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)

Diffuse plaques are the earliest Alzheimer-type lesions in Down's syndrome and are a putative marker for the preclinical stage of Alzheimer's disease (AD). As a cerebral cortical cholinergic deficit is one of the characteristics which defines AD, we examined the brains of individuals who had died without a history of neurological disease to determine whether this deficit is present in association with diffuse plaques. Of the 24 cases collected, 14 were older than 60 years of age (mean 69.2 years) and 10 were younger (mean 29.6 years). Of the 14 older cases, 9 had diffuse plaques in the entorhinal cortex (ECx) and/or inferior temporal gyrus (ITG). The older cases were divided into two groups (plaque-positive or plaque-negative cases). These groups did not differ significantly with respect to age, post-mortem delay, synaptophysin immunoreactivity or neurofibrillary tangle density. Cholinergic fibre densities were estimated in sections stained using acetylcholinesterase (AChE) enzyme histochemistry. Mean AChE fibre density was decreased in both the ITG and ECx (approximately 30% and 50% depletion, respectively) in the plaque-positive group compared to the plaque-negative group and in both areas the mean fibre density of the plaque-positive group was about 50% of that in the younger group. These results suggest that diffuse plaques in the non-demented elderly are associated with an accelerated age-related cortical cholinergic deficit and, therefore represent the preclinical stage of AD.
...
PMID:Cholinergic fibre loss associated with diffuse plaques in the non-demented elderly: the preclinical stage of Alzheimer's disease? 903 61

The initial stage of Alzheimer's disease is characterized by a neuropathological change in the entorhinal cortex. In a previous study it was shown that rats with excitotoxic lesion of entorhinal cortex showed an impaired acquisition of passive and active avoidance responses. In this study a rat with excitotoxic lesion of the entorhinal cortex was tested for 'more operant' behavioral learning (i.e., positive reinforcement operant learning). The hippocampus was also examined histologically as acetylcholinesterase-stained sections, and as synaptophysin immunostained sections and examined biochemically by liquid chromatography. Eight weeks after operation, the bilateral entorhinal cortex lesioned rats showed an impaired acquisition of positive reinforcement operant learning. The lesioned side of unilateral entorhinal cortex lesioned rats showed a decrease of acetylcholinesterase-positive fibers in the CA3, the dentate gyrus, and of synaptophysin-positive substances in the CA3. Biochemical study showed a decreased level of acetylcholine in the CA3, and in the dentate gyrus. The histological and biochemical findings are interpreted as indicating that the entorhinal cortex of the rat provides the major extrinsic synaptic input to the hippocampal formation via the circuit which serves as a relay passage through the dentate gyrus and via direct projections into the hippocampus. Behavioral findings confirmed the importance of the entorhinal cortex in memory acquisition and indicated that rats with a partial neuronal loss in the entorhinal cortex may be a useful model for the memory disturbance of Alzheimer's disease.
...
PMID:Effects of entorhinal cortex lesion on learning behavior and on hippocampus in the rat. 920 80

The presence of nerve fibers and terminals among Deiters' and Hensen's cells of the organ of Corti of the adult guinea pig is demonstrated using immunostaining for synaptophysin and neurofilaments, acetylcholinesterase histochemistry, and transmission electron microscopy. These nerve terminals appeared to form chemical synapses with Deiters' and Hensen's cells. Nerve fibers and synapses were more common in the apical as compared to the basal cochlea. The terminals were often present on basal appendages of Hensen's cells, which were rich in mitochondria and often contained a Golgi apparatus and dense core vesicles. Electron microscopy and immunostaining for neurofilaments showed that most Hensen's cells in the apical cochlea received innervation. Few of the nerve fibers and terminals were positive for acetylcholinesterase, which suggests that they were not collaterals of cholinergic olivocochlear fibers. The density of these fibers, as shown by immunohistochemistry for neurofilaments, was far greater than previous reports of GABA-ergic fibers, which suggests that they were not GABA-ergic olivocochlear fibers. The role of such fibers and synapses with supporting cells of the outer hair cell area is unknown. Determination of the origins and functions of these fibers will provide new insights into cochlear structure and function.
...
PMID:Morphologic evidence for innervation of Deiters' and Hensen's cells in the guinea pig. 921 24

In Hirschsprung's disease (HD), certain intestinal nervous plexuses are absent. Sprouting nerve endings contain different amounts of synaptophysin (SY), a protein and main constituent of acetylcholinesterase (AChE) storage compartments. Due to the lack of specific markers for synapses, a qualitative analysis of nerve endings of intestinal segments affected by HD has not yet been undertaken. For this study, resected colorectal specimens from patients with HD (n = 8, mean age 2.1 years) were investigated in parallel for AChE, SY, and content of small synaptic vesicles by biochemical, immunohistochemical, and electronmicroscopic means. In the microdissected muscular layer, reduced SY (1.4 microgram/mg total protein, normal 24 +/- 0.3) was observed. Immunohistochemistry showed in affected tissues reduced numbers of SY-positive nerve fibers and nerve endings, which in turn were thickened and distorted, in both the muscle proper and the muscularis mucosae. Combining both morphologic and biochemical findings, in HD the number of cholinergic vesicles in the remaining nerve endings seems to be increased as measured by SY, a marker molecule specific for synaptic vesicles. Our data also suggest that nerve endings in HD may contain high concentrations of cholinergic vesicles, paralleling the known high amounts of acetylcholine and AChE found in intestinal segments of patients with HD.
...
PMID:Qualitative and quantitative analysis of synapses in Hirschsprung's disease. 971 72

The adrenal medulla receives its major presynaptic input from sympathetic preganglionic neurons that are located in the intermediolateral (IML) column of the thoracic spinal cord. The neurotrophic factor concept would predict that these IML neurons receive trophic support from chromaffin cells in the adrenal medulla. We show here that adrenal chromaffin cells in the adult rat store neurotrophin (NT)-4, but do not synthesize or store detectable levels of BDNF or NT-3, respectively. Preganglionic neurons to the adrenal medulla identified by retrograde tracing with fast blue or Fluoro-Gold (FG) express TrkB mRNA. After unilateral destruction of the adrenal medulla, 24% of IML neurons, i.e., all neurons that are preganglionic to the adrenal medulla in spinal cord segments T7-T10, disappear. Administration of NT-4 in gelfoams (6 microgram) implanted into the medullectomized adrenal gland rescued all preganglionic neurons as evidenced by their presence after 4 weeks. NT-3 and cytochrome C were not effective. The action of NT-4 is accompanied by massive sprouting of axons in the vicinity of the NT-4 source as monitored by staining for acetylcholinesterase and synaptophysin immunoreactivity, suggesting that NT-4 may enlarge the terminal field of preganglionic nerves and enhance their access to trophic factors. Analysis of TrkB-deficient mice revealed degenerative changes in axon terminals on chromaffin cells. Furthermore, numbers of FG-labeled IML neurons in spinal cord segments T7-T10 of NT-4-deficient adult mice were significantly reduced. These data are consistent with the notion that NT-4 from chromaffin cells operates through TrkB receptors to regulate development and maintenance of the preganglionic innervation of the adrenal medulla.
...
PMID:TrkB and neurotrophin-4 are important for development and maintenance of sympathetic preganglionic neurons innervating the adrenal medulla. 973 48

When administered to rats, antibodies against acetylcholinesterase (AChE) selectively destroy presynaptic inputs to sympathetic ganglia. To investigate the mechanism of this immunolesion, we created an in vitro system in which relevant components could be manipulated. Freshly dissected rat superior cervical ganglia (SCG) were incubated 15-20 h at 37 degrees C in fresh human serum (a potent source of complement) with continuous oxygenation. More than 96% of neurons in six control ganglia retained synaptic inputs, as defined by action potentials or excitatory postsynaptic potentials (EPSP) upon stimulation of the preganglionic trunk. However, when anti-AChE antibodies were present (0.16 mg/ml), none of 61 neurons from six incubated ganglia showed synaptic responses although membrane potential and input resistance remained normal. Staining for AChE and synaptophysin (a synaptic vesicle marker) was also disrupted in ganglia exposed to AChE antibodies in complement-sufficient serum. When complement was eliminated by substituting serum that was heat-inactivated or deficient in C3, synaptic input was retained in 60-90% of neurons incubated with AChE antibodies. Choline acetyltransferase activity (ChAT), an enzymatic marker of cholinergic cytoplasm in sympathetic ganglia, was largely lost after incubation with AChE antibodies and serum. However, incubation with AChE antibodies in heat-inactivated serum, or serum that was deficient in C3 or C8, caused no measurable loss of ganglionic ChAT activity. These findings strongly implicate the complement cascade in the destruction of preganglionic sympathetic terminals that follows binding of AChE antibodies.
...
PMID:Complement-mediated lesion of sympathetic ganglia in vitro with acetylcholinesterase antibodies. 1040 83

Cholinesterase inhibitors (anti-ChEs) include a wide range of therapeutic, agricultural and warfare agents all aimed to inhibit the catalytic activity of the acetylcholine (ACh) hydrolysing enzyme acetylcholinesterase (AChE). In addition to promoting immediate excitation of cholinergic neurotransmission through transient elevation of synaptic ACh levels, anti-ChEs exposure is associated with long-term effects reminiscent of post-traumatic stress disorder. This suggested that exposure to anti-ChEs leads to persistent changes in brain proteins and called for exploring the mechanism(s) through which such changes could occur. For this purpose, we established an in vitro system of perfused, sagittal mouse brain slices which sustains authentic transcriptional responses for over 10 h and enables the study of gene regulation under controlled exposure to anti-ChEs. Slices were exposed to either organophosphate or cabamate anti-ChEs, both of which induced within 10 min excessive overexpression of the mRNA encoding the immediate early response transcription factor c-Fos. Twenty minutes later we noted 8-fold increases over control levels in AChE mRNA, accompanied by a 3-fold decrease in the mRNAs encoding for the ACh synthesizing enzyme choline acetyltransferase (ChAT) and the vesicular ACh transporter (VAChT). No changes were detected in synaptophysin mRNA levels. These modulations in gene expression paralleled those taking place under in vivo exposure. Of particular concern is the possibility that feedback processes leading to elevated levels of brain AChE may be similarly associated with low-level exposure to common organophosphorous anti-cholinesterases, and lead to long-term deleterious changes in cognitive functions.
...
PMID:Anticholinesterases induce multigenic transcriptional feedback response suppressing cholinergic neurotransmission. 1042 71

Human amyloid-beta1-42 has been suggested to be a pathogenetic factor in Alzheimer's disease. The precise mechanism by which this peptide causes the degeneration of neurons in the affected brain is not yet fully understood. By using immunohistochemistry we explored the inhibitory effects of human amyloid-beta1-42 applied in vivo on the fast axonal transport of acetylcholinesterase, the amyloid precursor protein, the vesicular acetylcholine transporter and synaptophysin in the sciatic nerve of rat. Our findings provide evidence for the in vivo neurotoxic effect of human amyloid-beta peptide.
...
PMID:Human amyloid-beta1-42 applied in vivo inhibits the fast axonal transport of proteins in the sciatic nerve of rat. 1064 15

The differentiated type of neuroblastomaxglioma hybrid cell line, NG108-15, has widely been used in in vitro studies instead of primary-cultured neurons. Here we examined whether NG108-15 cells can be used as a model for studying the neuronal differentiation process. We compared the expression of neuronal proteins (neurofilament 200 (NF200), phosphorylated-NF200 (p-NF200), microtubule associated protein 2, synaptophysin, syntaxin 1, choline acetyltransferase, and acetylcholinesterase (AChE)) and a glial protein (vimentin) between undifferentiated and differentiated NG108-15 cells by immunocytochemistry and immunoblot analysis. The expression of all neuronal proteins, with the exception of NF200 and p-NF200, was positive in differentiated cells, but almost negative in undifferentiated cells. On the other hand, cytoskeletal intermediate filaments (NF200 and p-NF200) for neurons and that (vimentin) for glia were present in both undifferentiated and differentiated cells. Furthermore, a high expression of AChE mRNA was confirmed in differentiated cells by reverse transcription-PCR analysis. Our results showed that even though the expression of cytoskeletal filaments does not change during differentiation of NG108-15 cells, these cells during differentiation can serve as an appropriate tool for investigating and understanding the mechanisms involved in neuronal development and differentiation.
...
PMID:Acquisition of neuronal proteins during differentiation of NG108-15 cells. 1086 77

Basic fibroblast growth factor-responsive neural stem cells (NSCs) derived from adult rat hippocampus were earlier demonstrated to generate neurons and glia. These stem-cell-derived neurons express GABA, acetylcholinesterase, tyrosine hydroxylase, or calbindin. It has not been clear, however, whether or not these stem-cell-derived neurons are able to form functional synapses. In the present study, we investigated the development of synapse formation by adult hippocampus-derived neural stem cells. NSCs from adult rat hippocampi and primary embryonic rat hippocampal neurons were cocultured on a glial feeder layer. Immunofluorescence studies revealed that some of the NSCs became immunoreactive for microtubule-associated protein 2ab, neurofilament 200, synaptobrevin, or synaptophysin. These cells possessed properties of functional neurons such as action potentials and miniature postsynaptic currents (mPSCs). The elicited mPSCs with rapid kinetics were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX), but not by bicuculline (excitatory mPSCs). The remaining mPSCs had slower kinetics and were blocked by bicuculline, but not by DNQX (inhibitory mPSCs). We considered that the neurons derived from the adult NSCs expressed both non-NMDA glutamate receptors and the GABA(A) receptors and formed functional synapses. Our results demonstrate that adult NSCs can differentiate into neurons with functional glutamatergic and GABAergic synaptic transmission in vitro and support the concept that such neurons could integrate into the neuronal circuitry.
...
PMID:Neurons generated from adult rat hippocampal stem cells form functional glutamatergic and GABAergic synapses in vitro. 1096 86


<< Previous 1 2 3 4 5 6 Next >>

---