Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basal forebrain cholinergic neurons respond in vitro and in vivo to nerve growth factor (NGF) and to brain-derived neurotrophic factor (BDNF). It is not clear to what extent the neurons that respond to these two factors, or to neurotrophin-3 or -4/5 (NT-3; NT-4/5) are identical or only partially overlapping populations. We have addressed this issue in cultures of basal forebrain neurons derived from 2-week-old postnatal rats, using choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) as cholinergic markers. Cholinergic neuron survival was enhanced in the presence of NGF, BDNF and NT-4/5. NT-4/5 was as effective as BDNF. NT-3 was without effect at this age, although in cultures derived from embryonic forebrain, cholinergic differentiation was induced by NT-3. Cotreatment with NGF and BDNF resulted in small, but consistent increases in the number of ChAT-positive neurons, compared with either factor alone. NT-4/5 was also found to be additive with NGF, whereas cotreatment with BDNF and NT-4/5 showed no additivity. NT-3 had no additive effects with any other neurotrophin on any cholinergic parameters in postnatal cultures. Taken together, the results indicate the existence in postnatal rat brain of a large overlapping population of cholinergic neurons that are responsive to ligands for the neurotrophin receptors TrkA (NGF) and TrkB (BDNF and NT-4/5), but not TrkC (NT-3), and small distinct populations that show specificity for NGF or BDNF but not both. We hypothesize that cholinergic neurons projecting into different regions of the hippocampus may derive trophic support from distinct neurotrophins.
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PMID:Cultured basal forebrain cholinergic neurons from postnatal rats show both overlapping and non-overlapping responses to the neurotrophins. 755 37

Prior studies examining the dependence of basal forebrain cholinergic neurons (BFCNs) on nerve growth factor (NGF) for survival have reached differing conclusions depending on the experimental paradigm employed, suggesting the importance of environmental and developmental variables. The present study examined the NGF dependence of BFCNs and modulatory effects of target (cortical) neurons under the controlled conditions of dissociated cell cultures. Initial experiments found BFCNs (identified by using choline acetyltransferase immunocytochemistry) in pure basal forebrain (BF) cultures to be dependent on NGF between the 2nd and 4th week in vitro. During that developmental period, NGF deprivation for 3 days, induced by application of anti-NGF antibody, resulted in degeneration of over 80% of BFCNs, whereas at earlier or later times, BFCNs were largely resistant to NGF deprivation. When BF neurons were plated together with cortical neurons (as dissociated co-cultures), the BFCNs grew neuritic processes (labeled with acetylcholinesterase histochemistry) that appeared to specifically target cortical neurons; electron microscopy revealed that synapses formed between these cells. BFCNs in co-cultures were more resistant to NGF deprivation, were larger, and had much more extensive neuritic growth than BFCNs in pure BF cultures. The resistance of BFCNs to NGF deprivation provided by cortical neurons could be largely reproduced by addition of other trophic factors (brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT3; neurotrophin 4/5, NT4/5; or glial-derived neurotrophic factor, GDNF) during NGF deprivation in pure BF cultures. These results suggest that developing BFCNs undergo a critical period requiring trophic influences that may be provided by NGF or other trophic factors, as well as unknown factors derived from cortical neurons.
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PMID:Cultured basal forebrain cholinergic neurons in contact with cortical cells display synapses, enhanced morphological features, and decreased dependence on nerve growth factor. 888 38

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.
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PMID:TrkB and neurotrophin-4 are important for development and maintenance of sympathetic preganglionic neurons innervating the adrenal medulla. 973 48

We examined the potential influences of muscle-derived neurotrophins on the acetylcholinesterase (AChE) gene expression of adult rat motoneurons. Seven days after facial nerve transection, both AChE mRNA and enzyme activity levels were markedly reduced in untreated and vehicle-treated facial motoneurons, suggesting positive regulation of motoneuron AChE expression by muscle-derived factors. Because skeletal muscle is a source of neurotrophin-3 (NT-3), NT-4/5, and BDNF, these neurotrophins were individually infused onto the proximal nerve stump for 7 d, beginning at the time of axotomy. The trkB ligands NT-4/5 and BDNF prevented the downregulation of AChE mRNA and enzymatic activity, as determined by in situ hybridization, biochemical assay, and histochemical visualization of enzyme activity. In contrast, NT-3 had limited effects, and NGF was without effect. Because motoneurons normally express both trkB and trkC receptors and the trkC ligand NT-3 is the most abundant muscle-derived neurotrophin, we investigated possible reasons for the limited effects of NT-3. In situ hybridization and reverse transcription-PCR both revealed a downregulation of trkC mRNA in axotomized motoneurons, which contrasted the upregulation of trkB expression. Furthermore, isoforms of trkC were detected carrying insertions within their kinase domains, known to limit certain trkC-mediated signal transduction pathways. Because the changes in trkB and trkC mRNA levels were not significantly altered by neurotrophin infusions, it is unlikely they were induced by loss of muscle-derived neurotrophins. These results demonstrate that NT-4/5 and BDNF stimulate AChE gene expression in motoneurons and support the concept that muscle-derived trkB ligands modulate the cholinergic phenotype of their innervating motoneurons.
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PMID:Acetylcholinesterase gene expression in axotomized rat facial motoneurons is differentially regulated by neurotrophins: correlation with trkB and trkC mRNA levels and isoforms. 982 49