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Biomedical subjects

B E Levin

Publications and source records attributed to B E Levin.

At least 91 records · Page 5Linked to original sources
PubMed1992

Intracarotid glucose induced norepinephrine response and the development of diet induced obesity.

Intracarotid glucose infusions cause increased plasma norepinephrine (NE) levels in some rats. This is used as an index of sympathetic activation. Similar increases in plasma NE levels are produced by intravenous glucose injections and these levels correlate positively with the amount of weight gained by adult rats when they are subsequently fed a diet enriched in calories, sucrose and fat (condensed milk (CM) diet) for three months. Thus, rats prone to develop diet induced obesity (DIO) on the CM diet have greater intravenous glucose induced NE responses than those which are diet resistant (DR). To test the hypothesis that this relationship is mediated by the brain, 17 chow fed, adult male Sprague-Dawley rats were infused for 60 min with intracarotid glucose at 4 mg/kg/min and blood samples were obtained for plasma catecholamines, insulin and glucose. They were then placed on the CM diet for three months. After three months on the CM diet, there was a wide variability in body weight gain and the weights of retroperitoneal fat pads, an indirect measure of carcass adiposity. For all 17 rats, there was a significant correlation between both body weight gain (r = 0.685, P = 0.002) and retroperitoneal fat pad weights (r = 0.590, P = 0.013) with the levels of plasma NE reached 45-60 min into the preceding intracarotid glucose infusions. For the six lowest and six highest glucose induced NE responders, the correlation between NE response and body weight gain on CM diet was r = 0.944 (P = 0.0001). Plasma epinephrine, insulin and glucose levels were unchanged during such infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

Cognitive impairments in Parkinson's disease.

The clinical neuropsychologic profiles of patients with Parkinson's disease and patients with SDAT show both overlap and dissociation. Speech, language, and certain memory skills are examples of dissociable differences, especially in the early stages of the disease. Furthermore the presence of depression, evidence of cognitive slowing, and absence of aphasia in patients with Parkinson's disease suggest prominent subcortical involvement. It is probably premature to categorize all of the cognitive changes in patients with Parkinson's disease as subcortical, however. Some skills, such as visuospatial and executive functions, are impaired in both disorders, and although the etiologic bases for task failure may differ for each, this issue remains open-ended. Another problem is that often the evidence for or against the cortical/subcortical distinction is insufficient and in some cases based on a single measure thought to be representative of a given cognitive domain. Most importantly there are few comparative studies that provide unequivocal support for making a cortical/subcortical distinction. Failure to equate for level of cognitive impairment or functional disability between dementias and strict adherence to cross-sectional study designs further compromise efforts to characterize each syndrome precisely. Whitehouse suggested that a prospective study of several different dementias studied in parallel, examining a wide range of cognitive skills, is required before the cortical/subcortical classification scheme can be validated. A critical component is an autopsy program to confirm diagnoses and provide clinicopathologic correlation. It is possible that the diverse nature of the cognitive impairment in patients with Parkinson's disease is not a methodologic artifact but reflects multiple disease subtypes. Ross, Mahler, and Cummings proposed three dementia syndromes in patients with Parkinson's disease: one that is relatively mild and meets the criteria for subcortical dementia, a second that is more severe and shows a wider range of cognitive impairment but is still neuropathologically distinct from SDAT, and a third severe dementia with both subcortical and cortical involvement that may reflect basal ganglia and Alzheimer-type pathology.

Cognition Disorders↗
PubMed1991

Fetal neocortical transplants into the medial forebrain bundle attract ingrowth of catecholaminergic fibers in adult rat brain.

The hypothesis that fetal tissue grafts may exert a trophic influence on damaged catecholaminergic fibers was examined. Ascending dopamine and norepinephrine axons normally innervate frontal cortex targets in the intact rat brain. These and other ascending catecholaminergic fibers were disrupted with stereotaxic injections of 6-hydroxydopamine into the medial forebrain bundle (mfb), followed after 1 or 14 days by grafts of fetal neocortical tissue placed into the injection site, or by sham grafts. Glyoxylic acid histofluorescence techniques were then used to examine catecholaminergic fiber distribution. When such lesions were made without subsequent grafting, virtually no growth of catecholaminergic fibers occurred beyond the injection site and frontal cortex norepinephrine levels were depleted to 15% of control levels. However, when grafts of fetal neocortical tissue were made into the lesion site and animals examined 3 months later, catecholaminergic fibers grew through the lesion site to ramify within the graft tissue. Catecholaminergic fibers were seen in all portions of most grafts, though they were most dense on the caudal and ventral edges of the graft, close to the path of the mfb. Similar densities of graft innervation were seen 3 months after animals received grafts placed into the same site without prior lesioning of catecholaminergic fibers. Fetal neocortical grafts thus induce collateral sprouting from intact host catecholaminergic axons and may also promote regenerative sprouting when such fibers are otherwise irreparably damaged.

Animals↗
PubMed1991

Adult rat barrel cortex plasticity occurs at 1 week but not at 1 day after vibrissectomy as demonstrated by the 2-deoxyglucose method.

Stimulation of a single facial vibrissa in rats receiving [14C]2-deoxyglucose leads to increased local cerebral glucose utilization in the corresponding contralateral barrel of lamina IV of the first somatosensory cortex (SmI). In the adult rat, the metabolic representation of such a barrel enlarges 2 months after removal of all other vibrissal follicles but enlargement is prevented by prior removal of SmI norepinephrine. Here, the early time course of such enlargement and how this was affected by cortical norepinephrine manipulations were examined in adult rats. One day after total vibrissal follicle removal with sparing of the central (C3) vibrissa, neither the areal extent nor absolute glucose utilization in the stimulated, spared C3 cortical barrel were changed. However, 7 days after follicle removal, the spared C3 barrel was enlarged by 41%, although absolute glucose utilization remained constant. This delayed onset of enlargement is compatible with either a structural or neurochemical change in barrel circuitry following vibrissal deafferentation. With ipsilateral locus coeruleus lesions but intact vibrissae, there was progressive enlargement of stimulated C3 barrel areas with increasing cortical norepinephrine depletion (r = 0.864) suggesting a suppressive effect of norepinephrine on activity spread in barrels with intact vibrissal afferents. Previously shown blockade of chronic (2 month) vibrissectomy-induced barrel enlargement by norephinephrine depletion suggested an additional effect on plasticity. Even though acute (1 day) follicle removal here produced no change in spared C3 barrel area, addition of norepinephrine depletion produced a surprising 40% decrease in barrel area. Thus, barrel plasticity assessed by 2-deoxyglucose reflects a complex interaction between barrel metabolic activity and the extent of vibrissal and noradrenergic afferent input.

Animals↗
PubMed1991

Spontaneous motor activity during the development and maintenance of diet-induced obesity in the rat.

More than 80% of most daily spontaneous activities (assessed in an Omnitech activity monitor) occurred during the last hour of light and 12 h of the dark phase in 8 chow-fed male Sprague-Dawley rats. Thirty additional rats were, therefore, monitored over this 13-h period to assess the relationship of activity to the development and maintenance of diet-induced obesity (DIO) on a diet high in energy, fat and sucrose (CM diet). Nine of 20 rats became obese after 3 months on the CM diet, with 71% greater weight gain than 10 chow-fed controls. Eleven of 20 rats were diet resistant (DR), gaining the same amount of weight as chow-fed rats. Neither initial activity levels nor initial body weights on chow (Period I) differed significantly across retrospectively identified groups. After 3 months on CM diet or chow (Period II), as well as after an additional 3 months after CM diet-fed rats returned to chow (Period III), there were significant inverse correlations (r = -.606 to -.370) between body weight at the time of testing and various measures of movement in the horizontal plane. There was no relationship to dietary content nor consistent correlations of body weight or diet group to vertical movements, an indirect measure of ingestive behavior. Patterns of time spent in the vertical position were significantly different for DIO vs. DR rats in Period III, however. Thus, differences in food intake and metabolic efficiency, rather than differences in nocturnal activity, are probably responsible for the greater weight gain in DIO-prone rats placed on CM diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Defective cerebral glucose utilization in diet-induced obese rats.

A neural mechanism may underlie the divergent weight gain patterns of rats fed a high-energy diet; half develop diet-induced obesity (DIO), whereas the rest are diet resistant (DR). Male rats were fed chow (n = 14) or a high-energy diet for 3 mo with the development of DIO (n = 11) or DR (n = 12). DIO rats had 159-219% heavier retroperitoneal fat pads and 158% higher plasma insulin levels than chow-fed and DR rats, but plasma glucose levels were equal. Rats were trained to drink glucose after an overnight fast and were tested for local cerebral glucose utilization using 2-deoxy-D-[14C]glucose autoradiography in the presence or absence of 0.15% saccharin substituted for glucose. Saccharin intake increased 2-deoxyglucose uptake in the rostral nucleus tractus solitarius of DR but not DIO or chow-fed rats. Also, DIO rats had reduced basal 2-deoxyglucose uptake in the central amygdaloid nucleus. High-energy diet intake was associated with saccharin-induced depression of 2-deoxyglucose uptake in the inferior olive and increased utilization in the medial amygdaloid nucleus of both DR and DIO rats. Thus DIO rats have diminished basal and food-related neuronal activity in certain brain areas involved in food intake and autonomic function. Furthermore, dietary content affects glucose utilization in areas not usually associated with these functions.

Animals↗
PubMed1991

Glucose increases rat plasma norepinephrine levels by direct action on the brain.

The hypothesis that glucose can selectively activate the sympathetic nervous system (SNS) by direct action on the brain was tested using plasma norepinephrine (NE) and epinephrine (Epi) responses to intracarotid and intravenous glucose injections as indexes of SNS and adrenal medullary responses, respectively. Intracarotid glucose bolus injections (0.1 g/kg) transiently raised plasma glucose (22%) and insulin (98%) levels at 2 min and increased plasma NE, but not Epi, levels from 2 to 60 min. Areas under the NE curve were 700% higher than equiosmolar doses of mannitol. An intravenous glucose bolus (1 g/kg) gave quantitatively similar but delayed (30 min) NE responses to the 0.1 g/kg intracarotid dose but raised plasma glucose 500% and insulin 1,700% above baseline at 2 min postinjection. Slow intracarotid glucose infusions for 60 min at 4 mg.kg-1.min-1 raised plasma NE levels from 30 to 60 min with 250% higher areas under the NE curve than the intracarotid and intravenous bolus doses but without a change in plasma glucose, insulin, or Epi levels. Infusions at 6 mg.kg-1.min-1 transiently raised plasma NE levels at 30 min without altering glucose, insulin, or Epi levels. These results suggest that glucose alone can produce a selective, delayed SNS activation by a direct action on the brain.

Animals↗
PubMed1991

A retrospective analysis of the effects of anticholinergic medication on memory performance in Parkinson's disease.

We examined the effects of anticholinergic medication on memory function in 113 patients with idiopathic Parkinson's disease (PD). Subjects were divided into three disease duration groups: early, middle, and advanced. The battery consisted of three tasks assessing memory of logical discourse, semantically related words, and figural material. We found no evidence of anticholinergic-induced memory dysfunction in any of the three groups. Analysis of covariance indicated that age was not a significant variable; however, dementia may have influenced the relationship between anticholinergic medication and memory scores. Our results indicate that anticholinergic medication does not uniformly compromise memory function in PD patients.

Aged↗
PubMed1991

Visuospatial impairment in Parkinson's disease.

We explored the nature of the visuospatial deficit in Parkinson's disease (PD) and its progression as a function of disease duration. We compared the performance of 183 patients with idiopathic PD and 90 control subjects matched for age and education on six visuospatial measures. We divided patients into three groups according to the disease duration: early (1 to 4 years), middle (5 to 10 years), and advanced (greater than 10 years). Performance deteriorated in five of the six visuospatial measures, as a function of disease duration. However, the pattern of visuospatial decline depended on whether dementia was present. The results were not influenced by age or anticholinergic medication. These findings support the presence of visuospatial deficits in PD patients, with a changing pattern of impairment related to dementia and progression of the disease.

Aging↗
PubMed1990

Obesity-prone and -resistant rats differ in their brain [3H]paraminoclonidine binding.

Half the rats fed a high-energy diet develop diet-induced obesity (DIO); the remainder are diet-resistant (DR). Since alpha-adrenoceptors modulate both food intake and body weight, this study was conducted to identify potential differences in brain alpha-receptor binding which might predispose some animals to become DIO (DIO-prone) and others DR (DR-prone) when fed a high energy diet. DIO-prone rats can be prospectively identified by high and DR-prone rats by a low plasma norepinephrine (NE) response to i.v. glucose. Here 28 chow-fed rats were tested for glucose-induced NE release and the 6 highest and 6 lowest plasma NE responders were identified as being most likely to be DIO- and DR-prone, respectively. Binding to brain alpha-adrenoceptors was studied in these 12 rats by receptor autoradiography using 1 nM [3H]prazosin (PRZ; alpha 1-) and 1 nM [3H]paraminoclonidine (PAC; alpha 2-). There were no differences in [3H]PRZ binding in any of 18 brain areas examined. However, DIO-prone [3H]PAC binding was only 14-39% of DR-prone levels in 9 areas including 4 amygdalar nuclei, the lateral area, dorso- and ventromedial nuclei of the hypothalamus, median eminence and medial dorsal thalamic n. Although it is unclear whether this widespread decrease in [3H]PAC binding implicates brain alpha 2-adrenoceptors in the pathophysiology of DIO, it does correlate with a phenotypic marker (increase glucose-induced NE release) which predicts the subsequent development of DIO on a high-energy diet.

Animals↗
PubMed1990

Are all subcortical dementias alike? Verbal learning and memory in Parkinson's and Huntington's disease patients.

The utility of the concept of 'subcortical dementia' was investigated by comparing the verbal learning and memory abilities of Parkinson's disease (PD) patients with those of Huntington's disease (HD) patients. Many similarities between the PD and HD groups emerged, including impaired immediate memory spans, inconsistency of recall across learning trials, deficient use of a semantic clustering learning strategy, elevated intrusion rates on delayed recall, impaired recognition memory performance, normal retention of information over delay periods, normal vulnerability to proactive or retroactive interference, and normal types of intrusion errors. The HD subjects, however, displayed inferior free recall, deficient improvement across learning trials, abnormal serial position recall effects, higher perseveration rates, and supranormal improvement on recognition testing compared with free recall. Implications of these results for characterizing memory deficits associated with subcortical system dysfunction are discussed.

Adult↗
PubMed1990

Effects of dehydroepiandrosterone treatment in rats with diet-induced obesity.

Previous studies showed that administration of dehydroepiandrosterone (DHEA) to lean and genetically obese Zucker rats reduced body weight. In the present experiments, the effect of DHEA treatment in rats with diet-induced obesity was evaluated. In experiment 1, male Sprague-Dawley rats (300 g) were fed a nonpurified diet (reference group) or a condensed milk-corn oil nonpurified diet [diet-induced obese (DIO) rats] for 7 wk. Then, 0.6% DHEA was included in the food of one-half of the DIO rats (DIO + DHEA rats). After 6 wk, DIO rats weighed 23% more and had greater fat pad weights, cell size and cell number than reference and DIO + DHEA rats. Brown fat mitochondrial respiration was similar in all groups. DIO rats had higher serum cholesterol and triacylglycerol concentrations than reference and DIO + DHEA rats. DIO + DHEA rats had lower serum insulin levels than DIO and reference rats. In experiment 2, male Sprague-Dawley rats (460 g) were fed either the nonpurified diet or the condensed milk diet for 8 wk. Condensed milk-fed rats were then divided into DIO and diet-resistant groups. One-half of the rats in each group were fed 0.6% DHEA for 2 wk. Body weights and serum glucose, insulin, triacylglycerol and triiodothyronine levels were lowered by DHEA treatment in all groups. Liver mitochondrial state 3 respiration rates per gram and per liver and peroxisomal beta-oxidation were higher in DHEA-treated than in control rats. In DIO rats, DHEA treatment appears to interfere with hyperplastic adipose tissue growth. In this strain of rats, DHEA appears to have hypolipidemic and hypoinsulinemic effects.

Adipose Tissue↗
PubMed1990

Spatial cognition in Parkinson disease.

Visuospatial deficits have been found repeatedly in patients with Parkinson disease (PD). However, their precise nature and significance remain controversial. Whereas it is often asserted that primary visuospatial impairments begin early in the disease, others argue that poor performance on visuospatial tasks reflects methodological artifact. This article reviews research on spatial cognition in PD. Five categories of spatial functions are described: visual analysis and synthesis; facial recognition; judgment of direction, orientation, and distance; constructional praxis; and spatial attention. Proposed guidelines for future research include the use of conceptual rather than operational definitions of visual spatial ability, greater attention directed at separating spatial from nonspatial task components, and studies examining basic mechanisms underlying spatial vision.

Aged↗
PubMed1990

Increased brain 3H-paraminoclonidine (alpha 2-adrenoceptor) binding associated with perpetuation of diet-induced obesity in rats.

Brain alpha-adrenoceptor (alpha-AR) binding was examined as a possible explanation for the persistence of diet-induced obesity (DIO) or resistance (DR) in rats after they were returned to chow from a high-energy, fat and sucrose diet (CM diet). Adult Sprague-Dawley rats (n = 28) were fed the CM diet for 12 weeks. Those that gained more weight than chow-fed controls were classified as DIO and those that gained the same weight as controls were called DR. The 10 heaviest DIO and 8 lightest DR rats were then placed on chow for an additional 14 weeks. After the entire 26-week period, the body weights of DIO rats were still 21 per cent greater and those of the DR rats were 9 per cent less than 7 chow-fed controls. DIO retroperitoneal fat pads were also 62 per cent heavier while DR pads were equal to controls. Plasma insulin and glucose levels were comparable in all 3 groups. Receptor autoradiographic studies of brain alpha 1-AR (3H prazosin; PRZ) and alpha 2-AR (3H-paraminoclonidine; PAC) adrenoceptor binding were carried out using these animals at the end of 26 weeks. Binding to alpha 1-AR was comparable in all groups but alpha 2-AR binding was 47-103 per cent higher in DIO compared to DR and chow-fed controls in 14 of 17 brain areas assessed. These included the dorsomedial, ventromedial and paraventricular hypothalamic n. and all amygdalar areas. Such widespread differences in alpha 2-AR binding in rats fed the same diet but of differing body weights suggest that alpha 2-AR binding is a marker for differences in body weight regulation and may be important in the control of the differences in weight gain.

Adrenergic alpha-Agonists↗
PubMed1989

Noradrenergic innervation does not affect chronic regulation of [125I]pindolol receptors in fetal rat brain transplants or host neocortex.

Fetal (E15-16) somatosensory cortex (n = 15) or cerebellum (n = 9) were placed into the somatosensory cortex (SmI) of adult rat hosts to study the relative importance of tissue origin versus host milieu on graft beta-adrenoceptor regulation. Autoradiographic studies of [125I]pindolol ([125I]pin) binding in the presence of 3 microM serotonin were performed as an index of beta-receptor binding in both intact hosts and those with ipsilateral locus coeruleus (LC) lesions and/or ipsilateral superior cervical ganglionectomy. [125I]pin binding within fetal grafts was highly variable with areas of highest specific binding in cortical grafts (Kd = 209 +/- 30 pM, Bmax = 106 +/- 7 (fmol/mg protein) being comparable to host cortex (Kd = 211 +/- 41 pM, Bmax = 111 +/- 9 fmol/mg protein). Average total binding in whole cortical grafts was 73% and in cerebellar grafts was 60% of that in comparable adult cortex. Host cortex had 66-73% and cerebellum had 4-8% beta 1-receptors while cortical grafts had 59% and cerebellar grafts had 43% beta 1-receptors as determined by competitive binding with ICI 89406 and 118551. Noradrenergic fibers derived from both the host LC and superior cervical ganglion grew into fetal cortical grafts. Binding to high affinity uptake sites ([3H]desmethylimipramine, [3H]DMI) on noradrenergic terminals in cerebellar grafts was 28% higher than that in cortical grafts; superior cervical ganglionectomy decreased [3H]DMI binding in cortical grafts by 37% but had no effect on cerebellar grafts. Neither ganglionectomy nor LC lesions affected total specific binding or binding to beta-receptor subtypes in the grafts or host cortex 3-6 months after removal. Therefore, anatomic site of origin appeared to be the predominant factor in determining the development of beta-adrenoceptors in fetal cortical tissue. In ectopically placed cerebellar grafts, beta-receptor subtypes did not develop comparably to host cerebellar receptors suggesting that host milieu may be of critical importance in receptor development in this tissue.

Adrenergic Fibers↗
PubMed1989

Differences in saccharin-induced cerebral glucose utilization between obesity-prone and -resistant rats.

Approximately half the male Sprague-Dawley rats fed a high energy diet develop diet-induced obesity (DIO). The remainder are diet-resistant (DR) and do not become obese. Resistance to DIO can be predicted before exposure to high energy diets by the presence of diminished norepinephrine (NE) release to an intravenous glucose load. Here chow-fed rats were prospectively placed in DR- or DIO-prone 'diet groups' by the areas under their glucose-induced (1 g/kg, i.v.) NE curves (DR rats less than 1200 pg/ml/60 min; DIO rats greater than 4500 pg/ml/60 min). To test the central pathways involved in the response to the intake of palatable foods, rats were first trained to drink 1 ml of 50% glucose within 1 min and then were tested for local cerebral glucose utilization using uptake of [14C]2-deoxy-D-glucose ([14C]2-DG) after receiving 0.15% sodium saccharin in place of glucose to avoid altering plasma glucose levels. Controls for basal cerebral metabolism (C) received no solution. DR-prone rats increased [14C]2-DG uptake by 60-190% in autonomic areas of the medulla (nucleus tractus solitarius, area postrema, dorsal motor nucleus X) and amygdala (central nucleus) in the S versus C conditions while DIO-prone rats had high basal levels of [14C]2-DG uptake in these areas and showed no increase after S. Also, DR-prone rats had 9-25% higher [14C]2-DG uptake in the ventromedial hypothalamic nucleus than DIO rats regardless of C or S conditions. Thus, pre-existing differences in the activation of autonomic areas of the brain in response to a food-related cue may be of etiological significance in the different patterns of food intake and weight gain seen in DR- and DIO-prone rats fed a high energy diet.

Animals↗
PubMed1989

Initiation and perpetuation of obesity and obesity resistance in rats.

A search was made for predisposing factors and sequelae of diet-induced obesity (DIO) or resistance to DIO (DR). During 3 mo on a high-energy (CM) diet, two-thirds of the male Sprague-Dawley rats ate 16% more calories over the first 30 days and developed DIO. The remaining one-third were DR, gaining the same amount of weight as chow-fed controls. Basal and norepinephrine (NE)-stimulated in vivo O2 consumption, performed before rats were placed on the CM diet, was the same in those rats that later became DR or DIO after 3 mo on the CM diet. DR rats were 4% lighter, whereas DIO rats were equal to chow-fed rats before their exposure to the CM diet. When CM-fed rats were switched to chow, DIO rats took 14 wk to reduce their body and retroperitoneal fat pad weights to those of chow-fed controls, whereas DR rats gained only 40% of the body weight, and fat pads were 34% lighter than controls. After 14 wk, DIO rats were neither hyperinsulinemic nor insulin resistant, whereas DR rats had 64% reduced areas under their insulin curves after intravenous glucose (1 g/kg) compared with controls. Unlike younger rats, animals here had inconsistent plasma NE responses to intravenous glucose. Therefore the CM diet produces DR and DIO states that tend to become self-perpetuating once established.

Animals↗