Biomedical subjects

B E Levin

Publications and source records attributed to B E Levin.

At least 109 records · Page 6Linked to original sources

PubMed1989

Cognitive impairments associated with early Parkinson's disease.

We administered a battery of cognitive tests to 41 recently diagnosed Parkinson patients and 41 controls to assess the early neuropsychological changes associated with Parkinson's disease (PD). Parkinson subjects did as well as controls on tasks assessing attention and select language and visuospatial measures. However, PD subjects did significantly worse on embedded figures, facial recognition, proverbs, and verbal and figural memory measures, and made more perseverative responses on a set shifting task. A discriminant function of measures of proverbs, embedded figures, and memory accounted for 22% of the variance between groups. These data suggest that the cognitive changes in early PD are more pervasive than originally described and may reflect the onset of a more widespread pathologic process.

Cognition Disorders↗

PubMed1989

Glucose-induced sympathetic activation in obesity-prone and resistant rats.

Half of the 3-month-old male Sprague-Dawley rats fed a diet enriched in calories, sucrose and fat (CM diet) for 3 months developed diet-induced obesity (DIO) while the remainder were diet resistant (DR), gaining the same amount of weight as chow-fed controls. DIO was associated with basal hyperinsulinemia and 196 percent heavier retroperitoneal fat pads than DR and chow-fed rats. Intravenous glucose infusion (lg/kg) also produced greater insulin release in DIO rats associated with a 25 percent reduction in glucose disposal rates; areas under the insulin curve were 273 and 51 percent higher than chow-fed and DR rats, respectively. DR rats, on the other hand, showed normal glucose disposal rates but increased insulin release to a glucose load (148 percent greater area under the curve than chow-fed rats). Glucose infusion produced activation of the sympathetic nervous system with release of norepinephrine (NE) into the plasma in chow-fed and DIO but not DR rats which had 40-50 percent lower areas under the NE curve. Also, the areas under the NE curve correlated with body weight gain (r = 0.632; P = 0.040) and retroperitoneal fat pad weight (r = 0.707; P = 0.030) in DR and DIO rats suggesting that glucose-induced sympathetic activation was in some way related to an underlying mechanism of body weight regulation in Sprague-Dawley rats.

Animals↗

PubMed1988

Effects of diet and obesity on brain alpha 1- and alpha 2-noradrenergic receptors in the rat.

The chronic feeding of a sweetened condensed milk/corn oil diet (CM diet) to adult male rats produced significant increases in body weight and levels of plasma insulin in 34% of the rats fed this diet with respect to chow-fed controls. Levels of alpha 1-noradrenergic receptor binding were lower (32%) in the hypothalamic ventromedial nucleus (VMN) of only those rats which became obese (DIO rats) with respect to both chow-fed controls and those rats which resisted the development of obesity on the CM diet (DR rats). Also, alpha 1-noradrenergic binding was inversely proportional to body weight gain in the VMN (r = -0.831). alpha 2-Noradrenergic receptors were 30-37% lower in both the DIO and DR rats in the dorsomedial nucleus and dorsal area of the hypothalamus, and the medial dorsal area and nucleus reuniens of the thalamus. The similar decreases in alpha 2-noradrenergic receptors in both the DIO and DR rats in these areas suggested that dietary factors alone were responsible for these changes. There were no significant differences from chow-fed rats for hypothalamic dopamine (D2) or beta-noradrenergic (beta 1- and beta 2-) receptors in either DR or DIO rats. These results indicate that VMN alpha 1-noradrenergic receptors co-vary with body weight and implicate a role for alpha 1-receptors in the VMN in the central neuronal regulation of body weight.

Animals↗

PubMed1988

The role of norepinephrine in adult rat somatosensory (SmI) cortical metabolism and plasticity.

Stimulation of rat facial vibrissae increases glucose utilization in the corresponding barrels (lamina IV) and associated columns in laminae I-VIa of the contralateral first somatosensory (SmI) cortex as assessed autoradiographically by the uptake of [14C]2-deoxy-glucose (2-DG). Chronic deafferentation (2 months) by bilateral vibrissectomy with sparing of the C3 vibrissa (SC3) in adult Sprague-Dawley rats produced no change in the rate of LCGU but led to an increased areal extent of the metabolic representation of the SC3 barrel (39%, P less than 0.001) and column (31%, P less than 0.003) as compared to rats with fully intact vibrissae. In other rats with intact facial vibrissae, 6-hydroxydopamine lesions of the locus coeruleus (LC) depleted ipsilateral cortical norepinephrine (NE) by more than 90% and, 2 months later, led to an 11% and 21% increase in C3 barrel and column metabolic representations, respectively, as compared to the contralateral SmI cortex with intact NE levels (P less than 0.05). When bilateral vibrissectomy was combined with a unilateral LC lesion, the SC3 barrel and column metabolic representation on the LC-intact side enlarged as expected but no enlargement occurred on the NE-depleted side (20% difference; P less than 0.05). Therefore, the effect of NE on the SmI cortex depends on the status of its afferent input. NE inhibits the spread of metabolic activity beyond the activated barrel and column in the intact cortex, but independently modulates plastic enlargement in the partially deafferented SmI cortex.

Afferent Pathways↗

PubMed1988

Parkinson's disease and depression: psychometric properties of the Beck Depression Inventory.

Although the Beck Depression Inventory (BDI) is one of the most frequently employed measures of depression in Parkinson's disease, the somatic items included in the scale raise questions about its ability to differentiate depression from manifestations of the disease. The internal consistency and validity of the BDI as a measure of depression in a sample of 119 Parkinson's disease patients and 76 controls were studied. Results from an item analysis suggested that depression in Parkinson's disease patients is not a somatic artifact. Internal consistency reliability within the Parkinson's disease group was high. The factorial validity of the BDI was confirmed in both Parkinson's disease and control subjects. The results also indicated that Parkinsonian symptoms of depression can be measured separately from symptoms of the disease. These data suggest that the BDI including the somatic items is a reliable and valid measure of depression in Parkinson's disease and control subjects.

Depressive Disorder↗

PubMed1987

Norepinephrine in the interpeduncular nucleus of the rat: normal distribution and the effects of deafferentation.

We used correlative biochemical and histochemical methods to examine (1) the norepinephrine (NE) projection from the paired locus coeruleus (LC) to the midline interpeduncular nucleus (IPN) of the adult rat and (2) the ability of the LC to respond to denervation of their target following removal of noradrenergic afferents (6-hydroxydopamine lesions of the LC) or non-noradrenergic afferents (lesion of the paired fasciculi retroflexi(FR]. Histofluorescence revealed that the NE innervation from the two LC to the IPN is symmetric and overlapping. This projection is confined to rostral, central, and intermediate subnuclei and is absent from lateral and dorsal subnuclei. We found no evidence for homotypic collateral sprouting of undamaged LC neurons into the IPN following unilateral LC lesion. Bilateral LC lesions also did not induce sprouting by NE-containing neurons from other systems (e.g. the superior cervical ganglion or the lateral tegmental group) or from those LC neurons that survived the 6-hydroxydopamine lesion. Histofluorescence following bilateral FR lesions confirmed an earlier observation that apparent hyperinnervation of the IPN by LC afferents is elicited following removal of non-noradrenergic afferents. Measurements of the turnover rate of NE in the IPN of control animals and those that received bilateral FR lesions indicate an increased NE content and increased turnover rate of NE in the IPN of lesioned animals. Taken together these results suggest an increased number of NE terminals and an increase in the activity of tyrosine hydroxylase. No change in NE content or turnover rate was seen in the frontal cortex from these same animals. This is consistent with a target-dependent regulation of heterotypic collateral sprouting.

Animals↗

PubMed1987

Alterations in catecholamine levels and turnover in discrete brain areas after food deprivation.

The present study determined the levels and turnover of norepinephrine (NE), epinephrine (EPI) and dopamine (DA) in discrete brain areas of rats after 48 hr food deprivation. The steady-state levels of NE, EPI and DA in saline-treated food-deprived rats, relative to satiated rats, remained basically unchanged. However, 48 hr deprivation caused a site-selective potentiation, specifically in the hypothalamic paraventricular nucleus, in the depletion of NE after alpha-methyl-p-tyrosine injection (IP, 200 mg/kg), indicating an increase in NE turnover. While changes in EPI turnover could not be demonstrated, an apparent increase in DA turnover was detected in the perifornical lateral hypothalamus and anterior hypothalamic nucleus after deprivation, while decreased DA turnover was seen in the hypothalamic dorsomedial nucleus and caudate nucleus. These results may reflect specific functions of hypothalamic catecholamines in control of food intake.

Animals↗

PubMed1987

Increases in plasma catecholamines during naturally elicited defensive behavior in the cat.

Defensive behavior was evoked in 12 adult cats by the presentation of both interspecific (barking dog) and intraspecific (hypothalamically stimulated cat) stimuli. Each stimulus was presented 3 times. Concomitant activation of the sympatho-adrenal (SA) system was evaluated by radioenzymatic assay of plasma norepinephrine (NE) and epinephrine (E). The somatic and autonomic displays which accompanied defensive behavior were similar between stimuli, consisting of mydriasis, piloerection, growling, hissing and paw strikes. However, the sympatho-adrenal responses associated with interspecific and intraspecific defensive behaviors were different. Interspecific defensive behavior was accompanied by adrenal medullary release of both NE and E, which decreased with successive trials. Intraspecific defensive behavior was initially associated with release of E from the adrenal medulla; the pattern of catecholamine release in successive trials suggested that in later trials NE was released primarily from the sympathetic nerves. Furthermore, increases in plasma NE and E, as well as increases in heart rate and mean arterial blood pressure during the first trial were significantly greater when the behavioral stimulus was a dog. Although aspects of the feline display to threatening stimuli are stereotyped, the data suggest that the sympatho-adrenal response is more specific, and indicates preparation for fighting or escape.

Animals↗

PubMed1987

Glucose, insulin and sympathoadrenal activation.

Selective activation of the two components of the sympatho-adrenal system (SAS) was produced by infusing male Sprague-Dawley rats with glucose or insulin. Intravenous glucose (0.5, 1 or 2 g/kg) raised plasma levels of glucose and insulin associated with a predominant activation of the sympathetic nervous system (SNS) as indicated by increased plasma norepinephrine (NE) levels. Glucose-induced release of NE was still seen in hypoinsulinemic, streptozotocin-treated rats but was absent after ganglionic blockade with chlorisondamine or following mannitol or saline infusions which failed to alter glucose or insulin levels. Insulin-induced (10 or 20 U/kg) hyperinsulinemia with its associated hypoglycemia produced predominant activation of the adrenal medulla producing increased plasma epinephrine (E) levels. But significant SNS activation also occurred with a concomitant increase in NE levels (14-22% of E) which appeared to be primarily from sympathetic nerves since increases still occurred following adrenal demedullectomy. Therefore, changes in plasma glucose levels alone and possibly altered intracellular concentrations or rates of glucose utilization can act as an important determinant of the pattern SAS activation although this may require pathological changes in plasma glucose levels to occur.

Adrenal Medulla↗

PubMed1987

Functional integration of fetal cortical grafts into the afferent pathway of the rat somatosensory cortex (SmI).

The somatosensory area of fetal (E15-16) Sprague-Dawley rat neocortex was implanted into the barrel receptor area of adult first somatosensory cortex (SmI) to determine if it could be integrated into the host vibrissa-cortical pathway. Functional integration was tested 3-6 months later using the 2-deoxyglucose [44,45] (2-dg) method for estimation of glucose utilization. A variety of control grafts (cerebellum in SmI cortex, neocortex outside the host SmI cortex and appropriately placed neocortex in non-stimulated hosts) all had uniform 2-dg uptake (70 +/- 10 mumol/100 g/min) throughout each graft which averaged 42% less than non-stimulated host SmI cortex (121 +/- 6 mumol/100 g/min; p less than 0.001) but was 3-fold greater than white matter (24.8 +/- 3.1 mumol/100 g/min; p less than 0.001). In appropriately placed neocortical grafts, vibrissal stimulation produced 125% greater average 2-dg uptake (157 +/- 19 mumol/100 g/min) than control grafts (p less than 0.01). Such appropriately placed and stimulated neocortical grafts also contained focal areas of increased 2-dg uptake which were 43% greater than average graft uptake. These data suggest that fetal neocortical grafts were functionally integrated into the physiologically relevant afferent pathways of adult host brains.

Afferent Pathways↗

PubMed1987

Locus coeruleus input affects glucose metabolism in activated rat barrel cortex.

Significant depletion (greater than 50%) of neocortical norepinephrine (NE), 2 weeks after unilateral 6-hydroxydopamine lesions of the locus coeruleus, led to a small (8%), ipsilateral decrease in total C3 vibrissa column 14C-2-deoxyglucose uptake, but a larger (24-32%) increase in the areal extent of this uptake into the metabolic representation of both the C3 column and barrel of the rat somatosensory (SmI) cortex during stimulation of the contralateral C3 facial vibrissae. This suggests a predominantly inhibitory role for NE in modulating SmI oxidative metabolism during physiologic stimulation.

Animals↗

PubMed1987

Resistance to diet-induced obesity: food intake, pancreatic sympathetic tone, and insulin.

After 15 wk on a moderately high-calorie high-fat (CM) diet, 43% of 40 3-mo-old male Sprague-Dawley rats developed diet-induced obesity (DIO) (29% more weight gain), whereas 57% of diet-resistant (DR) rats gained no more weight than 20 chow-fed controls. When switched to chow for another 7 wk, DR rats ate 13% less, gained 55% less weight, and had 49% lower food efficiency, whereas DIO rats ate 4% less but had comparable weight gain and efficiency to controls. DIO rats had 29% more carcass lipid (percent of carcass weight). DIO rat retroperitoneal white adipose pads had 65% more cells that were the same size as those in chow-fed pads; DR rat cells were similar to controls. Both DR and DIO rats increased norepinephrine turnover in their interscapular brown adipose pads by greater than 90%. DIO rats also had 40% lower pancreatic turnover; their plasma insulin levels were 327% of controls after 15 wk on the CM diet and 188% after 7 wk on chow. DR levels were the same as controls at both times. Therefore, regulation of caloric intake, pancreatic sympathetic tone, and plasma insulin levels were three important differences between rats that resisted and those that developed DIO on high-energy diets.

Adipose Tissue, Brown↗

PubMed1987

Glucose-induced norepinephrine levels and obesity resistance.

The value of glucose-stimulated sympathetic activation in differentiating rats that would subsequently resist or develop diet-induced obesity (DIO) when chronically fed a high-calorie diet (CM) enriched in fat and sucrose was tested in 3-mo-old male Sprague-Dawley rats. While the rats were on chow the areas under the curve for plasma glucose, insulin, and norepinephrine (NE) levels were measured for 60 min after an intravenous glucose load (1 g/kg). Half of the rats then switched to the CM diet for 14 wk developed DIO with 54% more weight gain and 205% heavier retroperitoneal fat pads; half [diet resistant (DR)] had weight gain and pad weights comparable to chow-fed controls. Caloric intake was comparable in all animals. NE areas after intravenous glucose loads were 54% lower in DR than DIO rats, and there was a positive correlation (r = 0.63) between these NE areas and subsequent weight gain on the CM diet. Areas under the insulin curve correlated with subsequent weight gain on chow (r = 0.71) but not the CM diet. These results suggest that rats predisposed to become DR on the CM diet have dampened sympathetic activation after a glucose load, possibly because of heightened end-organ responsiveness to NE.

Adipose Tissue↗

PubMed1987

In vivo biosynthesis of two subunit forms of dopamine beta-hydroxylase in rat brain.

In vivo biosynthesis of the 2 subunit forms of dopamine beta-hydroxylase (DBH) was examined in the rat brain. 35S-methionine was injected into the noradrenergic neurons of the locus coeruleus (LC) using a stereotactic device. Several hours later, newly synthesized 35S-Met-labeled DBH was immunoprecipitated and quantitated. Both Mr = 77,000 (77K) and 73,000 (73K) subunit forms were present in near-equal proportions after 4 hr of labeling, and these were indistinguishable from those isolated from rat PC12 pheochromocytoma cells by electrophoretic mobility. Both forms sedimented with the vesicular subcellular fraction of LC homogenates, and a portion of the 73K form could be released by hypotonic lysis of these vesicles. The 77K form predominated in the first 30 min labeling period, while the 73K form appeared more slowly over the next several hours. By 16 hr, the 73K form comprised about 2/3 of the total 35S-Met-labeled DBH present. Inhibition of protein synthesis with puromycin 30 min after 35S-Met injection into the LC did not prevent the subsequent appearance of the 73K form, suggesting that this subunit form was the product of posttranslational modification of the 77K subunit form in a fashion similar to that seen in PC12 cells. Also, newly synthesized 35S-Met-labeled DBH that underwent axonal transport from the LC to the anterior hypothalamus was predominantly the 73K subunit form. A single injection of the catecholamine-depleting drug reserpine (10 mg/kg, i.p.) produced a 17-fold increase in the relative synthesis of DBH 2 d later without affecting the proportion of its 2 subunit forms.

Animals↗

PubMed1986

Plasma catecholamines associated with hypothalamically-elicited flight behavior.

Hypothalamic sites were selected which elicited flight (escape) behavior in the freely moving cat. Sympatho-adrenal (SA) activation was determined by measuring the levels of norepinephrine (NE) and epinephrine (E) in bilateral adrenolumbar and peripheral venous plasma following stimulation of these 29 hypothalamic sites in 18 anesthetized cats. Heart rate (HR) and mean arterial pressure (MAP) were continuously monitored to permit comparisons between SA and cardiovascular (CV) activation. The most frequent SA response was a bilateral increase in the output of NE and E from the adrenal medulla greater than or equal to 10 ng/min. Increases in MAP during hypothalamic stimulation were significantly correlated with bilateral increases in both adrenal CAs, while increases in HR were significantly correlated with increases in peripheral venous NE. The data suggest that hypothalamic regions which elicit flight behavior overlap with regions that activate the adrenal medullary and CV systems. The SA activation that accompanied hypothalamically-elicited escape is compared to SA activation associated with hypothalamically-elicited affective defense.

Adrenal Medulla↗

PubMed1986

Plasma catecholamines associated with hypothalamically-elicited defense behavior.

Sympatho-adrenal (SA) activation was determined by measuring levels of norepinephrine (NE) and epinephrine (E) in bilateral adrenal venous and peripheral venous plasma of 20 anesthetized cats following stimulation of medial hypothalamic sites. Hypothalamic sites were selected that elicited affective defense behavior in the freely moving cat. Fifty-eight percent of these hypothalamic sites elicited a bilateral increase greater than or equal to 10 ng/min in the output of both adrenal catecholamines (CAs); these increases were greater from the gland ipsilateral to the side of stimulation. Other SA responses included both preferential increases or decreases in either NE or E. Under baseline conditions, an average of 67% of the NE in the peripheral venous plasma was contributed by the sympathetic noradrenergic nerves; hypothalamic stimulation at "defense" sites increased the contribution to 75%. The data suggest that hypothalamic regions that elicit defense behaviour may overlap with regions that activate the adrenal medullary and sympathetic nervous systems.

Adrenal Medulla↗

PubMed1986

The effect of diet and chronic obesity on brain catecholamine turnover in the rat.

Male Sprague-Dawley rats were fed a high calorie, high fat diet for 3 months to produce chronic diet-induced obesity (DIO) in which they gained 70% more weight than chow-fed controls. Thirty-six percent of the rats fed the DIO diet resisted the development of obesity (DR), gaining no more weight than chow-fed controls but serving as a comparison for the effects of the diet alone on the metabolism of brain catecholamines. The major influence of dietary composition was upon norepinephrine (NE) metabolism. Both DIO and DR rats had increased turnover of NE (107-217%) and/or shorter NE half-lives (42-67%) than controls in the hypothalamic paraventricular (PVN) and dorsomedial (DMN) nuclei and the median eminence (ME); dopamine (DA) turnover was similarly accelerated in the PVN. The DR rats alone exhibited decreased NE levels with increased disappearance of NE in frontal cortex and increased disappearance of DA in the ventromedial hypothalamic nucleus (VMH). The major effect of chronic obesity alone was a 31-33% decrease in DMN DA turnover and an 80% decrement in ME DA turnover associated with a 61% decrease in DA levels as compared to chow-fed controls. Therefore, the major effect of a high calorie, high fat diet was a diffuse acceleration of brain NE and DA turnover while chronic obesity led to decreased DA turnover in the DMN and ME.

Animals↗

PubMed1986

Increases in blood flow from the adrenal gland following medial hypothalamic stimulation in the cat.

Medial hypothalamic sites previously shown to elicit either flight or defense were stimulated in the anesthetized cat. The rate of blood flow from the adrenolumbar (AL) vein ipsilateral to the side of stimulation was measured, as well as the adrenal output of norepinephrine and epinephrine (E). Stimulation at nearly 15% of the hypothalamic sites increased ipsilateral AL venous flow more than 20% over baseline rates. These sites also significantly increased heart rate, mean arterial pressure, and output of E from the ipsilateral adrenal gland. These observations suggest that hypothalamic sites where stimulation increased AL venous flow may overlap with regions that selectively mediate the release of E from the adrenal medulla.

Adrenal Glands↗