Local cerebral glucose utilization in the hippocampus of old rats

The local cerebral glucose utilization (LCGU) was measured in the different areas and layers of the Ammon's horn and dentate gyrus of young adult (3 to 4-month-old) rats, and of 27-month-old rats with proven cognitive deficits. The LCGU was determined by quantitative [14C]2-deoxyglucose autoradiography. Compared to young animals, in the old rats the LCGU was significantly reduced by 12% to 15% in the oriens layers of CA1 and CA2, the pyramidal layers of the CA sectors 1-3, the radiatum and lacunosum-molecular layers of CA2 and CA3 and in the lucidum layer of CA3. The LCGU values of all the other layers of the Ammon's horn and the dentate gyrus did not differ significantly between young and old rats. The pattern of the LCGU reduction found in the old rats roughly resembles changes found after fimbra-fornix lesions or systemic administration of scopolamine, suggesting a functionally important deficit in the cholinergic innervation of the old rats' hippocampi.     

Local cerebral glucose utilization in the brain of old,learning impaired rats

Summary The local cerebral glucose utilization (LCGU) was measured in 63 different cortical areas and nuclei of the telencephalon, diencephalon and rhombencephalon of young adult (3 to 4-month-old) rats and of 27-month-old Wistar rats, in which learning impairments had been proven by a water maze test. The LCGU was determined by [¹⁴C]2-deoxyglucose autoradiography. In the old rats the mean LCGU of all brain regions was significantly reduced by about 10% compared with the young control group; the mean LCGU was 74.2 mol glucose/(100 g × min) in the young and 66.7 in the old rats. Different degrees of LCGU decrease were found in the different regions. Most of the brain regions with significantly reduced LCGU values in the aged, learning impaired rats were associated with auditory and visual functions, the dopaminergic system, and structures known to be involved in learning and memory processes. Therefore, the regional pattern of LCGU reduction found in the aged, learning impaired rats did not resemble any known pattern found after lesions of a single transmitter system or systemic administration of transmitter agonists or antagonists.     

Local cerebral glucose utilization in the brain of old, learning impaired rats

The local cerebral glucose utilization (LCGU) was measured in 63 different cortical areas and nuclei of the telencephalon, diencephalon and rhombencephalon of young adult (3 to 4-month-old) rats and of 27-month-old Wistar rats, in which learning impairments had been proven by a water maze test. The LCGU was determined by [14C]2-deoxyglucose autoradiography. In the old rats the mean LCGU of all brain regions was significantly reduced by about 10% compared with the young control group; the mean LCGU was 74.2 mumol glucose/(100 g x min) in the young and 66.7 in the old rats. Different degrees of LCGU decrease were found in the different regions. Most of the brain regions with significantly reduced LCGU values in the aged, learning impaired rats were associated with auditory and visual functions, the dopaminergic system, and structures known to be involved in learning and memory processes. Therefore, the regional pattern of LCGU reduction found in the aged, learning impaired rats did not resemble any known pattern found after lesions of a single transmitter system or systemic administration of transmitter agonists or antagonists.     

Local cerebral glucose utilization in the Ammon's horn and dentate gyrus of the rat brain

The local cerebral glucose utilization (LCGU) was measured in different regions and layers of the Ammon's horn and dentate gyrus in the conscious rat. The LCGU was determined by quantitative [14C]2-deoxyglucose autoradiography using a computerized image processing system. In the hippocampus, the various regions and layers exhibited different glucose consumptions, the lowest values being found in the alveus and the highest ones in the lacunosum-molecular layers of the sectors of the Ammon's horn and the molecular layer of the dentate gyrus' external limb. Additionally, in many layers, the LCGU values of the left hemispheres were found to be higher compared with the right hemispheres. The analysis of LCGU changes in rostrocaudal direction revealed, that in sector 1 of Ammon's horn and in the dentate gyrus the glucose consumption decreased from rostral to caudal levels, whereas in sector 3 of Ammon's horn an increase was found.     

Local cerebral glucose utilization in the Ammon's horn and dentate gyrus of the rat brain

Summary The local cerebral glucose utilization (LCGU) was measured in different regions and layers of the Ammon's horn and dentate gyrus in the conscious rat. The LCGU was determined by quantitative [14C]2-deoxyglucose autoradiography using a computerized image processing system.In the hippocampus, the various regions and layers exhibited different glucose consumptions, the lowest values being found in the alveus and the highest ones in the lacunosum-molecular layers of the dentate gyrus' external limb. Additionally, in many layers, the LCGU values of the left hemispheres were found to be higher compared with the right hemispheres. The analysis of LCGU changes in rostrocaudal direction revealed, that in sector 1 of Ammon's horn and in the dentate gyrus the glucose consumption decreased from rostral to caudal levels, whereas in sector 3 of Ammon's horn an increase was found.Dedicated to Professor Dr. T.H. Schiebler on the occasion of his 65th birthday     

Local cerebral glucose utilization in the autoimmune New Zealand Black (NZB) mouse

Summary By means of the [¹⁴C]-2-deoxyglucose method the local cerebral glucose utilization (LCGU) was measured in 41 brain regions in autoimmune New Zealand Black (NZB) mice and in Carworth Farm Winkelmann (CFW) mice, which served as the control strain. At the age of 6 months, the mean LCGU of all measured areas and brain stem nuclei was 67.7 mol glucose/(100 g x min) in the nonautoimmune CFW mice. These LCGU values are within the limits published by other observers. In contrast, in the aged-matched NZB mice the glucose use was markedly reduced, the mean LCGU of all measured areas being 37.7 mol glucose/(100 g x min). These findings suggest that the immunological, morphological and behavioural abnormalities in the aged NZB mouse correlate with a reduced functional activity of the central nervous system, measured as reduced cerebral glucose utilization.     

Local cerebral glucose utilization in the autoimmune New Zealand black (NZB) mouse

By means of the [14C]-2-deoxyglucose method the local cerebral glucose utilization (LCGU) was measured in 41 brain regions in autoimmune New Zealand Black (NZB) mice and in Carworth Farm Winkelmann (CFW) mice, which served as the control strain. At the age of 6 months, the mean LCGU of all measured areas and brain stem nuclei was 67.7 mumol glucose/(100 g x min) in the nonautoimmune CFW mice. These LCGU values are within the limits published by other observers. In contrast, in the aged-matched NZB mice the glucose use was markedly reduced, the mean LCGU of all measured areas being 37.7 mumol glucose/(100 g x min). These findings suggest that the immunological, morphological and behavioural abnormalities in the aged NZB mouse correlate with a reduced functional activity of the central nervous system, measured as reduced cerebral glucose utilization.     

Local cerebral tissue glucose utilization in graded arterial hemorrhagic hypotension, studied by the 14C-2-deoxyglucose method in rats.

The effect of hemorrhagic arterial hypotension on local cerebral glucose metabolism was studied on 33 rats. The mean arterial pressure was set with the aid of a reservoir at 80, 60, 50 and 40 mmHg pressures. Local cerebral glucose utilization was measured with the 14C-2-D-deoxyglucose accumulation autoradiographic technique. Local glucose consumption decreased somewhat in cortical structures when mean arterial pressure was reduced to 60-50 mmHg. Further decrease in mean arterial pressure to 50-40 mmHg caused inhomogeneity of tissue metabolism. Columns and patches of high glucose consumption interchanged with areas of very low glucose consumption in most telencephalic and cerebellar gray matter structures. Brain stem and white matter structures seem to be less sensitive to decreased mean arterial pressure in the range studied. We found a decrease in glucose utilization rather than an increase with decreasing mean arterial pressure down to 60-50 mmHg (in the range of the autoregulation of cerebral circulation). This finding makes it improbable that autoregulation would be connected with elevated anaerobic metabolism of the tissue. Patchy areas and columns of high glucose consumption found at 50-40 mmHg in all probability reflect areas of increased anaerobic metabolism of glucose. Here, circulation was not enough to transport adequate quantity of oxygen to the tissue, but still it transported relative large amount of glucose. Columns and patches of very low glucose consumption should reflect areas, where circulation was inadequate to transport both enough glucose and oxygen.     

Effects of intra-VTA injection of neurotensin on local cerebral glucose utilization in freely moving rats

The [14C]2-deoxyglucose method was applied to measure the effects of the injection of neurotensin (7 microg) in the ventral tegmental area on local cerebral glucose utilization in the rat. Injection of neurotensin produced significant increases of glucose utilization in the shell of the nucleus accumbens and in the olfactory tubercle. These results indicate that stimulation of neurotensin receptors in the ventral tegmental area produces functional changes that are confined to the regions receiving mesolimbic projections within the rostral extended amygdaloid complex. These findings extend our understanding on the effects of neurotensin in the limbic system, with particular regard to reward pathways.     

Local and global cerebral blood flow and glucose utilization in the α-galactosidase A knockout mouse model of Fabry disease

Fabry disease is an X-linked lysosomal disorder characterized by deficient alpha-galactosidase A activity and intracellular accumulations of glycosphingolipids, mainly globotriaosylceramide (Gb3). Clinically, patients occasionally present CNS dysfunction. To examine the pathophysiology underlying brain dysfunction, we examined glucose utilization (CMR(glc)) and cerebral blood flow (CBF) globally and locally in 18 brain structures in the alpha-galactosidase A gene knockout mouse. Global CMR(glc) was statistically significantly reduced by 22% in Fabry mice (p < 0.01). All 18 structures showed decreases in local CMR(glc) ranging from 14% to 33%. The decreases in all structures of the diencephalon, caudate-putamen, brain stem, and cerebellar cortex were statistically significant (p < 0.05). Global cerebral blood flow (CBF) and local CBF measured in the same 18 structures were lower in Fabry mice than in control mice, but none statistically significantly. Histological examination of brain revealed no cerebral infarcts but abundant Gb3 deposits in the walls of the cerebral vessels with neuronal deposits localized to the medulla oblongata. These results indicate an impairment in cerebral energy metabolism in the Fabry mice, but one not necessarily due to circulatory insufficiency.     

ABRA在正常成年大鼠大脑皮质和海马区的表达

目的观察ABRA(Actin binding Rho activator)在成年大鼠大脑皮质和海马中的表达。方法制备成年大鼠脑的冰冻切片,采用共聚焦免疫荧光技术和免疫荧光强度测量检测ABRA在大鼠大脑皮质和海马区的表达。结果 ABRA在神经元的胞核、胞浆、突起内可见,其中胞核着色最强。在大脑皮质,ABRA阳性的神经元胞体和突起广泛分布于皮质的分子层、外颗粒层、外锥体细胞层、内颗粒层、内锥体细胞层、多形细胞层,其免疫荧光强度分别为129.22±16.94、125.39±29.83、117.67±22.50、105.85±17.65、103.90±18.00、100.23±20.38,ABRA阳性细胞率分别为0.51±0.01、0.69±0.02、0.64±0.03、0.58±0.05、0.65±0.09、0.63±0.01。在海马,ABRA均匀分布于海马各部,阳性神经元集中于锥体细胞层,而其阳性突起弥散分布于海马分子层和多形层。海马锥体细胞层、分子层、多形层免疫荧光强度分别为141.19±35.48、53.19±10.38、43.32±9.59,ABRA阳性细胞率分别为0.62±0.04、0.27±0.07、0.25±0.03。结论 ABRA广泛表达于大鼠大脑皮质和海马各层,提示ABRA可能在大鼠这些部位的神经细胞功能活动方面起重要作用。     

The determination of the local cerebral glucose utilization with the 2-deoxyglucose method

Summary In the adult mammalian brain, the energy metabolism is almost entirely dependent on glucose. Furthermore, a close relationship between the energy metabolism and the functional activity could be shown. Thus, the functional activity of the brain or parts thereof can be quantified by measuring the cerebral metabolic rate for glucose. Studying in vivo the fate of a radioactive labeled analogue of glucose, the 2-deoxy-d-[1-¹⁴C]glucose, and using quantitative autoradiographic techniques, it is possible to estimate the cerebral glucose utilization of every discrete brain region. The advantage of the 2-deoxyglucose method is, that the local cerebral glucose utilization represents a metabolic encephalography (Sokoloff 1982).     

The role of adipose tissue in glucose utilization in irradiated rats

The authors studied the conversion of U-14C-glucose to total lipids, fatty acids and glyceride glycerol in the epididymal adipose tissue of rats X-irradiated with a single whole body dose of 14.4 Gy X-rays. Analyses were carried out 1, 24, 48 and 72 h after irradiation. In the adipose tissue of irradiated rats, the incorporation of 14C-glucose into all the lipid fractions was raised throughout the whole time of observation (300-600% of the control value). Most of the 14C-glucose was incorporated into the glyceride glycerol fraction.     

Increasing protein at the expense of carbohydrate in the diet down-regulates glucose utilization as glucose sparing effect in rats

High protein (HP) diet could serve as a good strategy against obesity, provoking the changes in energy metabolic pathways. However, those modifications differ during a dietary adaptation. To better understand the mechanisms involved in effect of high protein diet (HP) on limiting adiposity in rats we studied in parallel the gene expression of enzymes involved in protein and energy metabolism and the profiles of nutrients oxidation. Eighty male Wistar rats were fed a normal protein diet (NP, 14% of protein) for one week, then either maintained on NP diet or assigned to a HP diet (50% of protein) for 1, 3, 6 and 14 days. mRNA levels of genes involved in carbohydrate and lipid metabolism were measured in liver, adipose tissues, kidney and muscles by real time PCR. Energy expenditure (EE) and substrate oxidation were measured by indirect calorimetry. Liver glycogen and plasma glucose and hormones were assayed. In liver, HP feeding 1) decreased mRNA encoding glycolysis enzymes (GK, L-PK) and lipogenesis enzymes(ACC, FAS), 2) increased mRNA encoding gluconeogenesis enzymes (PEPCK), 3) first lowered, then restored mRNA encoding glycogen synthesis enzyme (GS), 4) did not change mRNA encoding β-oxidation enzymes (CPT1, ACOX1, βHAD). Few changes were seen in other organs. In parallel, indirect calorimetry confirmed that following HP feeding, glucose oxidation was reduced and fat oxidation was stable, except during the 1(st) day of adaptation where lipid oxidation was increased. Finally, this study showed that plasma insulin was lowered and hepatic glucose uptake was decreased. Taken together, these results demonstrate that following HP feeding, CHO utilization was increased above the increase in carbohydrate intake while lipogenesis was decreased thus giving a potential explanation for the fat lowering effect of HP diets.     

Regional cerebral glucose utilization in withdrawal following systemic and intracerebroventricular sufentanil administration

Regional cerebral glucose utilization (RCGU) and behavior were studied during naloxone-precipitated withdrawal in rats after chronic intravenous (IV) or intracerebroventricular (ICV) administration of sufentanil citrate, a potent, highly selective mu opiate agonist. Changes in RCGU were indistinguishable between the two groups (p<0.05) in 21 of 24 anatomically related limbic and brainstem structures known to be activated during withdrawal. Rats made dependent by ICV infusions of sufentanil had smaller RCGU changes in the lateral septal areas, lateral habenular nuclei and paratenial nuclei than rats made dependent by IV infusions of sufentanil. These observations are consistent with infusion artifact, given the proximity of these structures to the site of IVC infusion. All 24 structures had increased RCGU in experimental groups compared with controls (p<0.05). Although linear regression analysis suggests slightly greater RCGU changes in rats after IV sufentanil than in rats after ICV sufentanil (m=0.81), the changes in corresponding structures are highly correlated (r=0.96) indicating qualitatively almost identical RCGU changes. Behavioral changes paralleled RCGU changes and revealed slightly greater withdrawal in rats after IV sufentanil but no clear qualitative differences. Taken together, these results suggest that cerebral metabolic changes in withdrawal following chronic sufentanil administration result exclusively from effects at CNS opiate receptors and not from peripheral receptors. Additionally, the current study provides a model for the production of opiate dependence, by the ICV administration of a specific mu opiate receptor agonist that is relatively free of infusion artifact.