was administered either: 1) before dietary treatment and then 6 months later at 24 months of age: or 2) only after 6 months of dietary treatment at age 24 months. An untreated group of 4-month-old mice served as young controls. Psychomotor performance was lower in 18-month-old mice compared with 4-month-old mice in the rod walk, wire hang, and inclined screen tests; however, no further decline was seen from 18 to 24 months on any measure. Chronic dietary antioxidant treatments were not effective in reversing age-related deficits in psychomotor behavior, except for the glutathione diet on inclined screen performance. It seems that motor performance deteriorates profoundly with age, because deficits at 18 months of age were as severe as they were at 24 months, and these age-associated motor deficits may be difficult to reverse, even with antioxidant treatment.

Aging↗

PubMed1999

Effect of normobaric hyperoxia on two indexes of synaptic function in Fisher 344 rats.

The physiological response of two central nervous system neurotransmitter receptors to oxidative stress was studied using the rat model of hyperoxia. We show that hyperoxia leads to a decline in the ability of isoproterenol (ISO) to augment GABAergic responses in cerebellar Purkinje neurons in vivo. This effect is reversed by the N-tert-butylalpha-phenylnitrone (PBN). We also show that hyperoxia produces a decline in the ability of oxotremorine (OXO) to stimulate dopamine (DA) release in striatal slices. This effect is accompanied by an increase in hydroxyl radical levels in the CNS reflected in an increase in 2,3-DHBA, suggesting that the change is the result of an increased level of oxidative stress. We also show a time dependent effect of hyperoxia on both beta-adrenergic and muscarinic receptor function. We examined the interaction between age and hyperoxia exposure and found that in 12-month-old rats there is a decline in the baseline response prior to oxygen exposure that may interfere with observing a subsequent effect of hyperoxia. Differential effects were observed between the cerebellum and striatum with respect to the interaction of age and time of oxygen exposure. Overall, the data suggest that age and hyperoxia may be acting via a common mechanism because there was no synergistic effect of the two conditions.

Animals↗

PubMed1999

Hyperoxia-induced changes in antioxidant capacity and the effect of dietary antioxidants.

We investigated, by measuring oxygen radical absorbance capacity (ORAC), whether hyperoxia causes alterations in antioxidant status and whether these alterations could be modulated by dietary antioxidants. Rats were fed for 8 wk a control diet or a control diet supplemented with vitamin E (500 IU/kg) or with aqueous extracts (ORAC: 1.36 mmol Trolox equivalents/kg) from blueberries or spinach and then were exposed to air or >99% O2 for 48 h. Although the constituents of the extracts were not extensively characterized, HPLC indicated that blueberry extract was particularly rich in anthocyanins, and the spinach extract did not contain any anthocyanins. The ORAC was determined in samples without proteins [serum treated with perchloric acid (PCA); ORACPCA] and with proteins (ORACtot). Hyperoxia induced a decrease in serum protein concentration, an increase in serum ORACPCA, decreases in lung ORACPCA and ORACtot, and an equilibration of proteins and ORACPCA between serum and pleural effusion. These alterations suggested a redistribution of antioxidants between tissues and an increase in capillary permeability during hyperoxia. Only the blueberry extract was effective in alleviating the hyperoxia-induced redistribution of antioxidants between tissues.

Animals↗

PubMed1999

Magnesium activation of GTP hydrolysis or incubation in S-adenosyl-l-methionine reverses iron-56-particle-induced decrements in oxotremorine enhancement of K+-evoked striatal release of dopamine.

Previous research has determined that the deficits in motor behavior seen in aged animals irradiated with (56)Fe particles involved alterations in muscarinic receptor sensitivity. In the present experiments, we determined whether increasing either membrane fluidity by exposure of striatal slices from irradiated ((56)Fe particles) animals to S-adenosyl-l-methionine (SAM) or GTP hydrolysis with Mg(2+) would reverse this (56)Fe-particle-induced loss of muscarinic receptor sensitivity, as has been observed in aged animals. Results indicated that, while increasing Mg(2+) concentrations in the incubation medium was effective in reducing the radiation effects, SAM was able to effect some reversal of the radiation effects only at the lower concentration (200 microM). These results suggest that similar mechanisms may be involved in the deficits in signal transduction seen after (56)Fe-particle irradiation to those seen in aging, and that these may include changes in the membrane structure or composition that could alter subsequent responsiveness of transduction pathways. The results further suggest that, as has been reported previously, (56)Fe-particle irradiation may accelerate brain aging, and that since these HZE particles contribute at least 1% of the dose that astronauts would receive from cosmic rays, long-term exposure on extended space flights (e.g. to Mars) may produce similar deficits that could have immediate or delayed effects on behavior.

Animals↗

PubMed1998

Membrane and receptor modifications of oxidative stress vulnerability in aging. Nutritional considerations.

Evidence suggests that oxidative stress (OS) may contribute to the pathogenesis of age-related decrements in neuronal function and that OS vulnerability increases as a function of age. In addition to decreased endogenous protection, increases in OS vulnerability may result from changes in membrane lipids and distribution of receptor subtype. Using a PC-12 cell model system, we have shown that H2O2 or dopamine (DA) exposure induced deficits in the cell's ability to clear (extrude/sequester, E/S) Ca2+ that are similar to those seen in aging. When plasma membrane concentrations of sphingomyelin (SPM) were used, the SPM metabolite, sphingosine-1-phosphate was increased to the same levels as those seen in aging, and enhancement of OS-induced decreases in calcium E/S following KCL depolarization was observed. Differential decreases in CA2+ E/S were also seen following DA-induced OS in COS-7 cells transfected with one of five muscarinic receptor subtypes. Cells transfected with either M1, M2, or M4 receptors showed significantly greater vulnerability to OS (as expressed by greater decrements in calcium E/S and cell death) than those transfected with M3 or M5 receptors. The vitamin E analogue, Trolox, and the nitrone-trapping agent, PBN, were not effective in altering E/S decrements but were effective in preventing cell death 24 h after OS exposure. These findings suggest that putative regional (e.g., striatum and hippocampus) increases in OS vulnerability and loss of neuronal function in aging may be dependent upon membrane SPM concentration and receptor subtype. In related studies, attempts were made to determine whether increased OS protection via nutritional increases in antioxidant levels in rats [using diets supplemented with vitamin E (500IU/kg), strawberry extracts (9.4 g/kg dried aqueous extract, DAE), spinach (6.7 g/kg DAE), or blueberry extracts (10 g/kg DEA for six weeks)] would protect against exposure to 100% O2 (a model of accelerated neuronal aging). Results indicated that these diets were effective in preventing OS-induced decrements in several parameters (e.g., nerve growth factor decreases), suggesting that although there may be increases in OS vulnerability in aging, phytochemicals present in antioxidant-rich foods may be beneficial in reducing or retarding the functional central nervous system deficits seen in aging or oxidative insult.

Aging↗

PubMed1998

Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits.

Recent research has indicated that increased vulnerability to oxidative stress may be the major factor involved in CNS functional declines in aging and age-related neurodegenerative diseases, and that antioxidants, e.g., vitamin E, may ameliorate or prevent these declines. Present studies examined whether long-term feeding of Fischer 344 rats, beginning when the rats were 6 months of age and continuing for 8 months, with diets supplemented with a fruit or vegetable extract identified as being high in antioxidant activity, could prevent the age-related induction of receptor-mediated signal transduction deficits that might have a behavioral component. Thus, the following parameters were examined: (1) oxotremorine-enhanced striatal dopamine release (OX-K+-ERDA), (2) cerebellar beta receptor augmentation of GABA responding, (3) striatal synaptosomal 45Ca2+ clearance, (4) carbachol-stimulated GTPase activity, and (5) Morris water maze performance. The rats were given control diets or those supplemented with strawberry extracts (SE), 9.5 gm/kg dried aqueous extract (DAE), spinach (SPN 6.4 gm/kg DAE), or vitamin E (500 IU/kg). Results indicated that SPN-fed rats demonstrated the greatest retardation of age-effects on all parameters except GTPase activity, on which SE had the greatest effect, whereas SE and vitamin E showed significant but equal protection against these age-induced deficits on the other parameters. For example, OX-K+-ERDA enhancement was four times greater in the SPN group than in controls. Thus, phytochemicals present in antioxidant-rich foods such as spinach may be beneficial in retarding functional age-related CNS and cognitive behavioral deficits and, perhaps, may have some benefit in neurodegenerative disease.

Aging↗

PubMed1998

Sub-regional hippocampal vulnerability in various animal models leading to cognitive dysfunction.

Various animal models, involving different brain insults, lead to memory deficits, which can be measured using behavioral tests. In numerous studies, using five different experimental models in rats, we have found that cognitive dysfunction is invariably accompanied by hippocampal CA1 and CA3 pyramidal cells degeneration. However, of these two, the most affected area changes from one model to the other. The present manuscript describes and compares the morphological alterations within the hippocampus in the following experimental models: normal aging, hypoxia, prolonged corticosterone administration, brain ischemia and cholinesterase (ChE) inhibition. In all the above, many hippocampal neurons were severely damaged, however, CA3 pyramidal cells were mostly affected in normal aging and following hypobaric hypoxia, whereas CA1 cells were especially affected following corticosterone administration, global ischemia and ChE inhibition. Several mechanisms, which might be involved in the diverse courses of the lesions are being considered: cerebral oxygen and glucose, glutamate neurotoxicity and calcium involvement. It is anticipated that elucidation of the specific role of CA1 and CA3 hippocampal sub-fields in the various experimental models might help in understanding processes such as age-related neuronal degeneration and assist in their prevention.

Aging↗

PubMed1998

Spatial memory under acute cold and restraint stress.

This study examined spatial memory as measured by radial arm maze (RAM) performance after exposure to two stress conditions and a normothermic-unrestrained control condition. Male Fischer 344 rats were trained on the win-shift RAM procedure for 7 days, by which time they achieved asymptotic performance. The next day, rats in the two stress groups were exposed to 15 min of restraint in either 37 degrees C water (normothermic-restraint) or in 20 degrees C water (cold-restraint). Rats were then allowed 40 min in a dry cage before being tested in the RAM. Performance was measured using the following dependent variables: number of correct out of the first eight choices, total number of choices, and time per choice. There were statistically significant effects of stress on all these variables; performance decrements were observed in both stress conditions relative to the normothermic-unrestrained condition. Normothermic-restrained rats displayed less impairment than cold-restrained rats on the stress day. Performance of normothermic-restrained rats returned to baseline levels the day after stress, whereas performance for the cold-restrained rats typically did not. This study demonstrates that: 1) restraint and cold stress impair performance on a memory task; and 2) impairment extent is related to stress severity. One of the mechanisms responsible for the observed behavioral deficits under cold stress may involve altered cholinergic function, because we previously demonstrated that hippocampal acetylcholine levels also decrease in relation to the severity of cold stress.

Animals↗