Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The exact cellular origin and the degree of collateralization of the major efferent projections from the internal segment of globus pallidus (GPi) in squirrel monkey (Saimiri sciureus) were studied using Evans blue (EB) and a mixture of DAPI-primuline (DP) as retrograde fluorescent tracers. After the concomitant injection of EB in VA/VL thalamic nuclei and of DP in habenula on the same side, numerous EB-labeled cells were found in the central portion of GPi compared to a much smaller number of DP-labeled neurons mostly encountered at the periphery of GPi. Only very few double-labeled cells were visualized in these experiments indicating that the pallidohabenular and pallidothalamic pathways arise largely from two different cell populations, each having a preferential distribution in GPi. On the other hand, a multitude of both EB- and DP-labeled cells occurred in the central portion of GPi after the concomitant injection of EB in VA/VL nuclei and of DP in nucleus tegmenti pedunculopontinus of the midbrain tegmentum. Although the EB-labeled cells tend to be more abundant in the dorsolateral half, and the DP-labeled cells more numerous in the ventromedial half of GPi, about 70-75% of the cells in the core of GPi were double-labeled in such a case. This indicates that the pallidothalamic and pallidotegmental fibers arise largely from the same neurons in the core of GPi. A number of DP-labeled cells was also found in the contralateral GPi revealing that the pallidotegmental pathway is partly (15-20%) crossed. In addition, numerous DP-labeled cells (projecting to brain stem) occurred in the medial two-thirds of the substantia nigra pars reticulata (SNr), whereas EB-labeled cells (projecting to the thalamus) abounded in the lateral third of SNr. A small number of double-labeled SNr cells were also encountered after thalamus-midbrain injection. These findings suggest that in regard to its output elements, the primate GPi is organized according to a complex pattern consisting of: (1) a central 'motor' zone where most neurons send axonal branches to both thalamus and midbrain; and (2) a peripheral 'limbic' zone which encroaches largely upon the lateral hypothalamus and whose cells project only to habenula. These two pallidal zones are furthermore embedded in a peripallidal neuronal network composed of large acetylcholinesterase-containing cells related to nucleus basalis and projecting diffusely to neocortex.
...
PMID:Organization of efferent projections from the internal segment of globus pallidus in primate as revealed by fluorescence retrograde labeling method. 712 69

Subcutaneous injection of a sublethal dose of chlorpyrifos (CHLP), an organophosphate (OP) pesticide, causes long-term inhibition in cholinesterase activity (ChE) of brain, blood, and other tissues. Such prolonged inhibition in ChE should lead to marked behavioral and autonomic thermoregulatory patterns, especially in terms of altered noradrenergic and cholinergic sensitivity. To evaluate the behavioral and autonomic effects of long-term ChE inhibition, Long-Evans rats were implanted with radiotelemetry transmitters that continuously monitored core temperature (Tc), heart rate (HR), and motor activity (MA). These parameters were monitored for 7 days following a single injection of peanut oil (vehicle control) or 280 mg/kg CHLP. CHLP led to a significant reduction in Tc during the first night after treatment but had no other effects on Tc. CHLP also resulted in a significant elevation in HR which lasted for approximately 72 h. Motor activity was unaffected by CHLP. Cholinergic and noradrenergic drug sensitivity was assessed between 7 and 25 days after CHLP. CHLP-treated rats were more sensitive to norepinephrine as based on a greater hyperthermic response. MA of CHLP-treated rats was more sensitive to scopolamine. On the other hand, the hypothermic effects of oxotremorine (0.4 mg/kg) were nearly abolished by CHLP treatment, indicating tolerance to cholinergic stimulation. The tachycardic effects of methyscopolamine were also greater in the CHLP group. Overall, the acute effects of CHLP are unusual compared to other OP's in that there is no hypothermic response, an attenuated nocturnal elevation in Tc and a prolonged elevation in HR.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Thermoregulatory effects of chlorpyrifos in the rat: long-term changes in cholinergic and noradrenergic sensitivity. 751 60

When given to rats, O,O'-diethyl-O-[3,5,6-trichloro-2-pyridyl]- phosphorothionate (chlorpyrifos), a common insecticide, causes an unusually lengthy dose-dependent fall in the activity of brain acetylcholinesterase (AChE; EC 3.1.1.7). To determine whether the slow recovery involves impaired AChE synthesis, experiments were designed to measure AChE activity, immunoreactive AChE protein (AChE-IR) and AChE mRNA. Male, Long-Evans rats, maintained at 350 +/- 5 g, were dosed (s.c.) weekly for 4 weeks with 0, 15, 30, or 60 mg/kg chlorpyrifos in peanut oil. Brain tissue was harvested 1, 3, 5, 7 and 9 weeks after treatment began. AChE activity was measured by Ellman assay, and AChE-IR was estimated by two-site ELISA using monoclonal antibodies to rat brain AChE. While AChE activity fell significantly at all times and doses, AChE-IR increased at 3 and 5 weeks in the two higher dosage groups. Larger increases of AChE-IR were observed after chlorpyrifos was administered for 4 weeks by the oral route. Northern blots quantified with reference to cyclophilin were consistent with stable levels of AChE mRNA. Overall, it appears that chronically reduced brain AChE activity after chlorpyrifos reflects sustained enzyme inhibition, not loss of enzyme protein or suppression of AChE message.
...
PMID:Slow accumulation of acetylcholinesterase in rat brain during enzyme inhibition by repeated dosing with chlorpyrifos. 753 66

Rat lines were selected by breeding for sensitivity to signs of autonomic stimulation (hypotherma, loss of body weight, and reduced water intake) induced by the cholinesterase inhibitor diisopropyl fluorophosphate (DFP). These lines have since been maintained for 10 generations by continued selection for hypothermic responsiveness to the muscarinic agonist oxotremorine. The sensitive rats (Flinders Sensitive Line, FSL) differ from the resistant rats (Flinders Resistant Line, FRL) both neurochemically and behaviorally, particularly in aversively motivated test situations in which response speed is assessed. This study was conducted to determine whether the selected differences in cholinergic autonomic sensitivity would be expressed as differences in cognitive ability based on choice accuracy in appetitive tasks. The working and reference memory of rats of these two strains was thus assessed using operant delayed matching-to-position/visual discrimination (DMTP/VD) and the radial-arm maze. A Long-Evans (L-E) reference group was included in the DMTP/VD study. FSL rats responded more slowly than the other rats during acquisition of both tasks, but showed no differences in response accuracy either during acquisition or during asymptotic performance of either task. In addition, challenges with muscarinic and nicotinic antagonists and agonists [scopolamine (0.06-1.0 mg/kg), pilocarpine (1.0-4.0 mg/kg), mecamylamine (1.0-10.0 mg/kg), and nicotine (0.1-0.3 mg/kg)] demonstrated predicted differences in sensitivity among the lines only on performance measures such as response latency and trial completion. Counter to prediction, the sensitivity of the FRL rats to the ability of scopolamine to reduce matching accuracy was lower than those of the L-E and FSL rats. Thus selection based upon physiological endpoints related to cholinergic autonomic homeostasis did not produce analogous differences in cognitive function in rats.
...
PMID:Spatial working and reference memory in rats bred for autonomic sensitivity to cholinergic stimulation: acquisition, accuracy, speed, and effects of cholinergic drugs. 766 85

This study examined whether the expression of behavioral effects of grafts rich in cholinergic neurons placed into the hippocampus of rats with septohippocampal damage may be modulated by postoperative housing or training conditions. Among 91 Long-Evans female rats, 61 sustained a bilateral aspirative lesion of the fimbria-fornix fibers and all overlying tissue, while 30 were given sham operations. Ten days after surgery, fetal septal suspension grafts were performed in the hippocampus of half the lesioned rats. Two days later, all rats were randomly assigned to one of three housing or training conditions: standard, standard with daily training, and enriched. Two and 5 months later, the rats were tested for learning using a Hebb-Williams maze. At both these delays, performance was clearly impaired in lesioned rats and was found to be ameliorated by grafts only in rats which had received daily training. Cresyl violet staining and acetylcholinesterase histochemistry showed that, irrespective of the housing or training conditions, all grafts had survived and provided the denervated hippocampus with a substantial cholinergic reinnervation. Our results suggest that the beneficial behavioral effects of intrahippocampal suspension grafts of septal cells may depend on the postsurgical training or handling conditions of the graft recipients. This result might be of importance for interpreting some behavioral effects of grafts, since in most studies in which grafts were found to induce beneficial behavioral effects (especially on learning capacity), these effects were generally observed at the end of a rather long testing period. Moreover, the present findings show that this delay, before graft function is expressed, might be linked not only to the time needed by grafts to establish a functional reinnervation in the host brain, but also to the training and/or handling conditions of the graft recipient.
...
PMID:The effects of intrahippocampal grafts, training, and postoperative housing on behavioral recovery after septohippocampal damage in the rat. 766 89

The preponderance of studies of tolerance to organophosphate (OP) cholinesterase (ChE) inhibitors indicates that functional recovery accompanies neurochemical compensations for the inhibited enzyme. Contrary to prediction, rats dosed with the OP diisopropylfluorophosphate (DFP) showed progressive and persistent impairment of cognitive and motor function over a 3-week period of daily exposure, despite neurochemical and pharmacological evidence of tolerance to its inhibition of ChE. To determine whether these functional effects of DFP resulted from inhibition of ChE and downregulation of muscarinic cholinergic receptors, rats were dosed with chlorpyrifos (CPF), an OP pesticide which inhibits blood and brain ChE of rats for weeks after a single injection. Long-Evans rats were trained to perform an appetitive test of memory and motor function and were then injected s.c. with 0, 60, 125 or 250 mg/kg of CPF in peanut oil and tested 5 days/week for 7 weeks. Unconditioned behavior was also rated for signs of cholinergic toxicity. CPF inhibited ChE activity in whole blood in a dose-related manner for more than 53 days. The degree and time course of ChE inhibition in blood and brain and the downregulation of muscarinic receptors in brain after 125 mg/kg of CPF closely paralleled the previously reported effects of 25 daily injections of 0.2 mg/kg of DFP. In addition, CPF-treated rats were subsensitive to oxotremorine-induced hypothermia for at least 32 days after CPF. However, functional deficits (in working memory and motor function) appeared within 2 days after injection of CPF and recovered within 3 weeks, long before ChE activity and receptor density returned to control levels. Thus, the effects of CPF were neither progressive nor as persistent as those seen during daily DFP injections. This difference suggests that the DFP-induced behavioral changes observed previously cannot be attributed entirely to its effects on ChE activity and changes in [3H]quinuclidinyl benzilate binding.
...
PMID:Behavioral and neurochemical effects of acute chlorpyrifos in rats: tolerance to prolonged inhibition of cholinesterase. 768 99

Intraspecies variation has been found to affect the physiological, behavioral, and biochemical responses to a variety of neurotoxicants, including the organophosphate diisopropyl fluorophosphate (DFP). However, there is little information on long-term physiological responses to neurotoxicant exposure using strain as a dependent variable. In the present study, radiotelemetry methodology was used to continuously monitor core temperature, heart rate, and motor activity for 4 d following administration of 1.5 mg/kg DFP (sc) in four common strains of rat: Sprague-Dawley (SD), Long-Evans (LE), Fischer 344 (F344), and Wistar (WST). The F344 rat was least susceptible to DFP in terms of both a minimal hypothermic response and recovery of the day-night difference in core temperature. The SD strain was unusual in that its heart rate was elevated relative to the other strains after DFP, in spite of a marked decrease in core temperature and motor activity. The LE strain exhibited the largest reduction in core temperature and heart rate following DFP. Serum and brain cholinesterase activity (ChE) measured 3 h after administration of 1.0 mg/kg DFP also indicated strain effects. The F344 showed less inhibition in these variables compared to the other strains, a response that may explain its attenuated thermoregulatory response to DFP. Overall, the inbred F344 rat demonstrated better resistance to DFP compared to the outbred strains. Therefore, the impact of genetic differences on sensitivity to neurotoxicants such as DFP could be an important tool in understanding the mechanism of action of these agents.
...
PMID:Strain differences in the laboratory rat: impact on the autonomic, behavioral, and biochemical response to cholinesterase inhibition. 775 89

Long-Evans female rats sustained electrolytic lesions of the fimbria and the dorsal fornix and, two weeks later, received intrahippocampal suspension grafts of fetal tissue. The grafts were prepared from regions including either the medial septum and the diagonal band of Broca (septal grafts), or the mesencephalic raphe (raphe grafts), or from both these regions together (co-grafts). All rats were submitted to a series of behavioural tests (home cage and open-field locomotion, spontaneous alternation, radial-arm maze and Morris water maze performance) run over two periods after grafting (one to nine weeks and 20-35 weeks). Two weeks after completion of behavioural testing, histological (acetylcholinesterase and Cresyl Violet staining) and/or neurochemical (choline acetyltransferase activity, high-affinity synaptosomal uptake of choline and serotonin, noradrenaline, serotonin and 5-hydroxyindolacetic acid concentrations) verifications were performed on the hippocampus. Compared to sham-operated rats, lesion-only rats exhibited hyperactivity which was transient in a familiar environment (home cage) and lasting in an unfamiliar one (open field), decreased rates of spontaneous T-maze alternation, and impaired memory performance in both the radial-arm maze and the Morris water maze. These rats also showed decreased cholinergic and serotonergic markers with a maximal depletion in the septal two-thirds of the hippocampus. Noradrenaline concentration tended to be increased in the dorsal third of the hippocampus, but was not modified in the other two-thirds. While septal grafts specifically increased the cholinergic markers and raphe grafts the serotonergic ones, neither of these grafts produced a lasting effect on any behavioural variable. Conversely, the co-grafts, which increased both the cholinergic and serotonergic markers in the septal two-thirds of the hippocampus, completely normalized the Morris water maze probe trial performance, but failed to affect any of the other behavioural variables. Our present results confirm that grafts of fetal neurons injected into the denervated hippocampus may induce a neurochemical recovery that depends on the anatomical origin of the grafted cells, and that co-grafting two fetal brain regions allows the combination of their individual neurochemical properties. Furthermore, our results show that these neurochemical effects of the co-grafts may be involved in the recovery of behavioural function observed in the water maze. However, somewhat paradoxically, those effects appear inefficient for inducing any recovery in other behavioural tasks, even in the radial-arm maze; which is assumed to measure similar spatial functions.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:The effects of intrahippocampal raphe and/or septal grafts in rats with fimbria-fornix lesions depend on the origin of the grafted tissue and the behavioural task used. 789 48

Male Long-Evans rats received micro-injections of either N-methyl-D-aspartate (NMDA) in the medial septum/vertical diagonal band (MS/DB), 5,7-dihyroxytryptamine (5,7-DHT) in the fimbria/fornix and cingulate bundle or combined NMDA/5,7-DHT micro-injections. NMDA administration caused considerable damage to the MS and enlarged the lateral ventricles. It reduced the activity of choline acetyltransferase as well as the intensity of acetylcholinesterase staining in the hippocampus. 5,7-DHT selectively reduced the concentration of hippocampal serotonin. The rats were assessed for spatial memory in the Morris water maze and the radial arm maze (reference and working memory version). The 5,7-DHT-induced lesion of hippocampal serotonin had no effect by itself on either task. However, it augmented the reference memory impairment caused by the NMDA-induced lesion and delayed the recovery from NMDA-induced impairment of working memory on the radial maze. Combined damage of hippocampal cholinergic and serotonergic afferents did not severely affect spatial memory.
...
PMID:Neurochemical, histopathological and mnemonic effects of combined lesions of the medial septal and serotonin afferents to the hippocampus. 792 64

Long-term behavioral and neurochemical effects of bilateral lesions to only the infracallosal component of the "so-called" septohippocampal pathways (cingular bundle, fimbria and fornix) have not been assessed. This experiment compared the behavioral, histochemical and neurochemical effects of supracallosal (SUPRA; cingular bundle) and infracallosal (INFRA; fimbria-fornix) hippocampal denervations in Long-Evans female rats. The rats were tested, over two periods (8-52 and 92-170 days postlesion), for open field locomotion, spontaneous alternation and radial-maze performance. Subsequently, histochemical or neurochemical determinations of cholinergic, serotonergic and noradrenergic hippocampal innervations were performed using acetylcholinesterase-staining, determination of high-affinity synaptosomal uptake of choline and serotonin, and measurement of hippocampal serotonin and noradrenaline concentrations by HPLC methods. Whatever behavioral test was considered, no significant effect was found in rats with SUPRA lesions, whereas rats with INFRA lesions were permanently impaired in all tests. Histochemical and neurochemical analyses showed hippocampal cholinergic as well as serotonergic markers to be substantially decreased in INFRA rats as compared to SHAM and SUPRA rats. The SUPRA rats exhibited a weak but significant reduction of both serotonergic and noradrenergic markers compared to SHAM and INFRA rats. These results suggest that lesions limited to the infracallosal pathway induce a hippocampal denervation sufficient to account for most of the behavioral, histochemical and neurochemical deficits classically reported following extensive lesions of the anterior hippocampal connections. Since the behavioral and neurochemical deficits were found to be lasting, it is suggested that bilateral infracallosal damage to the septohippocampal pathways might constitute an interesting paradigm of partial hippocampal deafferentation to investigate the effects of neural grafts or other treatments in an animal model of Alzheimer's disease.
...
PMID:Lesions of supracallosal or infracallosal hippocampal pathways in the rat: behavioral, neurochemical, and histochemical effects. 799 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---