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

We have established a primary culture technique for neuronal cells from rat basal forebrain from postnatal day 58 (P58) to study the effects of neurotrophic factors on the neurons. The survival of acetylcholinesterase (AChE)-positive neurons of 2-week-old rat septum has already been reported to be strongly supported by nerve growth factor (NGF) in culture. In this culture study of neurons from adult rat brains, the survival of AChE-positive neurons from P58 rat septum was slightly improved by NGF, although low affinity NGF receptor expression was also observed on cultured P58 rat septum neurons as well as on those from 2-week-old rats. The addition of basic fibroblast growth factor (bFGF) improved the survival of AChE-positive neurons cultured from P58 rat septum, but did not promote the survival of neurons from P12 rat septum. These results suggest that NGF changes to a maintenance factor in adult rat brain from a survival factor in postnatal 2-week-old rats. The survival of cholinergic neurons in culture of adult rat septum might be supported by factor(s) other than NGF, such as bFGF.
 ...
PMID:Effects of nerve growth factor and basic fibroblast growth factor on survival of cultured septal cholinergic neurons from adult rats. 148 88

Ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor (bFGF) were tested for effects on sprouting by motor neurons innervating the adult mouse gluteus muscle. Factors were delivered by subcutaneous injection directly over the surface of the superior gluteus muscle once daily for 7 d and then end plates and axons were visualized by combined silver and cholinesterase staining. CNTF (500 ng daily) induced sprouting both from end plates and from the subset of nodes of Ranvier that are closest to the end plate. The effect of CNTF was potentiated twofold by coadministration of bFGF at doses of 2-20 ng daily, whereas treatment with bFGF alone failed to induce sprouting from either end plates or nodes of Ranvier. The sprouting stimulus delivered by the factors showed limited penetrance into the muscle and restricted lateral spread from the injection site.
 ...
PMID:Induction of motor neuron sprouting in vivo by ciliary neurotrophic factor and basic fibroblast growth factor. 149 54

Nerve growth factor (NGF), a well-characterized target-derived growth factor, has been postulated to promote neuronal differentiation and survival of the basal forebrain cholinergic neurons. In the present paper, we demonstrate that a developmental change in NGF action occurs in postnatal rat basal forebrain cholinergic neurons in culture. Firstly, NGF acts as maturation factor by increasing choline acetyltransferase (ChAT) activity and acts later as a survival factor. In dissociated cell cultures of septal neurons from early postnatal (P1-4) rats, ChAT activities were increased by the addition of NGF. That is, ChAT activities in P1 septal cells cultured for 7 days was increased 4-fold in the presence of NGF at a concentration of 100 ng/ml. However, the number of the acetylcholinesterase (AChE)-positive neurons was not significantly different between these groups. In contrast, septal neurons from P8 to P14 rats showed different responses to NGF. Although the P14 septal neurons in culture for 7 days without NGF lost about half of the ChAT activity during a 7-day cultivation, cells cultured with NGF retained the activity at the initial level. The number of AChE-positive neurons counted in cultures with NGF was much greater than the number without NGF. These results suggest that, during the early postnatal days, the action of NGF on the septal cholinergic neurons in culture changes from induction of ChAT activity to the promotion of cholinergic neuronal cell survival. During this developmental period in vivo, septal neurons are terminating their projections to the hippocampal formation. Similar NGF-regulated changes in cholinergic neurons were observed in cultured postnatal neurons from vertical limb of diagonal band. An analogy has been pointed out between the neuronal death of the basal forebrain cholinergic neurons and a similar neuronal death in senile dementia, especially Alzheimer's type. The work reported here might present a possibility that NGF could play a role in preventing the loss of the basal forebrain cholinergic neurons in this disease.
 ...
PMID:Developmental change in the nerve growth factor action from induction of choline acetyltransferase to promotion of cell survival in cultured basal forebrain cholinergic neurons from postnatal rats. 335 32

Ciliary neurotrophic factor is known to exert both survival and differentiative actions on a number of neuronal populations of the peripheral and central nervous systems. In this study we have compared the trophic effects of ciliary neurotrophic factor and nerve growth factor on developing septal neurons of the rat in vitro. Fetal septal neurons were grown in vitro under glass coverslips in sandwich culture. Septal cultures grown for 14 days in the continual presence of nerve growth factor contain a population of cholinergic neurons that stain intensely for the low-affinity nerve growth factor receptor (p75NGFR), choline acetyltransferase and acetylcholinesterase. Without added nerve growth factor, few neurons stain for these markers. Ciliary neurotrophic factor addition for 14 days from plating in the absence of exogenous nerve growth factor results in the appearance of a population of neurons that stains for p75NGFR. This population is similar in number to that seen in nerve growth factor-treated cultures but is not immunoreactive for choline acetyltransferase and is significantly smaller in mean cross-sectional area. Delayed addition of nerve growth factor to ciliary neurotrophic factor-supported cultures at 14 days for a further seven days fails to induce choline acetyltransferase immunoreactivity in these p75NGFR-positive septal neurons. In cultures grown in the continual presence of nerve growth factor from plating, removal of nerve growth factor and addition of nerve growth factor antibodies at 14 days results in the death of over 80% of the cholinergic neurons after a further four days. Addition of ciliary neurotrophic factor during the period of nerve growth factor withdrawal appears to preserve a p75NGFR-positive, choline acetyltransferase-negative neuronal population. However, seven day re-addition of nerve growth factor to ciliary neurotrophic factor-treated, nerve growth factor-withdrawn cultures fails to induce choline acetyltransferase immunoreactivity in the ciliary neurotrophic factor-supported p75NGFR-positive septal neurons. Simultaneous treatment of cultures with both ciliary neurotrophic factor and nerve growth factor for 14 days from plating approximately doubles the number of p75NGFR-positive neurons relative to cultures treated with either ciliary neurotrophic factor or nerve growth factor alone, but the number of choline acetyltransferase-positive neurons in these cultures is not significantly greater than that found in cultures treated solely with nerve growth factor. These results suggest that ciliary neurotrophic factor does not support the survival and differentiation of developing septal cholinergic neurons in vitro, but can support the development of a p75NGFR-immunoreactive population of non-cholinergic septal neurons.
 ...
PMID:Ciliary neurotrophic factor supports p75NGFR-immunoreactive non-cholinergic, but not cholinergic, developing septal neurons in vitro. 765 10

The effects of transforming growth factor alpha (TGF alpha) on low and high density cultures of fetal (embryonic day 17) rat medial septal cells were investigated and in some instances, compared to those of epidermal growth factor (EGF). In high density cultures, TGF alpha induces a significant increase in the number of astroglia and microglia. While the effects of TGF alpha on the astroglia are more pronounced when compared to EGF, those on the microglia are less notable. In addition, TGF alpha produces a time- and dose-dependent decrease in the activity of choline acetyltransferase (EC 2.3.1.6) and a proportional decrease in the number of acetylcholinesterase-positive neurons in these high density cultures. However, although both EGF and TGF alpha decreased choline acetyltransferase activity maximally at the same concentration (10 ng/ml), the latter was consistently more potent. TGF alpha does not affect cholinergic cell survival but the expression of their chemical phenotype and does so indirectly via the glial cells. On the other hand, TGF alpha directly induces a dose- and time-dependent increase in glutamic acid decarboxylase activity in these high density cultures without affecting the number of glutamic acid decarboxylase immunoreactive neurons. In low density cultures, TGF alpha acts as a general neuronal survival factor, affecting both cholinergic and GABAergic neurons. Here TGF alpha's neurotrophic activity is more evident than its effects on their chemical phenotype. These results suggest that TGF alpha exerts distinct and differential effects on the biochemical expression of two neuronal populations in the developing medial septum maintained in high density culture. Finally, as TGF alpha acts as a general neuronal survival factor in low density cultures, cell to cell interactions appear to be important in the ultimate response of these cells to this growth factor.
 ...
PMID:Transforming growth factor alpha differentially affects GABAergic and cholinergic neurons in rat medial septal cell cultures. 886 17

Lesions of the basal forebrain deplete the neocortex of cholinergic fibers. Acetylcholine depletion in the somatosensory cortex of rats results in reduced stimulus-evoked activity in response to whisker stimulation. Previous studies demonstrate that embryonic basal forebrain transplants improve functional activity toward normal. It is not clear if the activity increase is due to cholinergic replacement or other factors present in the graft. In this study, we examined the possibility that nerve growth factor (NGF), a neurotrophin known as a survival factor and a specific protectant for cholinergic basal forebrain neurons, can preserve basal forebrain cells after a lesion and restore functional activity in the somatosensory cortex. We report that NGF alone is capable of restoring functional activity in the barrel cortex of animals with basal forebrain lesions, while vehicle injections of saline do not alter activity. Both high (10 microg) and low (5 microg) doses of NGF unilaterally injected into the lateral ventricle improved stimulus-evoked functional activity during bilateral whisker stimulation. The mechanism of NGF action is not clear since the restoration of functional activity in cortex was not accompanied by increased cholinergic activity as detected by acetylcholinesterase fiber staining. NGF may act directly on cortical neurons, although its site of action is not well defined.
 ...
PMID:Nerve growth factor increases stimulus-evoked metabolic activity in acetylcholine-depleted barrel cortex. 1044 63