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At least 19 recordsLinked to original sources

PubMed1976

Acute effects of morphine on regional brain levels of acetylcholine in mice and rats.

Morphine increased levels of acetylcholine in mouse striatum in a dose-dependent manner, the increase occurring at the lowest dose previously found to produce analgesia and coinciding with the time of peak analgesic effect. Naloxone blocked this increase. After repeated injections of high doses of morphine, no effect was seen. The hippocampus was the only other brain region showing an effect, and this after a high dose. In the rat, morphine (30 and 90 mg/kg) increased striatal acetylcholine levels. At these and lower doses (2.5 mg/kg and 10 mg/kg) the ratios in the striatum of levels of acetylcholine to levels of dopamine were significantly increased. Only at the highest dose did morphine increase the levels of dopamine in the striatum and of acetylcholine in the hippocampus. Morphine did not change the levels of dopamine in the striatum and of acetylcholine in the hippocampus. Morphine did not change the levels of norepinephrine in either the hypothalamus or cortex of the rat.

Acetylcholine↗

PubMed1976

Effect of manganese on the levels of DNA, RNA, DNase and RNase in cerebrum, cerebellum and rest of brain regions of rat.

Levles of DNA, RNA, DNase, RNase and manganese in different regions of rat brain were studied after daily administration of manganese chloride (8 mg MnCl2-4H2O/kg intraperitoneally) for a period of 120 days. DNA and RNA contents decreased significantly in cerebrum, cerebellum and rest of the brain regions after manganese treatment. A decrease in the DNase and an increase in the RNase activity was observed in the cerebellum and rest of brain region of the manganese treated animals. The manganese content increased significantly in all the regions of the brain, the maximum concentration being in the rest of brain portion. The presence of excess manganese in brain presumably leads to alterations in the functional activity of lysosomal enzymes. The decrease in the levels of nucleic acids is perhaps a consequence of the degenerating and dead neurones.

Animals↗

PubMedDate not supplied

Regional brain blood flow in the conscious gerbil.

Regional brain blood flow was determined in 23 awake, unparalyzed gerbils with a simplified indicator-fractionation technique. The use of intravenous 14C-butanol, an indicator that is freely diffusible into the brain, eliminated the need for repetitive sampling of arterial and cerebral venous blood and reduced the period of indicator circulation of 10 seconds. Gerbils spontaneously breathing room air (PaCO2 = 32 +/- 1 (SE) mm Hg) had blood flows in whole cerebrum, cerebellum, and brainstem of 102 +/- 4, 93 +/- 5, and 114 +/- 6 ml/100 gm/min respectively. Cerebral blood flow increased linearly with elevations in PaCO2 (r=0.969) and averaged 3.14 +/- 0.17 ml/100gm/min per mm Hg increase in PaCO2. Interpolated cerebral blood flow at a PaCO2 of 40 mm Hg was 127 +/- 2 ml/100 gm/min. This technique is easy and convenient to use, involves no intracranial surgery, requires steady state conditions for only 10 seconds, and minimizes blood loss in small animals. In more discrete brain regions a less volatile indicator is needed.

Animals↗

PubMed2026

Predicted brain-regional gene expression patterns in individuals living with Alzheimer's disease.

Studying brain gene expression in Alzheimer's Disease (AD) remains difficult as postmortem brain is difficult to access, cannot be used to guide donor treatment, may be confounded by environmental factors before and after death, and is difficult to link to early AD states or disease progression. To circumvent these limitations, several studies have tested blood transcriptome biomarkers for AD. However, gene-expression levels in the blood have limited correlation with those in the brain. To evaluate the potential of monitoring Alzheimer's progression with peripheral data, we used transcriptome-imputation to identify brain-region-specific AD-associated gene-expression differences in cohorts with blood-based transcriptome data. This approach provides a high-resolution image of AD-associated molecular differences in the brains of individuals actively living with disease. We analyzed eight AD studies (777 AD cases, 779 cognitively unimpaired controls), imputing transcriptomes in 10 brain regions via the Brain Gene Expression and Network Imputation Engine (BrainGENIE). Hundreds of differentially expressed genes (DEGs) associated with AD were identified in nine brain regions, with anterior cingulate cortex and amygdala showing the most differential expression. AD-associated genes were enriched in pathways such as proteostasis, mitochondrial dysfunction, and immune activation. We observed significant yet moderate concordance between imputed AD-associated changes and those directly measured in the dorsolateral prefrontal cortex and cerebellum. These transcriptomic changes can guide future in vitro studies focused on pathogenesis or be targets of novel therapeutic development. In conclusion, we demonstrated the scope and utility of brain expression imputation from the peripheral transcriptome, laying the groundwork for biomarker discovery and prospective AD studies.

Alzheimer Disease↗

PubMedDate not supplied

Measurement of regional brain glucose utilization in vivo using [2(-14)C] glucose.

A new technique is described for the autoradiographic determination of regional brain glucose metabolism employing 14C labeled glucose as substrate and measurement principles previously described for whole brain. Regional glucose values correlate closely with those reported for the 14C-deoxyglucose technique. The method has the advantages of 1) a much shorter experimental period, 2) a relatively simple mathematical treatment, and 3) the utilization of the actual, fully metabolizable substance itself, glucose, as the label. In addition to normal rats, regional values are reported for 20 individual brain areas of rats in bicuculline induced status epilepticus, rats intoxicated with ammonium and rats anesthetized with pentobarbital sodium or ketamine.

Animals↗

PubMedDate not supplied

The effect of (-)-trans-delta 9-tetrahydrocannabinol on regional brain levels and subcellular distribution of monoamines in the rat.

1. The effect of intravenously injected delta 9-tetrahydrocannabinol (delta 9-THC, 2 mg/kg) on subcellular distribution in the whole brain and the regional brain levels of noradrenaline, dopamine, serotonin and 5-hydroxyindoleacetic acid were determined in the rat. 2. The levels of noradrenaline and dopamine were not altered by delta 9-THC in the hypothalamic, medullary and rest of brain areas, whereas those of serotonin and 5-hydroxyindoleacetic acid were elevated in the medullary and hypothalalmic areas, respectively. 3. delta 9-THC did not alter the levels of these monoamines and the metabolite 10 min after injection; however, there was a shift of dopamine from the bound to the free fraction. On the other hand, there was a shift of 5-hydroxyindoleacetic acid from the free to the bound fraction. 4. After 1 h, there was no difference in the subcellular ratios of noradrenaline, dopamine, serotonin and 5-hydroxyindoleacetic acid were increased. 5. It is suggested that the effects of delta 9-THC may be mediated by modification of the subcellular distribution of dopamine and serotonin.

Animals↗

PubMed2016

Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas.

Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology.

Atlases as Topic↗

PubMed1977

Effect of sodium pentobarbital on the apparent turnover of acetylcholine in different brain regions.

The turnover rate of acetylcholine(ACh)was measured in six different brain regions in the mouse following pulse injection of radioactive choline (Ch) and killing of the animals by microwave irradiation of the head (0.25 s, 5 kW). The time course of the change in 3H-ACh/3H-Ch ratio was linear 0-06 s in all brain regions after administration of 3H-Ch. Plots of the specific radioactivities (SA) of ACh and Ch versus time indicate a precursor-product relationship in all brain regions except the cerebellum both in control and sodium pentobarbital anesthesized animals. The turnover was highest in the striatum (55 nmol-g-1-min-1), while in the cortex and hippocampus this value was approximately half (27 and 21 nmol-g-1-min-1). In the midbrain and medulla oblongata the turnover rates were only 11 and 10 nmol-g-1-min-1. Sodium pentobarbital anesthesia reduced specifically the turnover in the cortex and hippocampus to about 60 to 70 percent.

Acetylcholine↗

PubMed1979

Genetic variability for regional brain gangliosides in five strains of young mice.

The quantitative and qualitative distributions of gangliosides were determined in the cerebrum, cerebellum, and brain stem of five inbred strains (C57BL/6J, DBA/2J, LG/J, C3H/HeJ, BALB/cJ) of mice at 21 days of age. Genetic differences were found among the strains for wet weight, absolute amount of gangliosides per region, and concentration of ganglioside (expressed on bolth a wet and a dry weight basis) in all three regions of the brain. The water content of the various brain regions showed the least amount of genetic variability. Coefficients of genetic determination were used to estimate the magnitude of genetic influence on these traits in each brain region. Significant differences were also found among the five strains for the distribution of certain gangliosides. The DBA strain, which is susceptible to audiogenic seizure at this age, had the highest level of the myelin-enriched ganglioside GM1 in all brain regions. Most of the genetic variation that influences the content and distribution of gangliosides among neurologically normal mice can be considered polygenic. Several possible sources of this genetic variation that may contribute to the differences observed among the strains are discussed.

Age Factors↗

PubMed1975

Tyrosine hydroxylase activity in rat brain regions after chronic treatment with +/--propranolol.

Rats were injected twice daily with +/--propranolol (6 mg kg-1 day-1) for 14 days and killed 16 h after the final injection. Tyrosine hydroxylase activity was measured in both soluble and particle-bound forms in various brain regions. The activity of the soluble enzyme was not significantly altered by propranolol treatment in any of the brain regions studied. The tyrosine hydroxylase activity in the particulate fraction was significantly increased in corpus striatum and unchanged in other brain regions. The propranolol concentrations in the various brain regions in this chronic study were far lower than necessary to produce a significant change in tyrosine hydroxylase activity in acute experiments. It was concluded that chronic propranolol treatment produces a persistent increase in bound tyrosine hydroxylase activity in rat corpus striatum.

Animals↗

PubMed1976

Uptake and binding of [3H]hydrocortisone by various pig brain regions.

The cytosol fraction of septum, hypothalamus, and hippocampus of intact and adrenalectomized pigs possessed greater concentrations of radioactivity than the cytosol fraction of amygdala, pituitary, and cortex after an intraventricular injection of [1,2-3H]hydrocortisone. Nuclear extracts from the same brain regions possessed higher concentrations of radioactivity than nuclear extracts of the other brain regions of intact pigs. Nuclear extracts of amygdala, pituitary and hypothalamus from adrenalectomized pigs exhibited the greatest increase over intact pigs in labeled hormone concentration. When adrenalectomized pigs were administered dexamethasone prior to [3H]hydrocortisone, uptake of label was most depressed in hippocampal cytosol and cuclear extract. Also sensitive to the competitive effects of dexamethasone were septal and pituitary nuclear extracts. In intact pigs, pituitary, hippocampus and cortex exhibited higher ratios of bound to total hormone in the cytososl fraction than the other brain regions. Hippocampal and amygdala cytosol possessed the greater magnitude of increase in the ratio of bound to total hormone in adrenalectomized versus intact pigs. The pituitary, septum, amygdala, and cortex of intact and adrenalectomized pigs possessed a ratio of bound to total hormone in nuclear extract 5-10 times greater than that in hippocampus and hypothalamus. However, the latter two regions exhibited a greater increase in bound: total hormone after administration of labeled hormone to adrenalectomized pigs than nuclear extracts of the other brain regions.

Adrenal Glands↗

PubMed1976

Changes in regional brain acetylcholine levels during drug-induced convulsions.

Acetylcholine (ACh) levels were determined in the brain of rats killed by decapitation or focussed microwave radiation during drug-induced convulsions. During metrazol or strychnine-induced convulsions a diffuse decrease in ACh levels was found in rats killed by decapitation. When the rats were killed by radiation and the brain was only divided into three large regions, strychnine caused no changes in ACh levels; metrazol caused a decrease in the cerebral cortex and lower brainstem. When discrete brain regions were investigated in rats killed by radiation, metrazol-induced convulsions were associated with a decrease in ACh level in all regions dissected and strychnine-induced convulsions with a decrease in the hippocampus and caudate nucleus only. Picrotoxin-induced convulsions were associated with a decrease in ACh level in the cerebral cortex, hippocampus, midbrain and medulla-pons, those induced by bicuculline with an increase in ACh level in the frontal cortex, hippocampus, midbrain and medulla-pons, by dimefline with an increase in the frontal cortex, midbrain and medulla-pons and a decrease in the caudate nucleus. The experiments show that each type of convulsant affects ACh levels in discrete brain regions in a different way.

Acetylcholine↗

PubMed1977

Exerimental head injury in the rat. Part 2: Regional brain energy metabolism in concussive trauma.

A standardized model of acceleration concussion in the rat was used for the study of cerebral energy metabolism during the acute concussive reaction. Impact velocities of 7 and 9 m/sec were used, and the cerebral metabolic state was determined 1, 4, and 15 minutes after the impact. A concussive response could be sustained with a normal energy state in the tissue, but with the more intense reaction to a 9 m/sec impact, energy depletion usually occurred. At 1 minute these changes were most pronounced in the brain-stem regions. At 4 minutes the reactions were more varied but a progression usually occurred during this time, while at 15 minutes restitution was indicated. Hypoxia due to neurogenic pulmonary edema aggravated the state. The findings are compatible with a high metabolic rate during concussion, but progressive changes indicate the rapid appearance of complicating factors, including hypoxemia and probably also ischemia.

Adenine Nucleotides↗

PubMed2025

Transcriptome atlases of rat brain regions and their adaptation to diabetes resolution following gastrectomy in the Goto-Kakizaki rat.

Brain regions drive multiple physiological functions through specific gene expression patterns that adapt to environmental influences, drug treatments and disease conditions. To generate a detailed atlas of the brain transcriptome in the context of diabetes, we carried out RNA sequencing in hypothalamus, hippocampus, brainstem and striatum of the Goto-Kakizaki (GK) rat model of spontaneous type 2 diabetes, which was applied to identify gene transcription adaptation to improved glycemic control following vertical sleeve gastrectomy (VSG) in the GK. Over 19,000 distinct transcripts were detected in the rat brain, including 2794 which were consistently expressed in the four brain regions. Region-specific gene expression was identified in hypothalamus (n = 477), hippocampus (n = 468), brainstem (n = 1173) and striatum (n = 791), resulting in differential regulation of biological processes between regions. Differentially expressed genes between VSG and sham operated rats were only found in the hypothalamus and were predominantly involved in the regulation of endothelium and extracellular matrix. These results provide a detailed atlas of regional gene expression in the diabetic rat brain and suggest that the long term effects of gastrectomy-promoted diabetes remission involve functional changes in the hypothalamus endothelium.

Animals↗

PubMed1979

Brain regional levels of neurotransmitter amines as neurochemical correlates of sex-specific ontogenesis in the rat.

Brain regional levels of three neurotransmitter amines - serotonin (5-HT), norepinephrine (NE), dopamine (DA) - were measured in young rats prior to weaning to determine the extent to which modifications in levels of amines might reflect alterations in the sex steroid hormonal environment during the first postnatal week in the life of the rat. Sex-related levels of DA, NE, and 5-HT were found in some brain regions of the 12-day-old rat. Male midbrain DA exceeded the corresponding female value while female hypothalamic NE levels were greater than those of the male. Levels of 5-HT in the corpus striatum and the midbrain of males were greater than those of the female. Castration of the male on day 1 or testosterone propionate (TP) administration to the newborn female resulted in modifications of levels of midbrain 5-HT which reflected feminization of the castrated males and masculinization of the TP-treated females. Castration on day 1, or diethylstilbestrol given on days 2, 4, and 6, resulted in apparent feminization of NE levels in the hypothalamus of 12-day-old male rats. Thus, it appears that regional levels of hypothalamic NE and midbrain 5-HT in the 12-day-old rat may reflect the course of brain organizational activity which becomes recognizable in the adult as sex-specific behavior.

Animals↗

PubMed1978

Autoradiographic maps of regional brain glucose consumption in resting, awake rats using (14C) 2-deoxyglucose.

The 2-deoxy-D-[14C]-glucose (2-DG) autoradiographic method for determining regional brain glucose consumption has been applied successfully by a number of workers for mapping the alterations of brain glucose consumption which occur in association with experimental alterations of brain functional activity. This paper provides a framework for the interpretation of these and further studies by presenting: (1) the pattern of regional brain glucose consumption in the normal, resting, awake rat; (2) the anatomical identities of brain structures which on autoradiographs appear only as regional variations of optical density. For this purpose, a series of 2-DG autoradiographs of coronal brain sections from an injected animal is compared with adjacent labeled Nissl sections.

Animals↗

PubMed1976

Use of 300-msec microwave irradiation for enzyme inactivation: a study of effects of sodium pentobarbital on acetylcholine concentration in mouse brain regions.

Microwave irradiation of 6 kw at 2450 MHz for 300 msec was sufficient to completely inactivate mouse brain cholinesterase and choline acetyltransferase. After this method of sacrifice, the acetylcholine contents of mouse brain regions, given in nanomoles per gram, were found to be: striatum, 81; medulla-pons, 44; diencephalon-midbrain, 34; hippocampus, 31; cerebral cortex, 26; and cerebellum, 17. Sodium pentobarbital caused a dose-dependent increase in whole brain acetylcholine. A maximal increase of 81% in whole brain was seen at 15 minutes with 80 mg/kg of sodium pentobarbital. The increase in acetylcholine after sodium pentobarbital treatment was not caused by anoxia from respiratory depression or by hypothermia. All brain regions except the cerebellum exhibited an increase in acetylcholine after pentobarbital treatment. Fifteen minutes after treatment, cerebellar acetylcholine was significantly decreased. However, at the time when half of the animals had regained the righting reflex, the unconscious mice showed an increase in cerebellar acetylcholine which was statistically significant as compared to control. The relative accumulation rate of acetylcholine calculated for cerebral cortex and hippocampus was higher than that for striatum although the absolute rate of accumulation of ACh was higher in the striatum. Thus, after sodium pentobarbital treatment, the cerebral cortex and hippocampus exhibit a greater cholinergic response than the striatum.

Acetylcholine↗

PubMed1979

Effects of suckling on serum prolactin levels and catecholamine concentrations and turnover in discrete brain regions.

The effects of suckling on serum prolactin levels and catecholamine concentrations and turnover were examined in several discrete brain regions. Turnover rates were assessed by using the synthesis inhibitor alpha-methyltyrosine (alpha-MT) in combination with microdissection techniques for the removal of individual brain regions and sensitive radioenzymatic assays for norepinephrine (NE) and dopaime (DA). Prolactin secretion was induced by mothers experiencing 6 h of pup removal with subsequent pup replacement. Suckling or the administration of alpha-MT to mothers resulted in a marked increase in circulating titers of prolactin. A decrease in steady-state NE concentrations in the anterior hypothalamus and a decrease in steady-state DA concentrations in the ventromedial nucleus were noted in suckled mothers. The comparison of relative rates of NE depletion after alpha-MT treatment revealed a suckling-induced increase in turnover in the ventromedial nucleus and a suckling-induced decrease in turnover in the anterior hypothalamus. Neither suckling nor alpha-MT treatment produced any changes in NE or DA turnover rates in the arcuate nucleus or median eminence. These findings demonstrate that suckling-induced activation of prolactin results in changes in noradrenergic processes in the ventromedial and anterior hypothalamic nuclei. This suggests an involvement of noradrenergic systems in suckling-induced prolactin release.

Animals↗