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Biomedical subjects

B E Levin

Publications and source records attributed to B E Levin.

At least 19 recordsLinked to original sources
PubMed2006

Differential effects of exercise on body weight gain and adiposity in obesity-prone and -resistant rats.

OBJECTIVE: To determine the effect of exercise on weight gain and adiposity in obesity-prone and -resistant rats. DESIGN: Body weight gain, fat pad weights, food intake, plasma leptin and insulin levels were assessed in outbred male Sprague-Dawley rats, which remained sedentary or were given unrestricted access to running wheels either before or after they developed diet-induced obesity (DIO) or diet-resistance (DR) on a high energy (HE; 31% fat) diet. RESULTS: When fed a low fat (4.5%) chow diet, rats which would later develop DIO (n=6) after 3 weeks on HE diet ran the same amount as DR rats (n=6). Other rats were first made DIO (n=12) or DR (n=12) after 10 weeks on HE diet and then either kept sedentary or given running wheels for 4 weeks on HE diet. DIO and DR rats ran comparable amounts but only the DIO rats reduced their body weight gain, fat pad relative to body weights and plasma leptin levels significantly, compared to their sedentary controls. Exercise had no effect on food intake in either DIO or DR rats but reduced feed efficiency (weight gain/caloric intake) in both. CONCLUSION: Although DIO and DR rats ran similar amounts, the greater reduction in body weight gain and adiposity of exercising DIO rats suggests that they are more sensitive to some metabolic or physiologic system that prevents them from increasing their intake sufficiently to compensate for their net reduction in energy stores.

Adiposity↗
PubMed2004

Beta oxidation in the brain is required for the effects of non-esterified fatty acids on glucose-induced insulin secretion in rats.

AIMS/HYPOTHESIS: NEFA play a key role in the setting of insulin resistance and hyperinsulinaemia, which are both features of the prediabetic state. In addition to the direct effects on pancreas and peripheral tissues, NEFA have been reported to act via changes in autonomic nervous system activity. The present study was aimed at studying the effects of a local increase in NEFA in the brain on glucose-induced insulin secretion (GIIS) and on insulin action. We hypothesised that cerebral NEFA beta oxidation is a prerequisite for these central effects. METHODS: Male Wistar rats were infused with Intralipid/heparin for 24 h through the carotid artery towards the brain (IL rats), after which we performed the GIIS test, a euglycaemic-hyperinsulinaemic clamp and c-fos immunochemistry. In another series of experiments, Intralipid/heparin infusion was coupled with lateral ventricular infusion of etomoxir, a CPT1 inhibitor, which was initiated 5 days previously. RESULTS: During the infusion period, there were no changes in plasma NEFA, insulin or glucose concentrations. IL rats displayed an increased GIIS compared with control rats (C rats) infused with saline/heparin, and their liver insulin sensitivity was decreased. Furthermore, lipid infusion induced a significant decrease in c-fos-like immunoreactive neurons in medial hypothalamic nuclei, and an increase in lateral hypothalamus. Neuronal activation profile was almost normalised in IL rats infused with etomoxir, and GIIS was strongly decreased, possibly because of the concomitant normalisation of hepatic glucose output. CONCLUSIONS/INTERPRETATION: These results strongly suggest that beta oxidation is required for the central effects of NEFA on GIIS.

Animals↗
PubMed2004

PTSD symptoms and onset of neurologic disease in elderly trauma survivors.

In this case study, we present two Holocaust survivors who appeared to have adapted well post-trauma, but developed severe PTSD symptomatology following the onset of neurologic illness in later life. These individuals were referred fro neuropsychological evaluations by their treating neurologists to assess their levels of cognitive functioning. We present the neuropsychological findings, and discuss possible mechanisms for emergence of PTSD symptoms. These case studies demonstrate the need for systematic research to further investigate the potential relationship between aging, degenerative disease, and PTSD symptoms in elderly trauma survivors.

Age of Onset↗
PubMed2004

The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides.

Glucosensing neurons in the hypothalamic arcuate nucleus (ARC) were studied using electrophysiological and immunocytochemical techniques in neonatal male Sprague-Dawley rats. We identified glucose-excited and -inhibited neurons, which increase and decrease, respectively, their action potential frequency (APF) as extracellular glucose levels increase throughout the physiological range. Glucose-inhibited neurons were found predominantly in the medial ARC, whereas glucose-excited neurons were found in the lateral ARC. ARC glucose-excited neurons in brain slices dose-dependently increased their APF and decreased their ATP-sensitive K+ channel (KATP channel) currents as extracellular glucose levels increased from 0.1 to 10 mmol/l. However, glucose sensitivity was greatest as extracellular glucose decreased to <2.5 mmol/l. The glucokinase inhibitor alloxan increases KATP single-channel currents in glucose-excited neurons in a manner similar to low glucose. Leptin did not alter the activity of ARC glucose-excited neurons. Although insulin did not affect ARC glucose-excited neurons in the presence of 2.5 mmol/l (steady-state) glucose, they were stimulated by insulin in the presence of 0.1 mmol/l glucose. Neuropeptide Y (NPY) inhibited and alpha-melanocyte-stimulating hormone stimulated ARC glucose-excited neurons. ARC glucose-excited neurons did not show pro-opiomelanocortin immunoreactivity. These data suggest that ARC glucose-excited neurons may serve an integrative role in the regulation of energy balance.

Alloxan↗
PubMed2001

Glucosensing neurons do more than just sense glucose.

The brain regulates energy homeostasis by balancing energy intake, expenditure and storage. To accomplish this, it has evolved specialized neurons that receive and integrate afferent neural and metabolic signals conveying information about the energy status of the body. These sensor-integrator-effector neurons are located in brain areas involved in homeostatic functions such as the hypothalamus, locus coeruleus, basal ganglia, limbic system and nucleus tractus solitarius. The ability to sense and regulate glucose metabolism is critical because of glucose's primacy as a metabolic substrate for neural function. Most neurons use glucose as an energy substrate, but glucosensing neurons also use glucose as a signaling molecule to regulate neuronal firing and transmitter release. There are two types of glucosensing neurons that either increase (glucose responsive, GR) or decrease (glucose sensitive, GS) their firing rate as brain glucose levels rise. Little is known about the mechanism by which GS neurons sense glucose. However, GR neurons appear to function much like the pancreatic beta-cell where glycolysis regulates the activity of an ATP-sensitive K(+) (K(ATP)) channel. The K(ATP) channel is composed of four pore-forming units (Kir6.2) and four sulfonylurea binding sites (SUR). Glucokinase (GK) appears to modulate K(ATP) channel activity via its gatekeeper role in the glycolytic production of ATP. Thus, GK may serve as a marker for GR neurons. Neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus are critical components of the energy homeostasis pathways in the brain. Both express Kir6.2 and GK, as well as leptin receptors. They also receive visceral neural and intrinsic neuropeptide and transmitter inputs. Such metabolism-related signals can summate upon K(ATP) channel activity which then alters membrane potential, neuronal firing rate and peptide/transmitter release. The outputs of these neurons are integral components of effector systems which regulate energy homeostasis. Thus, arcuate NPY and POMC neurons are probably prototypes of this important class of sensor-integrator-effector neurons.

Animals↗
PubMed2001

Application of the multilingual aphasia examination-spanish in the evaluation of Hispanic patients post closed-head trauma.

Despite the rapid increase of Hispanics in the U.S., there continues to be a lack of adequate psychological assessment tools to examine Spanish-speaking patients with cognitive or neuropsychological disturbances. We investigated the clinical utility of the Multilingual Aphasia Examination-Spanish (MAE-S) in the evaluation of language functions of Hispanic subjects post-traumatic brain injury (TBI). The performance of 40 TBI patients was compared to that of 40 age-, gender-, and education-matched normal controls. Subject groups differed on the Visual Naming (VN), Controlled Oral Word Association (COWA), and Token Test subtests. The VN and COWA subtests were the best discriminators of group membership. Distribution of scores for the patient group on the Rating of Articulation scale additionally indicate subtle articulatory difficulties post-TBI. For all subtests, trauma severity per Glasgow Coma Scale was the best predictor of language performance, over and above the contribution of other clinical and demographic variables. These results are consistent with prior reports of dysphasia post-TBI and suggest that the MAE-S is a sensitive and accurate measure to assess language disturbances in Hispanic populations.

Adult↗
PubMed2001

Convergence of pre- and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus.

Glucosensing neurons in the ventromedial hypothalamic nucleus (VMN) were studied using visually guided slice-patch recording techniques in brain slices from 14- to 21-day-old male Sprague-Dawley rats. Whole-cell current-clamp recordings were made as extracellular glucose levels were increased (from 2.5 to 5 or 10 mmol/l) or decreased (from 2.5 to 0.1 mmol/l). Using these physiological conditions to define glucosensing neurons, two subtypes of VMN glucosensing neurons were directly responsive to alterations in extracellular glucose levels. Another three subtypes were not directly glucose-sensing themselves, but rather were presynaptically modulated by changes in extracellular glucose. Of the VMN neurons, 14% were directly inhibited by decreases in extracellular glucose (glucose-excited [GE]), and 3% were directly excited by decreases in extracellular glucose (glucose-inhibited [GI]). An additional 14% were presynaptically excited by decreased glucose (PED neurons). The other two subtypes of glucosensing neurons were either presynaptically inhibited (PIR; 11%) or excited (PER; 8%) when extracellular glucose was raised to > 2.5 mmol/l. GE neurons sensed decreased glucose via an ATP-sensitive K(+) (K(ATP)) channel. The inhibitory effect of increased glucose on PIR neurons appears to be mediated by a presynaptic gamma-aminobutyric acid-ergic glucosensing neuron that probably originates outside the VMN. Finally, all types of glucosensing neurons were both fewer in number and showed abnormal responses to glucose in a rodent model of diet-induced obesity and type 2 diabetes.

Adenosine Triphosphate↗
PubMed2000

Glucose-regulated dopamine release from substantia nigra neurons.

Glucose modulates substantia nigra (SN) dopamine (DA) neuronal activity and GABA axon terminal transmitter release by actions on an ATP-sensitive potassium channel (K(ATP)). Here, the effect of altering SN glucose levels on striatal DA release was assessed by placing microdialysis probes into both the SN and striatum of male Sprague-Dawley rats. Reverse dialysis of 20 mM glucose through the SN probes transiently decreased striatal DA efflux by 32% with a return to baseline after 45 min despite constant glucose levels. During 50 mM glucose infusion, striatal DA efflux increased transiently by 50% and returned to baseline after 60 min. Infusion of 100 mM glucose produced a transient 25% decrease in striatal DA efflux followed by a sustained 50% increase above baseline. Efflux increased by a further 30% when the GABA(A) antagonist bicuculline (50 microM) was added to the 100 mM glucose infusate. At basal glucose levels, nigral bicuculline alone raised striatal DA efflux by 31% suggesting a tonic GABA inhibitory input to the DA neurons. The sulfonylurea glipizide (50 microM) produced a transient 25% increase in striatal DA release that became sustained when bicuculline was added. Thus, striatal DA release is affected by changing SN glucose levels. This response may well reflect the known effect of glucose on K(ATP) channel activity on both SN DA neurons and GABA axon terminals in the substantia nigra. These interactions could provide a mechanism whereby glucose modulates motor activity involved in food intake.

Animals↗
PubMed2000

Cognitive outcome of children with epilepsy and malformations of cortical development.

OBJECTIVE: To assess intellectual functioning (IQ) in 54 children and adolescents with intractable epilepsy who later underwent cortical resection due to unilateral malformations of cortical development acquired in utero. METHODS: Lesion type was classified into circumscribed mass lesions and diffuse cortical dysplasia based on histopathologic analysis of surgical tissue. Cortical dysplastic lesions were further graded as mild, moderate, or severe according to specific microscopic features. Laterality of lesion was determined through neurologic examination and electrophysiologic and neuroradiologic procedures. Classification of lesion type was corroborated by its significant relationship with other disease-related variables known to be related to clinical severity (age at seizure onset, age at resection, and extent of lesion). RESULTS: Analyses of covariance revealed that circumscribed lesions had a less deleterious effect on nonverbal IQ than did diffuse cortical dysplasia, after controlling for age at seizure onset and extent of lesion. This effect was also found on verbal IQ measures, but only in subjects with right-sided lesions. Subjects with left-sided lesions performed significantly more poorly on verbal IQ measures than those with right-sided lesions. Additionally, younger age at onset and greater extent of lesion were associated with poorer cognitive outcome. CONCLUSIONS: Cortical dysplasia and early left hemisphere lesions have a significantly worse impact on cognitive functioning than circumscribed lesions or right hemisphere developmental lesions in children with epilepsy.

Adolescent↗
PubMed2000

Metabolic imprinting on genetically predisposed neural circuits perpetuates obesity.

There is an obesity epidemic in the industrialized world that is not simply explained by excess energy intake and decreased energy expenditure. Persistent obesity develops when genetically predisposed individuals are in a chronic state of positive energy balance. Once established, the obese body weight is avidly defended against both over- and underfeeding. Animal studies have shown that lean individuals who are genetically predisposed toward obesity have abnormalities of neural function that prime them to become obese when caloric density of the diet is raised. These neural abnormalities are gradually "corrected" as obesity becomes fully developed, suggesting that obesity is the normal state for such individuals. Thus, defense of the obese body weight may be perpetuated by the formation of new neural circuits involved in energy-homeostasis pathways that are not then easily abolished. Such neural plasticity can occur in both adult life and during nervous-system development. Early pre- and postnatal metabolic conditions (maternal diabetes, obesity, undernutrition) can lead genetically predisposed offspring to become even more obese as adults. This enhanced obesity is associated with altered brain neural circuitry, and these changes can then be passed on to subsequent generations in a feed-forward cycle of ever-increasing body weight. Thus, the metabolic perturbations associated with obesity during both brain development and adult life can produce "metabolic imprinting" on genetically predisposed neural circuits involved in energy homeostasis. Drugs that reduce body weight decrease the defended body weight and alter neural pathways involved in energy homeostasis but have no permanent effect on body weight or neural function in most individuals. Thus, early intervention in mothers, infants, children, and adults may be the only way to prevent the formation of permanent neural connections that promote and perpetuate obesity in genetically predisposed individuals.

Animals↗
PubMed2000

The obesity epidemic: metabolic imprinting on genetically susceptible neural circuits.

The apparent obesity epidemic in the industrialized world is not explained completely by increased food intake or decreased energy expenditure. Once obesity develops in genetically predisposed individuals, their obese body weight is avidly defended against chronic caloric restriction. In animals genetically predisposed toward obesity, there are multiple abnormalities of neural function that prime them to become obese when dietary caloric density and quantity are raised. Once obesity is fully developed, these abnormalities largely disappear. This suggests that obesity might be the normal state for such individuals. Formation of new neural circuits involved in energy homeostasis might underlie the near permanence of the obese body weight. Such neural plasticity can occur during both nervous system development and in adult life. Maternal diabetes, obesity, and undernutrition have all been associated with obesity in the offspring of such mothers, especially in genetically predisposed individuals. Altered brain neural circuitry and function often accompanies such obesity. This enhanced obesity may then be passed on to subsequent generations in a feed-forward, upward spiral of increasing body weight across generations. Such findings suggest a form of "metabolic imprinting" upon genetically predisposed neural circuits involved in energy homeostasis. Centrally acting drugs used for obesity treatment lower the defended body weight and alter the function of neural pathways involved in energy homeostasis. But they generally have no permanent effect on body weight or neural function. Thus, early identification of obesity-prone mothers, infants, and adults and treatment of early obesity may be the only way to prevent the formation of permanent neural connections that promote and perpetuate obesity in genetically predisposed individuals.

Animals↗
PubMed2000

Defective dietary induction of uncoupling protein 3 in skeletal muscle of obesity-prone rats.

OBJECTIVE: The goal of this study was to determine whether differential induction of skeletal muscle uncoupling protein 3 (UCP3) contributes to the development of diet-induced obesity (DIO) or resistance to the development of obesity (DR) when rats are placed on a moderate fat (31%) high energy (HE) diet. RESEARCH METHODS AND PROCEDURES: Gastrocnemius muscle was obtained from Sprague-Dawley rats that were identified as DIO-prone (n = 5) or DR (n = 5) on the basis of urinary norepinephrine excretion while consuming a chow diet. Muscle was also obtained from animals in the top tertile of weight gain (DIOHE, n = 5) and the bottom tertile of weight gain (DRHE, n = 5) after 2 weeks on the HE diet. UCP3 and actin mRNA levels were measured in all muscle samples by Northern analysis. To distinguish the effect of dietary energy content from the effect of obesity itself, we studied additional DIO and DR animals that had been returned to a chow diet for 10 weeks after consuming a HE diet for 10 weeks. RESULTS: The muscle UCP3/actin mRNA ratio in animals that resisted the development of obesity during 2 weeks on the HE diet was 3-fold higher than in the other groups (DRHE = 3.24 +/- 0.83, DIOHE = 0.91 +/- 0.20, DIO-prone = 0.72 +/- 0.15, DR = 0.63 +/- 0.15; p = 0.002). However, there was no difference in muscle UCP3/actin mRNA ratios between DIO animals and DR animals that had been fed the HE diet for 10 weeks and then returned to either an ad libitum chow diet for 10 weeks (DIO = 13.8 +/- 3.53, DR = 11.1 +/- 3.43, p = NS) or to a restricted chow diet for 10 weeks (DIO = 11.0 +/- 2.85, DR = 10.6 +/- 2.20, p = NS) despite significantly greater body weight of the DIO animals. DISCUSSION: DR animals may initially resist weight gain when placed on a HE diet through a greater induction of muscle UCP3. This induction is transient and is related more closely to dietary fat content than to body fat stores. DIO animals show no initial induction of muscle UCP3, which may contribute to their increased metabolic efficiency soon after exposure to a HE diet.

Actins↗
PubMed2000

Cognitive decline affects subject attrition in longitudinal research.

We evaluated prospectively 210 patients with idiopathic Parkinson's disease (PD) to determine whether cognitive deterioration and disease disability affect subject drop out. Subjects who refused to return for follow-up testing had a greater degree of bradykinesia and overall disability, more advanced disease, fewer years of education and greater depressive symptomatology. However, discriminant analysis indicated that performance on the neuropsychological measures, rather than PD severity, significantly predicted whether patients return for follow-up testing. Our findings indicate that cognitive impairment uniquely contributes to subject attrition, which may distort dementia estimates in PD.

Aged↗
PubMed2000

Defense of body weight against chronic caloric restriction in obesity-prone and -resistant rats.

Half of Sprague-Dawley rats develop and defend diet-induced obesity (DIO) or diet resistance (DR) when fed a high-energy (HE) diet. Here, adult male rats were made DIO or DR after 10 wk on HE diet. Then half of each group was food restricted for 8 wk on chow to maintain their body weights at 90% of their respective baselines. Rate and magnitude of weight loss were comparable, but maintenance energy intake and the degree of sympathetic activity (24-h urine norepinephrine) inhibition were 17 and 29% lower, respectively, in restricted DR than DIO rats. Restricted DIO rats reduced adipose depot weights, plasma leptin, and insulin levels by 35%. Restricted DR rats reduced none of these. When fed ad libitum, both DR and DIO rats returned to the body weights of their respective chow-fed phenotype controls within 2 wk. This was associated with increased adipose mass and leptin and insulin levels only in DIO rats. Thus DR rats appear to alter primarily their lean body mass, whereas DIO rats primarily alter their adipose mass during chronic caloric restriction and refeeding.

Adipose Tissue↗
PubMed2000

Differential stress responsivity in diet-induced obese and resistant rats.

The relationship between stress and obesity was assessed in male rats selectively bred to develop either diet-induced obesity (DIO) or diet resistance (DR) when fed a high-energy, 31% fat diet for 3 wk followed by 2 wk on a hyperphagic liquid diet (Ensure). One-half of the rats of each phenotype were subjected to moderate daily, unpredictable stress (cage changing, exposure to conspecific, swim, and immobilization stress, intraperitoneal saline injection) during the 5 wk. Both stressed and unstressed DIO rats were 26% heavier and ate 27% more than comparable DR rats at onset and had 48% lower basal morning plasma corticosterone levels. Stressed DR rats gained less weight and had significant elevations of basal morning corticosterone but reduced basal sympathetic activity (24-h urine norepinephrine) over 5 wk compared with their unstressed DR controls. Terminally, there was a 35% increase in the paraventricular nucleus corticotropin-releasing hormone mRNA expression. On the other hand, stressed DIO rats showed only a transient early increase in open-field activity and a terminal increase in basal corticosterone levels as the only effects of stress. Thus DIO rats are hyporesponsive to chronic stress compared with DR rats. This is in keeping with several other known differences in hypothalamopituitary and autonomic function in this model.

Animals↗
PubMed2000

Sibutramine alters the central mechanisms regulating the defended body weight in diet-induced obese rats.

Chronic administration of sibutramine lowers body weight, presumably by altering brain monoamine metabolism. Here the effect of sibutramine on sympathoadrenal function (24-h urine norepinephrine and epinephrine levels) and arcuate nucleus (ARC) neuropeptide Y (NPY) and proopiomelanocortin (POMC) expression was assessed in diet-induced obese rats fed a low-fat diet. Chronic (10 wk) sibutramine [5 mg. kg(-1). day(-1) ip; rats fed ad libitum and injected with sibutramine (AS)] lowered body weight by 15% but only transiently (3-4 wk) reduced intake compared with vehicle-treated controls [rats fed chow ad libitum and injected with vehicle daily (AV)]. Other rats food restricted (RS) to 90% of the weight of AS rats and then given sibutramine restored their body weights to the level of AS rats when allowed libitum food intake. After reequilibration, RS rats were again energy restricted to reduce their weight to 90% of AS rats, and additional vehicle-treated rats (RV) were restricted to keep their body weights at the level of AS rats for 3 wk more. Terminally, total adipose depot weights and leptin levels paralleled body weights (AV > AS = RV > RS), although AS rats had heavier abdominal and lighter peripheral depots than RV rats of comparable body weights. Sibutramine treatment increased sympathetic activity, attenuated the increased ARC NPY, and decreased POMC mRNA levels induced by energy restriction in RV rats. Thus sibutramine lowered the defended body weight in association with compensatory changes in those central pathways involved in energy homeostasis.

Adipose Tissue↗