Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Use of 300-msec microwave irradiation for enzyme inactivation: a study of effects of sodium pentobarbital on acetylcholine concentration in mouse brain regions. 0 94

The effects of hypothermia (4 degrees C) on the components of the cholinergic system of the ileal longitudinal muscle and the adherent Auerbach's plexus of the guinea pig ileum have been investigated. Acetylcholine (ACh) content of the muscle was determined by pyrolysis-gas chromatography. It decreased from 119 to a fairly steady level of 16 nmol/g of wet tissue during the first 72 h of cold storage at 4 degrees C under anoxic conditions. Concomitantly, responsiveness to intramural electrical stimulation decreased by 72%. Cholinesterase (ChE) and choline acetyltransferase (ChA) activities each dropped by 40% during this period. However, the de novo synthesis of ACh over the period of study did not change significantly. The response of the preparation to the exogenously applied ACh remained fairly constant suggesting that the changes in the cholinergic receptor are not accountable for the decrease in responsiveness to intramural stimulation. From the results of this study, it has been concluded that cold storage for 5 days leads to: (1) a significant decline in ACh content within 72 h of storage; (2) a decrease in ChE and ChA activities; (3) no significant effect on the cholinergic receptor; and (4) a decrease in responsiveness to intramural electrical stimulation which is probably due to a malfunction of the ACh-releasing mechanism.
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PMID:Effects of cooling on the levels of acetylcholine, cholinesterase, choline acetyltransferase and the intramural electrical stimulation on the guinea pig ileum. 62 70

O-sec-butylphenyl methylcarbamate (BPMC), an anticholinesterase carbamate, was injected once (100 mg/kg, s.c.) or repeatedly (50 mg/kg/day for 10 days) into mice. Animals were examined for their behavior and for parameters of cholinergic activity in the forebrain. Mice that received only a single injection exhibited reduced ambulation, hypothermia, and impairment of rotarod performance for up to 3 hr after a single injection. BPMC increased levels of acetylcholine (ACh) in the forebrain for up to 6 hr, and decreased acetylcholinesterase (AChE) activity for up to 24 hr. Both high-affinity choline uptake (HACU) and binding of [3H]quinuclidinyl benzilate (QNB) were reduced 20 min after a single injection without any effect on choline acetyltransferase (ChAT) activity. In behavioral tests conducted 10 min prior to the daily injections, rotarod performance and ambulation were slightly impaired for a few days before and after cessation of injection. Repeated treatment decreased HACU and binding of [3H]QNB for 24 hr after the final injection without any changes in levels of ACh content, AChE activity and ChAT activity. BPMC may reversibly impair cholinergic functions through effects not only on AChE activity but also on HACU and binding of [3H]QNB.
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PMID:Effects of carbamate, BPMC, on the central cholinergic functions and behavior of mice. 258 33

Scopolamine was either continuously infused or injected once daily into C3H mice. Chronic infusion resulted in mice that were supersensitive to the hypothermia and tremor produced by the muscarinic agonist, oxotremorine. Chronic scopolamine infusion did not alter brain acetylcholinesterase (AChE) or choline acetyltransferase (ChAT) activities but it did produce an increase in brain muscarinic receptors, as measured by quinuclidinyl benzilate (QNB) binding. The maximal increase in QNB binding was seen at the 0.2 mg/kg/hr dose. Further increase in dose resulted in a return to control QNB binding in all brain regions studied except cortex. These animals were still supersensitive to oxotremorine, suggesting a dissociation between receptor number and response to agonist. Animals injected once daily for 10 days with 5 mg/kg exhibited an increase in QNB binding while no increase was seen at 20 mg/kg/day. Chronic oxotremorine infusion resulted in tolerance to the hypothermia-producing effects of oxotremorine. This was accompanied by a decrease in brain QNB binding. Coinfusion of scopolamine with oxotremorine blocked both the tolerance development and receptor changes. These experiments demonstrate that chronic scopolamine treatment can elicit an increase in brain muscarinic receptors which is accompanied by supersensitivity to agonists. However, this effect is not clearly dose related, and a strict relationship between receptor number and agonist response does not exist.
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PMID:Chronic scopolamine treatment and brain cholinergic function. 673 17

The development of tolerance to cholinergic agonists such as oxotremorine is a well established phenomenon. The hypothesis that such tolerance may be explained by a decrease in the number of affinity of muscarinic receptors was tested by chronically treating C3H mice with oxotremorine. Chronic treatment was achieved by continuously infusing oxotremorine via an indwelling i.v. catheter. Doses ranged from 0.03 to 1.0 mg/kg/hr. Clear tolerance was observed in that symptoms such as salivation, lacrimation and muscle tremor decreased or disappeared during the infusion period. Similarly, chronically treated animals exhibited minimal hypothermia or impairment of rotarod performance when challenged with an oxotremorine dose which significantly depressed both of these measures in naive animals. The activities of the enzymes, acetylcholinesterase and choline acetyltransferase, as well as the binding of [3H]-3-quinuclidinyl benzilate in seven brain regions, were assessed. Chronic oxotremorine treatment failed to alter acetyltransferase activity in any of the brain regions. Choline acetyltransferase activity was only marginally decreased in several brain regions. A significant decrease in maximal [3H]-3-quinudidinyl binding was observed in six of the regions examined. No alteration in [3H]-3-quinuclidinyl affinity was detected. Tolerance to oxotremorine was detected at doses which failed to alter choline acetyltransferase activity or receptor number. These data support the observations of others who noted that chronic muscarinic stimulation results in a decrease in muscarinic receptors, but suggest the importance of mechanisms other than decreased receptor number in early stages of tolerance development.
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PMID:Cholinergic adaptations to chronic oxotremorine infusion. 725 34

Effect of methylmercury chloride (MMC) on behavior was studied in male ICR-JCL mice. In order to clarify the causal relationship between the potent suppressing action of MMC on the central cholinergic system and toxic manifestations, behavioral changes induced by MMC were compared with those induced by the two reference drugs, hemicholinium-3 (HC-3) and 3'-chloro-4-stilbazole (CS; a potent choline acetyltransferase inhibitor). When administered intraperitoneally, daily in a dose of 5 mg Hg/kg/day, MMC caused a decrease in spontaneous motor activity, rotarod dysfunction, and hypothermia before an abrupt loss in body weight and the appearance of overt signs. These behavioral changes were similar to some extent to those induced by HC-3 or CS. A single intracerebral injection of HC-3 (51 or 100 micrograms/kg) caused hypothermia and rotarod dysfunction over a period of 40-250 min. A single intraperitoneal administration of CS (100 or 200 mg/kg) induced a decrease in spontaneous motor activity, hypothermia, and rotarod dysfunction over a period of 1-5 hours after injection. These results suggest that the prior toxic behavioral changes caused by MMC may be related to suppression of the cholinergic system.
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PMID:Neuropharmacological effect of methylmercury in mice with special reference to the central cholinergic system. 731 Nov 66

The spontaneously hypertensive rat (SHR) is a widely used animal model for essential hypertension, and is less susceptible to cold restraint stress in gastric ulcer formation. We previously reported that acid secretion is low in SHR due to sympathetic facilitation compared with normotensive Wistar-Kyoto rats (WKY). The purpose of this study was to evaluate the autonomic nervous function and the gastric mucosal blood flow related to gastric motility during cold restraint stress in SHR. Male SHR and WKY, 24-28 weeks old, were used in this study. Noradrenergic innervation, noradrenaline and dopamine contents in the muscle layer were significantly greater in SHR than in WKY, and tissue choline acetyltransferase activity was significantly lower in SHR. Gastric motility was markedly enhanced by cold restraint stress in WKY. By contrast, SHR maintained the rhythmic and low amplitude contractions regardless of hypothermia. Mucosal blood flow decreased markedly during hypothermia in WKY but was well sustained in SHR. In conclusion, the increase in gastric motility associated with cold restraint stress was suppressed in SHR by sympathetic facilitation in the muscle layer, and this may have contributed to the prevention of ulcer formation by maintaining mucosal blood flow in SHR.
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PMID:Gastric mucosal blood flow in relation to stress-induced hypercontraction in spontaneously hypertensive rats. 776 May 25

The protective effect of regional epidural spinal cord cooling was evaluated in a rabbit spinal cord ischemia model. Hypothermia was performed by the continual perfusion of 2-4 degrees C cold saline in the epidural space around the ischemic lumbar segments, 4 min before and during ischemia. The spinal cord was deeply hypothermic (21 degrees C) throughout the whole ischemic period. Ischemia was induced by the occlusion of the abdominal aorta for 40 min under normothermic or hypothermic conditions. Recovery of motor and sensory functions, spinal cord-evoked potentials, and motor-evoked potentials were then evaluated up to 24 h postischemia. After this period, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were measured, in particular, zones of the lumbar spinal cord. AChE was also investigated histochemically. Animals in the normothermic group displayed fully developed spastic paraplegia with near complete loss of spinal somatosensory and motor-evoked potentials. AChE histochemistry showed extensive necrotic changes affecting lumbosacral gray matter. These changes corresponding with the pronounced losses of ChAT and AChE activities indicated irreversible injury of the spinal cord. In contrast, after hypothermic ischemia, animals survived without any sign of neurological impairment with almost full recovery of the spinal cord-evoked potentials. ChAT and AChE activities in the gray matter showed near control values corresponding with histochemical analysis of fully preserved gray matter. Hypothermia under the present experimental conditions efficiently protected the spinal cord against ischemic injury.
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PMID:Epidural perfusion cooling protects against spinal cord ischemia in rabbits. An evaluation of cholinergic function. 853 29

Apolipoprotein E-deficient mice provide a useful system for studying the role of apolipoprotein E (apoE) in the function of distinct neuronal systems. In the present study we focused on the cholinergic system of these mice. This was pursued by measurements of specific biochemical, physiological and cognitive parameters. Morris Water Maze tasks revealed impairments in working memory but not in reference memory of the apoE-deficient mice. Measurements of brain choline acetyltransferase activities revealed them to be markedly lower in the hippocampus and frontal cortex of the apoE-deficient mice than in the corresponding brain areas of the controls, but unaltered in other brain areas. In addition, hypothermia induced by the centrally acting muscarinic agonist, oxotremorine, was reduced in the apoE-deficient mice as compared to controls. These results show that apoE-deficient mice have cholinergic deficits and highlight the importance of this mouse model for studying the interactions between apoE and the cholinergic nervous system.
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PMID:Memory deficits and cholinergic impairments in apolipoprotein E-deficient mice. 858 14

ApolipoproteinE (ApoE) genotype has recently been identified as a major risk factor for Alzheimer's disease (AD) but the mechanism(s) by which ApoE isoforms influence this disease remain unclear. Recent studies suggest that mice deficient in ApoE may exhibit impaired central cholinergic function. Since this neurotransmitter system has traditionally been associated with the pathogenesis of AD, we have further investigated the impact of ApoE gene deletion on this system. Female ApoE knockout (ko) mice, age 12 months, were compared with wild type littermate controls using a range of behavioural, biochemical and histochemical techniques. Pre-treatment with the cholinomimetic, donepezil (E2020; 2.5-5 mg kg-1 IP), produced significant hypothermia and induction of tremor in both wild type and ApoE ko mice. The magnitude of change did not significantly differ between the groups. Cognitive testing in the Morris water maze revealed that both wild type and ApoE ko mice could learn the location of a hidden escape platform with similar rates of acquisition and accuracy. Similarly, the behaviour of both genotypes proved indistinguishable in a Y-maze spontaneous alteration procedure. The protocols used for both cognitive tests were then shown to be sensitive to the disruptive effects of scopolamine (but not scopolamine methyl bromide). Following behavioural testing, choline acetyltransferase (ChAT) activity was measured in the hippocampus, frontal and entorhinal cortex and striatum. In each case there was no difference between the genotypes. In addition, coronal sections of striatum and anterior hippocampal regions of ApoE ko and wild type mice showed similar patterns of acetylcholinesterase (AChE) staining, with no qualitative or obvious quantitative difference. Finally, analysis of plasma cholesterol levels confirmed ApoE genotype. In conclusion, using a combination of behavioural, histochemical and biochemical measurements, we have failed to detect any significant differences in central cholinergic activity between wild type and ApoE ko mice.
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PMID:Absence of central cholinergic deficits in ApoE knockout mice. 926 10


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