Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular layer of the dentate gyrus exhibits extensive circuit and receptor reorganization after entorhinal lesions and in Alzheimer's disease, including decreased adenosine (A1) receptor binding in the terminal zone of damaged perforant path fibers. We examined the adenosine-sensitivity of evoked synaptic activity recorded from the rat dentate gyrus molecular layer in hippocampal slices prepared after electrolytic lesions were placed in approximately the middle third of the entorhinal cortex. Extracellular field potentials (EFPs) recorded in slices prepared from animals two days post-lesion were small, upward-going, and exhibited paired-pulse potentiation, but by two weeks post-lesion EFPs had recovered to large, downward-going responses that exhibited paired-pulsed depression. EFPs recorded from two week post-lesion slices were about 2-fold more sensitive (P < or = 0.05) to exposure to adenosine when compared to EFPs recorded from slices from unlesioned animals. Adenosine-induced reduction of paired-pulse depression was similar between unlesioned and post-lesion slices. AChE histochemistry performed after recording revealed dense staining in the dentate gyrus molecular layer of post-lesion slices as compared to slices from unlesioned animals, confirming that sprouting of cholinergic fibers occurred as expected from previous entorhinal lesion studies. Autoradiography performed on adjacent slices showed a decrease in binding to A1-adenosine receptors in the dentate gyrus molecular layer in post-lesion slices as compared to slices from unlesioned animals, indicating that there was a loss of presynaptically located A1-adenosine receptors on damaged perforant pathway terminals. These results indicate that, in addition to the recovery of the major excitatory signal to the hippocampus after entorhinal cell loss, this signal is more sensitive to modulation by adenosine, suggesting an increase in A1-adenosine receptor efficacy in the reinnervated region.
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PMID:Increased sensitivity to adenosine in the rat dentate gyrus molecular layer two weeks after partial entorhinal lesions. 850 4

We examined the effects of p.o. administered 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8- yl)-1-propanone fumarate (TAK-147), a novel AChE inhibitor, on impaired learning and memory in animal models. At 1 to 3 mg/kg, TAK-147 ameliorated the passive avoidance deficit induced by diazepam. TAK-147 did not affect delayed-matching-to-position (DMTP) performance of normal rats at doses of 1 to 30 mg/kg assessed by using a three-lever operant chamber, but 9-amino-tetrahydroacridine disrupted the DMTP response at 5 to 20 mg/kg. Scopolamine (0.02-0.1 mg/kg s.c.) impaired DMTP performance, whereas methylscopolamine did not affect the DMTP task. TAK-147 ameliorated the impairment of DMTP performance induced by scopolamine without affecting the general behavior of the rats; however, 9-amino-tetrahydroacridine produced no significant amelioration of the impairment. The intraventricular injection of AF64A disrupted differential-reinforcement-of-low-rate 10-sec performance in rats, as demonstrated by marked decreases in reinforcement rate and response efficiency. TAK-147 slightly increased the reinforcement rate in AF64A-treated rats at a low dose of 1 mg/kg, but the effect was not significant statistically. TAK-147 had no significant effect on the duration of immobility in rats in a forced swimming test at doses of 2 to 10 mg/kg. 9-Amino-tetrahydroacridine prolonged the duration of immobility at 5 to 20 mg/kg. Furthermore, TAK-147 reversed reserpine-induced hypothermia and ptosis in mice at doses of 3 to 10 mg/kg, a result that implies an antidepressant-like action. These results indicate that TAK-147 ameliorates learning and memory impairment in animal models without affecting the general behavior or causing behavioral depression and suggest that TAK-147 may be useful for the treatment of Alzheimer's disease.
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PMID:Effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1 -H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, on impaired learning and memory in animal models. 866 90

Galanin (GAL)-immunoreactive axon terminals on motor endplates of the esophageal striated muscles were demonstrated in mice, guinea-pigs and rats. The GAL-terminals innervated 33% of AChE-reactive motor endplates in mice and 6% of those in guinea-pigs. Double immunostaining revealed that separate GAL- and CGRP-positive terminals were localized within the same motor endplates in mice and rats. The GAL and CGRP terminals had different morphologies. No CGRP-immunoreactivity was found on motor endplates of the guinea-pig esophagus. Double immunostaining in rats showed that 68% of motor endplates with CGRP-nerve terminals were also supplied by GAL-nerve terminals, suggesting that the majority of esophageal striated muscles receive a dual innervation of GAL-and CGRP/ACh-containing terminals. By immuno-electronmicroscopy in the rat esophagus. GAL-immunoreaction was found in a small type of nerve terminals that possessed many large cored vesicles (90-130 nm) with intense immunoreaction. Larger GAL-negative nerve terminals with a cluster of small clear vesicle (40-50 nm), which seemed to be ACh-containing nerve terminals, were adjacent to a depression or slight protrusion of the sarcolemma and well-developed folds in the muscle fibers. At the motor endplates, the GAL-positive terminals made a synaptic contact via basement membrane with the sarcolemma of the muscle fibers, which was characterized by post-synaptic intense electron density. In most of all situations, in which the GAL-positive terminals and GAL-negative or -positive terminals were adjacent to each other and were also apposed to the striated muscles, the terminals were separated by attenuated sheet- or tongue-like cytoplasmic processes that appeared to originate from Schwann cells. Thus, the GAL-nerve terminals seem to provide a direct innervation of the striated muscle fibers rather than innervating the ACh-containing motor nerve terminals adjacent to the GAL-terminals.
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PMID:Galanin-containing nerve terminals that are involved in a dual innervation of the striated muscles of the rat esophagus. 889 24

A clinical trial was designed to evaluate the effects of diminazene aceturate and its stabiliser antipyrine on serum pseudocholinesterase (PChE) and red blood cell acetylcholinesterase (RBC AChE) in dogs with babesiosis. The trial was conducted on naturally occurring, uncomplicated cases of babesiosis (n = 20) that were randomly allocated to groups receiving a standard therapeutic dose of diminazene aceturate with antipyrine stabiliser (n = 10) or antipyrine alone (n = 10). Blood was drawn immediately before and every 15 minutes for 1 hour after treatment. Plasma PChE showed a 4% decrease between 0 and 60 min within the treatment group (p < 0.05). No statistically significant differences were found between the treatment and control groups at any of the time intervals for PChE. There was an increase in RBC AChE activity at 15 min in the treatment group (p < 0.05). No significant differences were found between the treatment and control groups at any time interval for RBC AChE. In view of the difference in PChE, samples from additional, new cases (n = 10) of canine babesiosis were collected to identify the affect of the drug over 12 hours. No significant depression was identified over this time interval. The results suggests that the underlying mechanism in producing side-effects, when they do occur, is unlikely to be through cholinesterase depression.
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PMID:The effect of diminazene aceturate on cholinesterase activity in dogs with canine babesiosis. 956 93

The urinary excretion rates of dimethyl-phosphate, -phosphorothioate and -phosphorodithioate were studied in six persons of whom four had ingested a concentrated solution of malathion and two of thiometon. The concentration decrease of single and total dimethylphosphorus metabolites was biphased, with a fast initial rate and a slow later rate. The excretion rate of total metabolites in the faster phase depended on the initial concentration in urine. At concentrations higher than 100 nmol/mg creatinine, the excretion half-times ranged from 7.5 to 15.4 h and at concentrations between 52 and 95 nmol/mg creatinine from 34.7 to 55.4 h. Non-metabolized malathion was detected only in one urine sample collected from one person immediately after hospitalization. Two persons poisoned with malathion were taken blood serum samples for the analysis of the parent pesticide and its metabolites on a daily basis after hospitalization. The parent pesticide was detectable in the serum only one day after the poisoning. The concentration of total malathion dimethylphosphorus metabolites in serum decreased very quickly within 1.5 days after hospitalization. The total metabolite elimination half-times were 4.1 and 4.7 h in the initial phase, and 53.3 and 69.3 days in the later slower elimination phase. There was no correlation between maximum concentrations of total metabolites measured in serum and/or urine on the day of admission to hospital and the initial depression of serum cholinesterase (BChE, EC 3.1.1.8) and erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7).
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PMID:Dimethylphosphorus metabolites in serum and urine of persons poisoned by malathion or thiometon. 1042 86

We have exploited the complementary arrangement of afferents in a coronal slice (300-400 microm) of the rat olfactory tubercle (OT) maintained in vitro to investigate transmission in two separate synaptic pathways. We recorded extracellular responses within the OT dense cell layer in slices and stimulated either the outermost layer to activate primary olfactory fibres or deeper to activate secondary input. Superficial stimulation produced a synaptic potential with superimposed population spike. This interpretation was based on blockade by calcium removal from the bathing medium and the use of the glutamate antagonist DNQX (10 microM); the spike was found to be selectively suppressed by tetrodotoxin applied near the cells. The spike, but not the synaptic wave, was depressed by 12 mM Ca2+ and enhanced by 1 mM Ba2+ in the bathing medium. Deep stimulation to activate association and intrinsic fibres elicited a nerve volley followed by a later response, also blocked by Ca2+ removal or 10 microM DNQX. It was unaffected by high Ca2+ or Ba2+, hence resulting from synaptic and not action current flow. Removal of Mg2+ from the bathing medium revealed an NMDA component of synaptic transmission at both loci that was selectively blocked by D-AP-5. The deep synaptic response, only, was depressed by carbachol IC50 7 microM or muscarine IC50 13 microM. This depression was also induced by AChE inhibitors eserine or tacrine and was antagonized by 1 microM atropine or 5-10 microM clozapine. These results characterize transmission in the OT and demonstrate a role for muscarinic modulation of deeper synapses in the OT that is influenced by psychotherapeutic drugs.
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PMID:Electrophysiological characterization of laminar synaptic inputs to the olfactory tubercle of the rat studied in vitro: modulation of glutamatergic transmission by cholinergic agents is pathway-specific. 1135 28

Methyl parathion induced alterations in the level of monoamines, viz. norepinephrine, dopamine and serotonin were studied in discrete regions of developing central nervous system of rat pups. A significant decrease in the level of monoamines noticed in methyl parathion toxicosis may be related to the altered neuronal activity and inefficiency, leading to depression and impairment in various behavioural activities. In contrast to AChE inhibition, monoamine oxidase (MAO) activity showed an increasing trend and it could cause deamination of catecholamines and accumulation of its metabolites. This suggests that an increased AChE inhibition may indirectly stimulate MAO activity in developing rat pups exposed to methyl parathion.
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PMID:Methyl parathion induced alterations in monoaminergic system of developing rat pups. 1149 89

CHF2819 is a novel orally active acetylcholinesterase inhibitor (AChEI) developed for the treatment of Alzheimer's disease (AD). CHF2819 is a selective inhibitor of AChE, it is 115 times more potent against this enzyme than against butyrylcholinesterase (BuChE). Moreover, CHF2819 is more selective for inhibition of central (brain) AChE than peripheral (heart) AChE. In vivo CHF2819, 0.5, 1.5, and 4.5 mg/kg p.o., significantly and in dose-dependent manner increased acetylcholine (ACh) levels in hippocampus of young adult rats. Moreover, aging animals, with lower basal ACh levels than young adult rats, also exhibit a marked increase in hippocampal levels of this neurotransmitter after administration of CHF2819. At 1.5 mg/kg p.o. CHF2819 attenuated scopolamine-induced amnesia in a passive avoidance task. Furthermore, it decreased dopamine (DA) levels and increased extracellular levels of 5-hydroxytryptamine (5-HT) in the hippocampus, without modifying norepinephrine (NE) levels. By oral administration to young adult rats CHF2819 did not affect extracellular hippocampal levels of glutamate (Glu), aspartate (Asp), gamma-aminobutyric acid (GABA), taurine (Tau), arginine (Arg) or citrulline (Cit). Functional observational battery (FOB) screening demonstrated that CHF2819 (1.5 and 4.5 mg/kg p.o.) does not affect activity, excitability, autonomic, neuromuscular, and sensorimotor domains, as well as physiological endpoints (body weight and temperature). CHF2819 induced, however, involuntary motor movements (ranging from mild tremors to myoclonic jerks) in a dose-dependent manner. The neurochemical and behavioral profiles of CHF2819 suggest that this orally active novel AChEI could be of clinical interest for the treatment of Alzheimer-type dementia associated with multiple neurotransmitter abnormalities in the brain. In particular, CHF2819 might be a useful therapeutic drug for AD patients with cognitive impairment accompanied by depression.
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PMID:CHF2819: pharmacological profile of a novel acetylcholinesterase inhibitor. 1207 May 26

Multiple behavioural and psychological symptoms of dementia (BPSD) are commonly associated with all dementia subtypes, and worsen during disease progression. BPSD arise due to impairment of cholinergic function in the cortex, hippocampus and related limbic systems. Recent studies have investigated the effect of cholinesterase inhibitors on BPSD. The dual acetylcholinesterase/butyrylcholinesterase (AChE/BuChE) inhibitor rivastigmine was shown to have several potential advantages over the AChE-selective inhibitors donepezil and galantamine for the treatment of BPSD. Rivastigmine appears to be effective across the range of dementia severity from mild to severe, and across the spectrum of dementia (Alzheimer's disease [AD], the AD variant with Lewy bodies, Parkinson's disease dementia and vascular dementia subtypes). It also appears to have a disease-modifying potential. Rivastigmine improved a wider range of behavioural symptoms (apathy, anxiety/depression, hallucinations and delusions) than donepezil and galantamine (which improved apathy and depression/anxiety only). Unlike donepezil, rivastigmine reduced the need for psychotropic medications to treat BPSD. Dual inhibition of AChE and BuChE and brain-region selectivity through preferential inhibition of the G1 isoform of AChE may provide the underlying reasons for the apparently greater and broader efficacy of rivastigmine over AChE-selective inhibitors for the treatment of BPSD. However, randomised, controlled trials are required to compare dual inhibitors, such as rivastigmine, and AChE-selective agents, to confirm and quantify any differences in their effects on BPSD.
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PMID:The efficacy of cholinesterase inhibitors in treating the behavioural symptoms of dementia. 1213 65

The blood of 76 cacao farmers from Southwestern Nigeria was monitored for erythrocyte cholinesterase enzyme activity (AChE) and hemoglobin values before and after insecticide application. Eight farmers had 30% to 50% baseline AChE activity, which suggests chronic organophosphate insecticide poisoning. AChE activity inhibition suggestive of occupational exposure (20% to 30%) was manifested by 28% of the farmers, whereas 30% to 50% inhibition suggestive of hazard was manifested by 11%. Significantly depressed post-insecticide application hemoglobin values were similarly recorded among the farmers. AChE activity inhibition, depression in hemoglobin values, and the years of involvement of the farmers in insecticide application on cacao, were positively correlated. Occupational exposure hazard due to organophosphate insecticides is therefore real among cacao farmers in Southwestern Nigeria. Regular biomonitoring of their blood for AChE activity and hemoglobin level is necessary.
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PMID:Erythrocyte cholinesterase enzyme activity and hemoglobin values in cacao farmers of southwestern Nigeria as related to insecticide exposure. 2014


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