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)

We have used an antiserum raised against mouse 2.5S NGF to examine the involvement of endogenous neurotrophins in the collateral sprouting of septohippocampal fibers in the adult rat brain. The antiserum was administered intraventricularly. Immunocytochemical techniques indicated that the injected antibodies penetrated into brain tissue that included the basal forebrain, cortex, striatum, corpus callosum, and hippocampus. Unilateral lesioning of the entorhinal cortex was done to evoke the sprouting of the cholinergic septohippocampal fibers. At 8 days postlesion, the sprouting was much advanced, as evidenced by an increase in density of the acetylcholinesterase (AChE) staining in the outer molecular layer (OML) of the dentate gyrus and by the associated increase in the absolute number of AChE-positive fibers in the OML. As well, there was a widening of the inner molecular layer (IML), interpreted as being due to sprouting of noncholinergic axons in that region. In rats injected daily with anti-NGF or anti-NGF Fab fragments, no increase in AChE density, or in the population of AChE-positive fibers, was observed in the OML. In contrast, the widening of the IML seemed to be unaffected by the anti-NGF treatment. No changes were observed in the AChE related parameters in the dentate gyrus of nonlesioned animals treated similarly for 8 days with anti-NGF; there was, however, a decrease of choline acetyltransferase (ChAT) immunostaining in the ChAT-positive cells of the basal forebrain. Our findings and the confirmation that our polyclonal anti-NGF also recognizes other members of the NGF neurotrophin family, specifically brain-derived neurotrophic factor and neurotrophin-3, indicate that at least one of these neurotrophins plays a key role in the collateral sprouting of the cholinergic septohippocampal fibers (but not that presumed to occur within the IML) following an entorhinal cortex lesion.
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PMID:Antibody to NGF inhibits collateral sprouting of septohippocampal fibers following entorhinal cortex lesion in adult rats. 147 72

Neurotrophins and neural cytokines are two broad classes of neurotrophic factors. It has been reported that ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) prevent the degeneration of axotomized neonatal motor neurons. In addition, BDNF is transported retrogradely to alpha-motor neurons following injection into the muscle, and patterns of BDNF expressed in spinal cord and muscle suggest a physiological role for this factor in motor neurons. In the present study, we characterize the effects of BDNF on axotomized neonatal facial motor neurons and extend these observations to adult models of motor neuron injury (axotomy-induced phenotypic injury of lumbar motor neurons). BDNF reduces axotomy-induced degeneration of neonatal neurons by 55% as determined by Nissl staining (percentage of surviving neurons in vehicle-treated cases, 25%; in BDNF-treated cases, 80%). Rescued neurons have an intact organelle structure but appear smaller and slightly chromatolytic on electron microscopic analysis. As demonstrated by intense retrograde labeling with horseradish peroxidase (HRP) applied to the proximal stump of the facial nerve, neurons rescued by BDNF have intact mechanisms of fast axonal transport. CNTF did not appear to have significant effects on neonatal motor neurons, but the lack of efficacy of this factor may be caused by its rapid degradation at the application site. BDNF is not capable of reversing the axotomy-induced reduction in transmitter markers [i.e., the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT) or the degrading enzyme acetylcholinesterase (AChE) in neonatal or adult animals or the axotomy-induced up-regulation of the low-affinity neurotrophin receptor p75NGFR (nerve growth factor receptor) in adult motor neurons. However, BDNF appears to promote the expression of p75NGFR in injured neonatal motor neurons. In concert, the findings of the present study suggest that BDNF can significantly prevent cell death in injured motor neurons. However, this neurotrophin may not be a retrograde signal associated with the induction and/or maintenance of some mature features of motor neurons, particularly their transmitter phenotype.
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PMID:Further characterization of the effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on axotomized neonatal and adult mammalian motor neurons. 751 7

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

Recent studies with nerve growth factor (NGF) have identified the pharmacological actions of this neurotrophin in a variety of animal models that mimic some of the neurotransmitter deficits that occur in Alzheimer's disease (AD, for reviews see Refs 7, 15, 17, 19). Based upon extensive pharmacological studies, NGF has been characterized as a crucial maintenance factor for adult cholinergic neurons of the septo-hippocampal and basalo-cortical pathways. Among the reported actions of NGF is an attenuation of lesion-induced decrements in presynaptic and postsynaptic cholinergic markers and functions in the hippocampal formation. Thus, in studies that used partial fimbriectomies to parallel the cholinergic neurodegeneration that occurs in AD, intraventricularly administered nerve growth factor prevented the loss of choline acetyltransferase (ChAT) and acetylcholinesterase immunoreactivity in the septum and increased a variety of presynaptic cholinergic markers involved in the synthesis, storage and release of the neurotransmitter acetylcholine (for reviews see Refs 7, 17, 19). More specifically, chronic NGF treatment attenuates lesion-induced reductions in hippocampal ChAT activity and high-affinity choline uptake, the end-result of which is an enhanced capacity to synthesize acetylcholine. This increased acetylcholine synthesis, in turn, appears to translate directly into augmented vesicular storage and release of the neurotransmitter. For instance, not only does NGF treatment reverse lesion-induced reductions in maximal binding densities of the acetylcholine vesicular transport marker [3H]vesamicol, but it also enhances acetylcholine release and turnover rate. NGF treatment also appears to restore the sensitivity of postsynaptic muscarinic receptors to agonist-induced stimulation following partial fimbriectomies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of chronic nerve growth factor treatment on hippocampal [3H]cytisine/nicotinic binding sites and presynaptic nicotinic receptor function following fimbrial transections. 807 84

Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-beta superfamily of growth factors with marked neurotrophic activity on midbrain dopaminergic neurons. To investigate whether this trophic activity is shared by central cholinergic neurons, we investigated the effects of GDNF treatment during development of the medial septal area in rats. Adult Fischer 344 rats received intraocular transplants of fetal septal forebrain tissue (embryonic Day 17) which was preincubated for 20 min with either GDNF or vehicle. The two treatment groups subsequently received weekly intraocular injections of either GDNF (0.5 microgram in 5 microliters/injection) or vehicle for 6 weeks following transplantation. Transplants treated with GDNF grew twice as large as control grafts treated with vehicle. Immunohistochemical evaluations of the transplants revealed that there was no difference between the two groups in terms of acetylcholinesterase or low affinity neurotrophin receptor (p75) staining. In contrast, a significant increment in the number of GABA-ergic neurons was observed in transplants that received GDNF, as compared to vehicle-treated grafts. The overall number of neurons within the transplanted tissue was also elevated in the experimental group. There was no difference between the two groups in the distribution or density of astrocytes in the grafted tissue, as evidenced by immunohistochemistry with antibodies directed against glial fibrillary acidic protein. These results indicate that basal forebrain GABA-ergic neurons may be dependent on GDNF for their survival and/or for GABA synthesis, but that the cholinergic neurons in this area appear to be unaffected by GDNF administration during development.
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PMID:Effects of GDNF on fetal septal forebrain transplants in oculo. 881 51

These studies tested the hypothesis that survival-promoting effects of neurotrophins on basal forebrain cholinergic neurons are enhanced under stress. Septal neurons from embryonic day 14-15 rats exposed for 10-14 d to neurotrophin [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4 (NT-4), each at 100 ng/ml] showed a two- to threefold increase in choline acetyltransferase (ChAT) activity, with little evidence of synergistic interactions. Neurotrophins produced no significant increase in the survival of total or acetylcholinesterase (AChE)-positive neurons at moderate plating density (1200-1600 cells/mm2). However, with very low plating densities (2-28 cells/mm2) BDNF, NT-3, and NT-4 (but not NGF) increased total neuronal survival, and BDNF increased survival of AChE-positive neurons. NGF and BDNF enhanced ChAT activity and survival of cholinergic neurons after a 24 hr hypoglycemic stress, even when added 1 hr after stress onset. All four tested neurotrophins increased total neuronal survival after hypoglycemic stress. These results suggest that neurotrophins are important for preservation of central cholinergic function under stress conditions, with different neurotrophins protecting against different stresses. The stress-associated survival-promoting effects of neurotrophins were not limited to the cholinergic subpopulation.
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PMID:Neurotrophin effects on survival and expression of cholinergic properties in cultured rat septal neurons under normal and stress conditions. 882 7

The postnatal development of intraadrenal ganglion neurons was studied in rat by using indirect immunohistochemistry and in situ hybridization. The large neuropeptide tyrosine (NPY)-expressing ganglion neurons (type I ganglion neurons) matured postnatally, with marked increases in acetylcholinesterase (AChE)-, neurofilament 10 (NF10)-, and tyrosine hydroxylase (TH)-like immunoreactivities (LIs) paralleled by increasing levels of mRNAs encoding NPY, low-affinity neurotrophin receptor (LANR), and tropomyosin kinase receptor (trk). The smaller vasoactive intestinal polypeptide (VIP)-immunoreactive (IR) ganglion neurons (type II ganglion neurons) expressed increasing levels of VIP mRNA postnatally and also contained immunoreactive nitric oxide synthase (NOS) and its mRNA. These type II ganglion neurons appeared to be relatively mature already at postnatal day (P2) and did not express detectable levels of LANR or trk mRNAs. The cell size of both the type I and type II ganglion neurons increased about 2.5-fold postnatally. The type I ganglion neurons formed more densely packed clusters with increasing age, whereas the type II ganglion neurons were spread out in small groups or individually, mainly in the peripheral parts of the medulla, and appeared to fulfill their migration into the medulla and/or to the inner regions of the cortex early postnatally, possibly after establishing contact with their cortical targets. We suggest that the type I ganglion neurons represent sympathetic ganglion neurons of the same origin as the chromaffin cells and that they mature mainly postnatally. The development of the type II (VIP/NOS) ganglion neurons takes place earlier; however, their phenotype remains more uncertain.
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PMID:Phenotype of intraadrenal ganglion neurons during postnatal development in rat. 884 13

TrkA high-affinity receptors are essential for the normal development of sympathetic paravertebral neurons and subpopulations of sensory neurons. Paravertebral sympathetic neurons and chromaffin cells of the adrenal medulla share an ontogenetic origin, responsiveness to NGF, and expression of TrkA. Which aspects of development of the adrenal medulla might be regulated via TrkA are unknown. In the present study we demonstrate that mice deficient for TrkA, but not the neurotrophin receptor TrkB, show an early postnatal progressive reduction of acetylcholinesterase (AChE) enzymatic activity in the adrenal medulla and in preganglionic sympathetic neurons within the thoracic spinal cord, which are also significantly reduced in number. Quantitative determinations of specific AChE activity revealed a massive decrease (-62%) in the adrenal gland and a lesser, but still pronounced, reduction in the thoracic spinal cord (-40%). Other markers of the adrenal medulla and its innervation, including various neuropeptides, chromogranin B, secretogranin II, amine transporters, the catecholamine-synthesizing enzymes tyrosine hydroxylase and PNMT, synaptophysin, and L1, essentially were unchanged. Interestingly, AChE immunoreactivity appeared unaltered, too. Preganglionic sympathetic neurons, in contrast to adrenal medullary cells, do not express TrkA. They must, therefore, be affected indirectly by the TrkA knock-out, possibly via a retrograde signal from chromaffin cells. Our results suggest that signaling via TrkA, but not TrkB, may be involved in the postnatal regulation of AChE activity in the adrenal medulla and its preganglionic nerves.
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PMID:Reduced acetylcholinesterase (AChE) activity in adrenal medulla and loss of sympathetic preganglionic neurons in TrkA-deficient, but not TrkB-deficient, mice. 899 44

Neurotrophic effects of human brain-derived neurotrophic factor (hBDNF) on forebrain cholinergic neurons were addressed after ex vivo gene transfer to the intact adult rat brain, using a conditionally immortalized neural progenitor cell line (CINP) engineered to secrete the neurotrophin (2.8 ng/h/10(6) cells). This cell line was derived by repeated retroviral infection of the parental neural precursor line HiB5 followed by subcloning. The cells survived well in the host brain for long periods of time (up to 4 weeks), and induced a hypertrophic response of cholinergic neurons (positive for acetylcholinesterase, choline acetyltransferase or low-affinity nerve growth factor receptor) in the nucleus basalis magnocellularis and striatum. We conclude that these cholinergic cell groups are responsive to a low-level supply (nanograms per day) of BDNF in vivo when the neurotrophin is administered locally in the vicinity of the cell bodies.
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PMID:Ex vivo gene transfer of brain-derived neurotrophic factor to the intact rat forebrain: neurotrophic effects on cholinergic neurons. 908 24

After unilateral entorhinal cortex lesion cholinergic septohippocampal fibres sprout in the denervated fascia dentata. This process is dependent on neurotrophin changes following the lesion. Thus, there is an up-regulation of nerve growth factor and brain-derived neurotrophic factor messenger RNA expression in the denervated granule cells which is detectable 4 h postlesion and returns to control levels by 24 h. Here, using a competitive polymerase chain reaction and in situ hybridization, a transient neurotropin messenger RNA increase could be demonstrated bilaterally following unilateral electrolytic entorhinal cortex lesion. Treatment of the animals with the N-methyl-D-aspartate receptor antagonist dizocilpine maleate blocked this messenger RNA increase, suggesting an involvement of this receptor type in the neurotrophin changes. However, in spite of this blockade, the typical cholinergic sprouting response as visualized with acetylcholinesterase histochemistry was present in animals four weeks after entorhinal cortex lesion. These data suggest that brief initial changes in neurotrophin messenger RNA expression in dentate granule cells are not responsible for the induction of the cholinergic sprouting. Changes in neurotrophin messenger RNA expression occurring immediately postlesion may be linked to glutamate release from entorhinal terminals resulting from the electrolytic lesion of the projection cells in the entorhinal cortex. We hypothesize that later changes in neurotrophin expression, for example in glial cells, are more likely to be related to the cholinergic sprouting process.
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PMID:Cholinergic sprouting in the rat fascia dentata after entorhinal lesion is not linked to early changes in neurotrophin messenger RNA expression. 927 89


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