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1.
—GABA levels in rat whole brain were compared following three methods of sacrifice: rapid microwave fixation, decapitation into liquid nitrogen, and decapitation at 20°C. Levels were shown to be identical in animals sacrificed by microwave fixation and decapitation into liquid nitrogen. In contrast, rats decapitated at 20°C had 18 per cent higher GABA levels when determined immediately post-mortem and 48 per cent higher levels after 30 min at 20°C. Microwave treatment prevented these post-mortem increases. The increase in GABA after decapitation at 20°C was even greater in hypothalamus than in whole brain. A comparison of 3 GABA extraction methods following microwave fixation demonstrated that sodium acetate was 88 per cent as effective as 80 per cent ethanol and more effective than 0·5 n -perchloric acid in extracting GABA. Fifteen brain regions were dissected from microwave-treated brains and the GABA levels determined.  相似文献   

2.
Changes in GABA content of various brain areas during different stages of picrotoxin-induced seizures and following pretreatment with the anti-convulsants phenobarbital andγ-acetylenic GABA were studied. Picrotoxin (6mg/kg) produced clonic/tonic convulsions associated with a 34% reduction in GABA content of the sensory motor cortex. A reduction of 24% was observed 1 min before the onset of seizure and the reduction in GABA content was reversible 20 min after the convulsion. No significant changes were observed in the cerebellum or spinal cord/medulla oblongata. Pretreatment with phenobarbital (100mg/kg) delayed the onset of convulsion and decreased the mortality rate without causing any change in GABA content at the pre-convulsive, convulsive or post-convulsive stages.γ-Acetylenic GABA (100mg/kg) has elevated GABA levels in different areas of the brain by 2–3-fold after 60 min treatment. This increase was reduced by 44% during the onset of picrotoxin-induced seizures. Picrotoxin convulsion can occur in the presence of normal, reduced or even elevated brain GABA content. The only consistent factor is a one-third reduction in GABA content before the onset of seizure.  相似文献   

3.
Abstract– The GABA content of the spinal cord and of approx 70 discrete rat brain nuclei is measured with a simple rapid semi-automated fluorimetric assay, after prevention of post-mortem effects with 3-mercaptopropionic acid. We found that microwave irradiation produced decreases in the GABA contents of the microdissected zona reticulata of the substantia nigra, indicating that microwave fixation is not suitable to measure GABA levels in microdissected brain nuclei. In approx 70% of the nuclei in the anterior half of the brain the GABA concentration was found to be between 41 and 90nmol GABA/mg protein. The GABA content varied from 11 to 40 nmol GABA/mg protein in the posterior half of the brain. High GABA levels were found in some hypothalamic nuclei, the globus pallidus and eminentia mediana. An extremely high GABA level was found in the zona reticulata of the substantia nigra. GABA is unevenly distributed in the striatum. The highest concentration was found in the caudal part and in the ventral region at any level of the striatum. In the spinal cord the highest concentration of GABA was in the sacral region.  相似文献   

4.
Abstract The glutamate (Glu) terminals in rat neostriatum were removed by a unilateral frontal decortication. One to two weeks later the effects of insulin-induced hypoglycemia on the steady-state levels of amino acids [Glu, glutamine (Gin), aspartate (Asp), γ-aminobutyric acid (GABA), tau-rine] and energy metabolites (glucose, glycogen, α-ketoglu-tarate, pyruvate, lactate, ATP, ADP, AMP, phosphocre-atine) were examined in the intact and decorticated neostriatum from brains frozen in situ. The changes in the metabolite levels were examined during normoglycemia, hypoglycemia with burst-suppression (BS) EEG, after 5 and 30 min of hypoglycemic coma with isoelectric EEG, and 1 h of recovery following 30 min of isoelectric EEG. In normoglycemia Glu decreased and Gin and glycogen increased significantly on the decorticated side. During the BS period no significant differences in the measured compounds were noted between the two sides. After 5 min of isoelectric EEG Glu, Gin, GABA, and ATP levels were significantly lower and Asp higher on the intact than on the decorticated side. No differences between the two sides were found after 30 min of isoelectric EEG. After 1 h of recovery from 30 min of isoelectric EEG Glu, Gin, and glycogen had not reached their control levels. Glu was significantly lower, and Gin and glycogen higher on the decorticated side. The Asp and GABA levels were not significantly different from control levels. The results indicate that the turnover of Glu is higher in the intact than in decorticated neostriatum during profound hypoglycemia.  相似文献   

5.
Mice were injected intramuscularly (2 mmol/kg) with the glia-selective GABA uptake inhibitor 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO) 60 min prior to sacrifice, or with glycine (10 mmol/kg) 45 min before death, or with a combination of both. After decapitation of the animals, the brains were removed and synaptosomes prepared and analyzed for content of GABA, taurine, glutamine, serine, glutamate and aspartate. While no differences as compared with control animals were found for aspartate, serine and glutamine, synaptosomal GABA levels were increased significantly after injections with either THPO or glycine. The individual effects of THPO and glycine were found to be additive. Taurine levels were decreased to a similar extent in animals which had received either THPO alone or THPO in conjunction with glycine. Treatment with THPO and glycine in combination led to a decrease in the synaptosomal glutamate content. The findings are consistent with the previously observed synergistic anticonvulsant actions of THPO and glycine being mediated via the GABA neurotransmitter system.  相似文献   

6.
A highly sensitive electron capture gas chromatographic method was developed for quantitation of γ-hydroxybutyrate (GHB) in tissue. This method involves an improved, extraction and purification procedure and a one-step derivatization of GHB to the methyl ester-O-heptafluorobutyrate. As low as 5 ng of GHB in tissue was accurately quantitated by this method. By means of this improved method, endogenous levels of GHB in several regions of brains obtained post-mortem from patients with Huntington's disease were determined, and compared with brain samples obtained post-mortem from non-neurological controls. The levels of GHB found in the caudate and substantia nigra obtained from Huntington's patients were significantly higher than the GHB levels found in similar regions of brain obtained from a non-neurological control group. The content of GABA in the same choreic and control brain samples was also determined. No significant correlation between changes in GHB and GABA levels was observed although there was a trend towards an inverse relationship. The high level of GHR in Huntington's disease may be related to the decrease in succinate:oxidoreductase (EC 1.3.99.1) activity reported by Stahl & Swanson (1974). In two subjects (one control and one Huntington patient) the zonal distribution of GHB in substantia nigra was also determined. The zona reticulata from choreic brain contained a substantially higher level of GHB, whereas the zona compacta contained an amount similar to the level found in control brain.  相似文献   

7.
The effect of hypoxia on brain gamma-aminobutyric acid levels   总被引:4,自引:3,他引:1  
(1) Animals were exposed to hypoxic environments either by supplying them with breathing mixtures low in oxygen or by exposing them in a decompression chamber to simulated altitude. Both methods of producing hypoxia brought about significant increases in brain GABA levels. (2) Elevated GABA levels occurred in all species tested (mouse, hamster, rat, guinea pig, and rabbit) and reached maximal concentration 60 min after the initiation of breathing the hypoxic mixtures. Extension of the exposure beyond 60 min brought about a gradual decline in GABA level from the maximal value reached. (3) A linear relation was found between the oxygen content of the gas mixture and the elevation of GABA level. For guinea pigs, at least, the critical oxygen content required to prevent elevation of GABA level was 8.1 per cent.  相似文献   

8.
Free amino acids have been studied in the brains of fasted mice (18 h) injected intraperitoneally with a 3 mmol/kg dose of imidazole-4-acetic acid (IMA). Groups of mice were killed by cervical dislocation and their brains were removed before injection or at 5, 15, 30, 60, 90 and 120 min after injection and treated immediately with perchloric acid. Amino acid analyses were performed on the perchlorate extracts. Of the 16 amino acids evaluated quantitatively, only glutamic acid and glutamine showed progressive changes during the period of observation, the glutamic acid falling and glutamine levels rising. Serine and threonine levels were increased significantly above the control values from 30 min after the injection to the end of the experiment. Rectal temperatures (measured with a thermistor probe) after injection of IMA showed a progressive reduction from the control levels throughout the period of observation. An essentially linear correlation was noted between the decreases in body temperature and the differences between the glutamic acid and glutamine values for the first 90 min post-injection. Our data suggest that IMA affects mechanisms of temperature regulation, possibly in the hypothalamus, and that, among other processes, the activities of glutaminase and of serine and threonine dehydratases in brain might be reduced when brain temperatures fall.  相似文献   

9.
The effect of acute alcohol infusion on the established suckling-induced prolactin surge in lactating rats was examined. Dams were implanted with an atrial catheter on Day 6 of lactation and blood sampling was done on Day 10. Following the separation of litters from dams for a 6-hr period, a baseline blood sample was removed via a catheter extension. Pups were weighed and returned to dams. Subsequent blood samples were obtained 10, 30, and 60 min after initiation of suckling. Dams were then infused with alcohol doses of 0, 0.5, 1.0, 2.0, or 2.5 g/kg body wt. Infusion (0.1 ml/min) was completed in approximately 30 min. Additional blood samples were obtained 10 30, 60, and 120 min after the termination of infusion. In a separate group of rats, pups were removed from the dam after the first 60 min of suckling and additional blood samples were obtained 40, 70, 90, and 150 min after removal of pups (corresponding to 10-, 30-, 60-, and 120-min samples for rats infused with various alcohol doses). Alcohol, when administered after the establishement of suckling-induced prolactin surge and resulting in blood alcohol levels equal to or greater than legal human intoxication levels, inhibited prolactin release. However, continued suckling for an extended period (120 min in the present study) overcame this inhibitory effect, even when the blood alcohol level was comparable to (2.0 g/kg group) or greater than (2.5 g/kg group) the human legal intoxication level. Furthermore, in rats with established prolactin surges, the patterns of prolactin decline that followed alcohol administration or pup removal were comparable, indicating that similar mechanism(s) may be involved.  相似文献   

10.
The present investigation examined the effects of pretreatment with 3-O-methyl-d-glucose (3OMG) or 2-deoxy-d-glucose (2DOG) on post-mortem rise in rat brain lactate to evaluate their potential use for minimizing ischemia-induced rise in brain lactate. The results showed that iv administration of either glucose analogue (2 g/kg) at 2.5 min prior to sacrifice significantly attenuated (to 0.61 of control levels) post-mortem brain lactate rise. Pretreating rats with 2-deoxy-d-glucose (2 g/kg) 15 min prior to sacrifice resulted in a greater inhibition (to 0.52 of control) of the post-mortem lactate rise. The effects of these two analogues (3OMG and 2DOG) can be accounted for by their inhibition of brain glucose transport and inhibition of brain glucose metabolism by 2DOG. The present results suggest that intervention with either of these glucose analogues under the proper experimental procedures may minimize the cytopathological consequences of ischemia related to the rise in brain lactate.  相似文献   

11.
The possible existence of endogenous substances other than γ-aminobutyric acid (GABA), that can also bind to rat brain GABA receptors, has been investigated in synaptic membranes derived from whole rat brain, or from cerebral cortex; as well as in isolated synaptic vesicles obtained from cerebral cortex, striatum, hypothalamus, cerebellum and spinal cord and in the superfusion fluid of electrically stimulated brain cortex slices, where a GABA-like substance is released by a calcium-dependent process. The detector used to study the presence of such presumed non-GABA endogenous ligands, were frozen and thawed rat brain synaptic membranes, that had been treated with 0.05% Triton X-100 and thoroughly washed. With this highly sensitive preparation, at least 5 pmol of GABA/ml could be detected. The extracts of the different preparations where these hypothetical ligands were looked for, were analyzed by means of gel filtration on Sephadez G-10, paper chromatography and high voltage electrophoresis. In a very great number of experiments performed, the only endogenous ligand detected was GABA itself.The possible influence of a number of peptides on binding of GABA to its receptor, was also looked for. No significant effect was found for substance P, neurotensin, cholecystokinin octapeptide sulfated, somatostatin, thyrotropin releasing hormone, luteinizing hormone releasing hormone, methionine enkephalin (all 10?5 M), angiotensin II (10?4 M), ACTH (3 × 10?7M), poly-l-lysine (30 μg/ml) or poly-l-glutamate (30 μg/ml).  相似文献   

12.
3-Amino-2-hydroxypropyl phosphorothioate (WR77913), a less toxic phosphorothioate radioprotector than WR2721, has been labeled with 35S. The biodistribution of a radioprotective dose of 800 mg/kg was determined in C3H mice bearing RIF-1 tumors as a function of time after intraperitoneal injection and was expressed as percentage injected dose/gram (% ID/g). Levels of 35S in the blood peaked 10 min after injection, and radioactivity in most tissues was highest at 15 min. Label in most tissues declined markedly between 15 and 60 min, but in gut, salivary glands, tumor, and brain, the levels of radioactivity remained quite stable over 1 hr. At 30 min after injection the highest levels of labeled drug were found in submandibular salivary glands, gut, and kidney, with the lowest level in brain. Tumors had approximately the same amount of label as blood, muscle, skin, and esophagus. Two principal differences between the distribution of label from WR77913 and WR2721 were defined. Although blood levels of 35S-WR2721 also peaked 10 min after injection, the 10-min blood levels achieved for WR77913 were more than fourfold greater than those attained by WR2721. Maximum levels of WR2721 occurred in most tissues 30 to 60 min after administration of the drug, compared to 15 min for WR77913. The basis for these differences remains to be determined, but these results suggest that the optimum interval between administration of WR77913 and irradiation may be shorter than for WR2721.  相似文献   

13.
Abstract— The appearance of γ-[3H]hydroxybutyric acid ([3H]GHB) in rat brain at various times after the intraventricular administration of [3H]GABA was determined. Radioactivity recovered as [3H]GHB was maximal 30 s after [3H]GABA administration and declined exponentially thereafter. From a linear transformation of the disappearance with time of [3H]GHB formed from [3H]GABA, the fractional rate of disappearance and turnover time of GHB were calculated. Administration of amino-oxyacetic acid (50 mg/kg i.p.) 1 h before [3H]GABA, reduced [3H]GHB formation, measured 4 min after [3H]GABA, to 28% of that found in control animals. This strongly suggests that GABA-transaminase catalyzes at least one step in the conversion pathway. [3H]GHB recoverable 4 min after [3H]GABA was unchanged when animals were pretreated with pyrazole (1.25–5.0 mmol/kg), diphenyl-hydantoin (25 and 75 mg/kg), phenobarbital (7.5–60 mg/kg), ethanol (1.25–5.0 g/kg), or morphine (2.5–10 mg/kg). Significantly more [3H]GHB could be recovered at several time points from animals which had been pretreated with 50 mg/kg i.p. of the convulsant 3-mercaptopropionic acid.  相似文献   

14.
The technique of estimating gamma-aminobutyric acid (GABA) turnover by inhibiting its major degrading enzyme GABA-T (4-aminobutyrate:2-oxoglutarate aminotransferase; EC 2.6.1.19) and measuring GABA accumulation has been used repeatedly, but, at least in rats, its usefulness has been limited by several difficulties, including marked differences in the degree of GABA-T inhibition in different brain regions after systemic injection of GABA-T inhibitors. In an attempt to improve this type of approach for measuring GABA turnover, the time course of GABA-T inhibition and accumulation of GABA in 12 regions of rat brain has been studied after systemic administration of aminooxyacetic acid (AOAA), injected at various doses and with different routes of administration. A total and rapidly occurring inhibition of GABA-T in all regions was obtained with intraperitoneal injection of 100 mg/kg AOAA, whereas after lower doses, marked regional differences in the degree of GABA-T inhibition were found, thus leading to underestimation of GABA synthesis rates, e.g., in substantia nigra. The activity of the GABA-synthesizing enzyme GAD (L-glutamate-1-decarboxylase; EC 4.1.1.15) was not reduced significantly at any time after intraperitoneal injection of AOAA, except for a small decrease in olfactory bulbs. Even the highest dose of AOAA tested (100 mg/kg) was not associated with toxicity in rats, but induced motor impairment, which was obviously related to the marked GABA accumulation found with this dose. The increase in GABA concentrations induced with intraperitoneal injection of 100 mg/kg AOAA was rapid in onset, allowing one to estimate GABA turnover rates from the initial rate of GABA accumulation, i.e., during the first 30 min after AOAA injection. GABA turnover rates thus determined were correlated in a highly significant fashion with the GAD activities determined in brain regions, with highest turnover rates measured in substantia nigra, hypothalamus, olfactory bulb, and tectum. Pretreatment of rats with diazepam, 5 mg/kg i.p., 5-30 min prior to AOAA, reduced the AOAA-induced GABA accumulation in all 12 regions examined, most probably as a result of potentiation of postsynaptic GABA function. The data indicate that AOAA is a valuable tool for regional GABA turnover studies in rats, provided the GABA-T inhibitor is administered in sufficiently high doses to obtain complete inhibition of GABA degradation.  相似文献   

15.
The endogenous γ-aminobutyric acid (GABA) content of the rat pineal gland and superior cervical ganglion (SCG) was measured by high pressure liquid chromatography. It was found that GABA levels in both tissues increased after decapitation of the animals. The GABA content of tissues frozen within 20 seconds after decapitation was the same as that of tissues removed from animals killed by microwave irradiation. Amino-oxyacetic acid, a GABA-transaminase inhibitor, increased the endogenous GABA content of both of these tissues. Dimethylphenylpiperizinium or isoniazid administration did not alter GABA levels in these tissues. Isoproterenol increased the GABA content of the SCG but did not change the pineal gland GABA levels. The ability of the pineal gland to take up and accumulate 3H-GABA was significantly reduced in rats that had been ganglionectomized. A fluctuation in endogenous GABA levels in the pineal gland was seen to occur when measures were taken at different times of the day. These results tend to suggest that GABA may have some functional role in the pineal gland and the superior cervical ganglion.  相似文献   

16.
It was found that 4-aminobutyraldehyde (ABAL) is a precursor convertible to gamma-aminobutyric acid (GABA) in vivo. [2,3-3H]ABAL was synthesized from [2,3-3H]putrescine. After the subcutaneous administration of [3H]ABAL at the dose of 1 mumol/g body weight, [3H]GABA was produced in the mouse brain in an amount of about 350 nmol/g brain in 10 min. After oral administration of [3H]ABAL at the dose of 2 mumol/g body weight, [3H]GABA was also produced in the brain in an amount of about 530 nmol/g brain in 30 min. It seems that peripherally administered ABAL penetrates the blood-brain barrier into the central nervous system and is rapidly metabolized to GABA in the brain.  相似文献   

17.
—Fructose levels were determined in plasma and brain of 8- to 12-day-old mice at intervals after the injection of 30 mmol/kg intraperitoneally; controls received NaCl, 15 mmol/kg. In normal animals brain fructose increased very slowly despite a rapid rise in plasma levels (120 times the control value in 5 min). At 40 min the cerebral level was 1.54 ± 0.23 mmol/kg; the corresponding plasma level was 47.1 ± 4.8 mM. The data suggest that fructose can serve as a source of energy to the brain in times of critical need: during insulin hypoglycemia brain fructose increased to only 0.88 ± 0.05 mmol/kg during the same interval (40 min) despite plasma fructose values equal to those in control animals; also 30 s after cerebral ischemia (decapitation) brain fructose fell from a zero time value of 1.19 ± 0.09 mmol/kg (20 min after fructose injection) to 0.76 ± 0.06 mmol/kg (P= 0.005). Under both circumstances (hypoglycemia and ischemie anoxia) an apparent threshold concentration of fructose for utilization was observed—0.6–0.7 mmol/kg. The most likely explanation for this finding appears to be that this level of fructose was in the extracellular space of the brain. Hexokinase activity in brain homogenates of 8- to 12-day-old mice with fructose and ATP at concentrations found in vivo and during ischemie anoxia did not appear to be rate-limiting. We concluded that the major handicap to the use of fructose by the brain was the limited penetration of fructose from the blood to the brain.  相似文献   

18.
This study was performed to determine whether minoxidil sulfate (MS), a selective Adenosine 5′-triphosphate-sensitive potassium channel (K ATP channel) activator, has an effect on the expression of caveolin-1 in the rat’s brain tumor tissue. Using a rat brain glioma (C6) model, we found that the expression of caveolin-1 protein at tumor sites was greatly increased after intracarotid infusion of MS at a dose of 30 μg/kg/min for 15, 30, and 60 min via Western blot analysis. And the peak value of the caveolin-1 expression was observed in rats with glioma after 15 min of MS perfusion, which was significantly attenuated by reactive oxygen species (ROS) scavenger (N-2-mercaptopropionyl glycine, MPG). In addition, MPG also significantly inhibited the increase of blood–brain tumor barrier (BTB) permeability which was induced by MS. This led to the conclusion that the MS-induced BTB permeability increase may be related to the accelerated formation of caveolin-1 protein, and could be mediated by ROS.  相似文献   

19.
EFFECT OF γ-AMINOBUTYRIC ACID ON BRAIN SEROTONIN AND CATECHOLAMINES   总被引:1,自引:0,他引:1  
—Intraperitoneal injections of GABA (5 mg/kg) to rats lowered the level of norepinephrine in brain, heart and spleen but not suprarenals and raised that of serotonin in brain. Changes of these monoamines were most pronounced in the hypothalamic region after 20min. A reduction of hypothalamic norepinephrine was also observed 15min following the intracarotid administration of 0·5 mg/kg of GABA. In these experiments there was a concomitant increase in the level of free GABA in the anterior portion of the ventral hypothalamus. Brain dopamine level and 5-hydroxytryptophan decarboxylase, dihydroxyphenylalanine decarboxylase and monoamine oxidase activities were not affected. The 20 per cent increase of endogenous GABA observed in the midbrain 30 min following the administration of amino-oxyacetic acid was accompanied by a sharp fall in norepinephrine level (39 per cent) and an increase in serotonin (20 per cent). In in vitro studies 10–300 μg/ml of GABA were shown to release norepinephrine from cortical and hypothalamic slices, and to inhibit serotonin release without affecting 5-hydroxytryptophan uptake and to have no effect on the release of dopamine from slices of the region of the corpus striatum nor on the activity of the enzymes mentioned. Subcellular studies showed that the particulate:supernatant ratio for norepinephrine was reduced from a control value of 2·04 to 1·75 and that of serotonin was raised from 2·8 to 3·5. Following pretreatment with iproniazid, GABA reduced the raised level of brain norepinephrine to a greater extent than reserpine but not as intensively as amphetamine. The results obtained suggest that these monoamines may be involved in the mechanisms underlying the action of GABA in brain and that the effect of GABA on brain monoamines may be of certain significance in synaptic events.  相似文献   

20.
Abstract— Regional changes in the concentration of GABA and pyridoxal phosphate were determined in rat brain after i.p. administration of convulsant doses of methyldithiocarbazinate (11 mg/kg), isonicotinic acid hydrazide (250 mg/kg) and thiosemicarbazide (25 mg/kg). At 15 and 30 min after methyldithiocarbazinate GABA concentrations were reduced in all brain regions (except ventral mid-brain). After 30 min the largest decrease was in the cerebellum (41%) and the smallest decrease in the hypothalamus (20%). Pyridoxal phosphate concentrations were decreased by 39-57%. After isonicotinic acid hydrazide. the regional decreases in GABA concentration were smaller and of slower onset than those seen after methyldithiocarbazinate. The pons-medulla was the first region to show a decrease (at 15 min) whereas a decrease was not seen in the frontal cortex until 45 min. Regional decreases in pyridoxal phosphate were smaller than those seen after methyldithiocarbazinate. After thiosemicarbazide, small regional decreases in GABA concentration were observed only in the hypothalamus, cerebellum, pons-medulla and posterior cortex (13-18%) and there was no apparent correlation between regional decreases in pyridoxal phosphate and regional decreases in GABA.  相似文献   

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