Organophosphate-mediated inhibition of choline acetyltransferase activity in rat brain tissue

Summary Administration of the organophosphate compound soman in rats resulted in an inhibition of choline acetyltransferase activity in almost all brain regions examined. Enzyme activity was inhibited by 20–50% in various brain regions 30 min after soman injection (94–120 g/kg). Enzyme activity in two regions decreased with time to a near zero level by 3 h after injection.Research sponsored by the Air Force Office of Scientific Research/AFSC, United States Air Force, under Contract F49620-82-C-0035. This work was also supported by PHS MBRS Grant No. RR08037. The cooperation of Dr G. Goddard of the School of Aerospace Medicine, Brooks AFB, is gratefully acknowledged.     

Adrenocortical metabolism and plasma corticosterone in soman intoxicated rabbits

The organophosphate neurotoxin soman produced impairments in adrenocortical RNA and protein metabolism. Fasciculate and reticular cell RNA and protein contents were suppressed with sublethal to acutely lethal dosages (20, 30 and 40 micrograms/kg, s.c.) during the acute excitatory phase of intoxication and at 6-8 h post injection. All three dosages produced ca 90% inactivation of plasma cholinesterase. A transient elevation of plasma corticosterone occurred with 20 micrograms/kg soman whereas there was a protracted increase with 30 micrograms/kg. Corticosterone was not significantly elevated with 40 micrograms/kg, but death occurred at 13 +/- 4 min. Thus, the magnitude and/or nature of soman-induced metabolic impairments does not appear to prevent adrenal activation.     

Angiotensin I converting enzyme activity in pulmonary tissue of fetal and newborn rabbits

Summary Angiotensin I converting enzyme in pulmonary tissue of fetal and newborn rabbits was measured using Hip-His-Leu as substrate. Enzyme activity was detected in the late fetal period, increased gradually until birth and increased markedly after birth. Enzyme activity reached adult levels on the 2nd and 3rd day after birth. This observations suggests that the metabolic activity of the lung for angiotensin develops suddenly at the time of derivery.This work was supported in part by grant No. 187032 from Ministry of Education.     

Versuche zur chemischen GedächtnisÜbertragung von farbdressierten Goldfischen auf undressierte Tiere

Summary 36–48 h after the i.p. injection of a low molecular brain extract prepared from colour-trained goldfishes into naive goldfish, these recipients show positive reactions comparable to those shown by the donors. 12–24 h after the injection, the recipients showed an increased activity. No changes in behaviour have been noticed in the recipients of i.p. injections of low molecular brain material from untrained donor fish.     

In vivo inactivation of transglutaminase during the acute acrylamide toxic syndrome in the rat

The activity of liver and brain transglutaminase is rapidly lost following i.p. injection of acrylamide (50-200 mg/kg). Other enzymes investigated were not modified by the treatment, with the exception of brain enolase.     

Monoamine oxidase activity of the brain of Locusta migratoria in normal conditions and after intoxication by two insecticides: chlordimeform and dieldrin]

Our investigations have shown up an MAO activity in locust brain, by the use of a radio-isotopic method, as much at larval as at adult stage. This MAO activity is in a sample of 34,3 dpm/mg of brain tissue (wet weight). Investigations have also been undertaken on effects of dieldrin and chlordimeform poisoning on this MAO activity. Even at sublethal dosages, chlordimeform causes a significant inhibition of MAO activity in vivo. This finding is in accordance with Beeman and Matsumura's work in vitro. Moreover, acute poisoning by dieldrin produces more than 60% of inhibition of MAO, 3 hours after administration of 115 microng of this insecticide by injection in the hoemocelian cavity.     

Effect of diabetes on the enzymes of the cholinergic system of the rat brain

Summary Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were determined in several brain regions of normal and streptozotocin-induced diabetic rats. The diabetic rats exhibited significant increase in ChAT activity (p<0.05) in all brain regions studied except for the cortex and the midbrain. Meanwhile, the diabetes condition was associated with significant increase (p<0.05) in AChE activity of the bulbus olfactorius, medulla oblongata and cerebellum. These data suggest that uncontrolled diabetes is associated with significant alterations in the brain cholinergic systems.To whom requests of reprints should be addressed.This work was supported by grants from the National Aeronautics and Space Administration (NSG 2183 and NAG-2-411), a grant from the National Institutes of Health (NIH Grant RR0811) and a grant from the Division of Research Resources, National Institutes of Health (NIH Grant RR03020).     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4°C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4°C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.This work was supported by a grant from the National Aeronautics and Space Administration (NSG 2183 and NAG 2-411), a grant from the National Institutes of Health (NIH RR 0811) and a grant from the Division of Research Resources (NIH grant RR 03020).     

Inactivation of sarin and soman by cyclodextrins in vitro

Cyclodextrins catalyzed the inactivation of sarin and soman but did not inactivate tabun and VX. Furthermore, sarin and soman showed greater affinity for beta-cyclodextrin than for alpha- or gamma-cyclodextrins. Thus beta-cyclodextrin appears to be an attractive starting material for the preparation of a catalyst able to inactivate sarin and soman more effectively. Such a catalyst might contribute to improving the therapy of poisoning caused by these two nerve agents.     

Neural discharge can be modulated by carotid arterial injection of gastrin-17 in rat hypothalamic paraventricular nucleus

Neural discharge in the hypothalamic paraventricular nucleus (PVN) was examined after gastrin-17 injection into the carotid artery in anesthetized rats. Neural discharge was increased by gastrin-17 injection into the carotid artery close to the cranium, and the response due to the gastrin was dose-dependent. No discharge response was seen when gastrin was injected into the jugular vein. These results suggest that gastrin circulating in the arterial blood can penetrate the blood brain barrier, and modulate neural PVN activity which is responsible for gastric acid secretion.     

DNA fragmentation in leukocytes following subacute lowdose nerve agent exposure

The objective of the present study was to determine levels of DNA fragmentation in blood leukocytes from guinea pigs by single-cell gel electrophoresis (comet assay) after exposure to the chemical warfare nerve agent (CWNA), soman, at doses ranging from 0.1 LD₅₀ to 0.4 LD₅₀, once per day for either 5 or 10 days. Post-exposure recovery periods ranged from 0 to 17 days. Leukocytes were imaged from each animal, and the images analyzed by computer. Data obtained for exposure to soman demonstrated significant increases in DNA fragmentation in circulating leukocytes in CWNA-treated guinea pigs compared with saline-injected control animals at all doses and time points examined. Notably, significantly increased DNA fragmentation was observed in leukocytes 17 days after cessation of soman exposure. Our findings demonstrate that leukocyte DNA fragmentation assays may provide a sensitive biomarker for low-dose CWNA exposure.Received 29 July 2003; accepted 14 August 2003     

Inactivation of sarin and soman by cyclodextrins in vitro

Summary Cyclodextrins catalyzed the inactivation of sarin and soman but did not inactivate tabun and VX. Furthermore, sarin and soman showed greater affinity for -cyclodextrin than for - or -cyclodextrins. Thus -cyclodextrin appears to be an attractive starting material for the preparation of a catalyst able to inactivate sarin and soman more effectively. Such a catalyst might contribute to improving the therapy of poisoning caused by these two nerve agents.     

Adrenocortical metabolism and plasma corticosterone in soman intoxicated rabbits

Summary The organophosphate neurotoxin soman produced impairments in adrenocortical RNA and protein metabolism. Fasciculate and reticular cell RNA and protein contents were supporessed with sublethal to acutely lethal dosages (20, 30 and 40 g/kg, s.c.) during the acute excitatory phase of intoxication and at 6–8 h post injection. All three dosages produced ca 90% inactivation of plasma cholinesterase. A transient elevation of plasma corticosterone occurred with 20 g/kg soman whereas there was a protracted increase with 30 g/kg. Corticosterone was not significantly elevated with 40 g/kg, but death occurred at 13±4 min. Thus, the magnitude and/or nature of soman-induced metabolic impairments does not appear to prevent adrenal activation.Supported by US Army Medical Research and Development Command Contract DAMD 17-81-C-1202.     

Galactosyltransferase of Neurospora

Summary An enzyme, galactosyltransferase, able to catalyze the formation of galactose polymers was detected in cell-free extracts of a wild type strain of Neurospora crassa. Enzyme activity was found in both the supernatant and the particle fractions after centrifugation at 100,000 xg. The enzyme assayed in the 100,000 xg supernatant showed a 4fold difference in specific activity as compared to that found in the particle fraction.Acknowledgment. This work was supported by a grant from the Research Corporation.     

Physiological studies on the effects of nutritional imbalance on the central nervous system. II. Effects of thiamine deficiency on oxidative enzymes in the brain of chicken,Gallus domesticus

Summary The activity levels of succinate dehydrogenase, glutamate dehydrogenase and pyruvate dehydrogenase in the fore, mid and hind brain regions of the thiamine deficient chicken,Gallus domesticus were determined. The activity levels of scccinate dehydrogenase and glutamate dehydrogenase in all the 3 regions of brain showed augmentation on inducing thiamine deficiency. In contrast the activity levels of pyruvate dehydrogenase decreased in the brain of thiamine deficient animals. It is suggested that these changes in the oxidative enzymes indicate disturbance caused in the operation of the tricarboxylic acid cycle in thiamine deficiency.     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat.

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4 degrees C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4 degrees C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.     

In vivo inactivation of transglutaminase during the acute acrylamide toxic syndrome in the rat

Summary The activity of liver and brain transglutaminase is rapidly lost following i.p. injection of acrylamide (50–200 mg/kg). Other enzymes investigated were not modified by the treatment, with the exception of brain enolase.     

Effect of diabetes on the enzymes of the cholinergic system of the rat brain

Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were determined in several brain regions of normal and streptozotocin-induced diabetic rats. The diabetic rats exhibited significant increase in ChAT activity (p less than 0.05) in all brain regions studied except for the cortex and the midbrain. Meanwhile, the diabetes condition was associated with significant increase (p less than 0.05) in AChE activity of the bulbus olfactorius, medulla oblongata and cerebellum. These data suggest that uncontrolled diabetes is associated with significant alterations in the brain cholinergic systems.     

Physiological studies on the effects of nutritional imbalance on the central nervous system. II. Effects of thiamine deficiency on oxidative enzymes in the brain of chicken, Gallus domesticus.

The activitiy levels of succinate dehydrogenase, glutamate dehydrogenase and pyruvate dehydrogenase in the fore, mid and hind brain regions of the thiamine deficient chicken, Gallus domesticus were determined. The activity levels of succinate dehydrogenase and glutamate dehydrogenase in all the 3 regions of brain showed augmentation on inducing thiamine deficiency. In contrast the activity levels of pyruvate dehydrogenase decreased in the brain of thiamine deficient animals. It is suggested that these changes in the oxidative enzymes indicate disturbance caused in the operation of the tricarboxylic acid cycle in thiamine deficiency.     

Galactosyltransferase of Neurospora.

An enzyme, galactosyltransferase, able to catalyze the formation of galactose polymers was detected in cell-free extracts of a wild type strain of Neurospora crassa. Enzyme activity was found in both the supernatant and the particle fractions after centrifugation at 100,000 X g. The enzyme assayed in the 100,000 X g supernatant showed a 4fold difference in specific activity as compared to that found in the particle fraction.