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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cholinergic pathway ascending from the nucleus basalis magnocellularis (NBM) to the cortex has been implicated in several important higher brain functions such as learning and memory. Following infarction of the frontoparietal cortical area in the rat, a retrograde atrophy of cholinergic cell bodies and fiber networks occurs in the basalocortical cholinergic system. We have observed that neuronal atrophy in the NBM induced by this lesion can be prevented by intracerebroventricular administration of exogenous nerve growth factor (NGF) or the monosialoganglioside GM1. In addition, these agents can upregulate levels of cortical choline acetyltransferase (ChAT) activity in the remaining cortex adjacent to the lesion site. Furthermore, an enhancement in cortical high-affinity 3H-choline uptake and a sustained in vivo release of cortical acetylcholine (ACh) after K+ stimulation are also observed after the application of neurotrophic agents. Moreover, these biochemical changes in the cortex are accompanied by an anatomical remodeling of cortical ChAT-immunoreactive fibers and their synaptic boutons.
Mol Neurobiol 1992
PMID:Trophic factor effects on cholinergic innervation in the cerebral cortex of the adult rat brain. 128 34

Steady state levels of the mRNA coding for the neurotransmitter biosynthetic enzyme, acetylCoA-choline-O-acetyltransferase (ChAT, EC 2.3.1.6), were measured in wild type Drosophila and two temperature-sensitive mutants (Chats1 and Chats2) using the RNase protection method. At a permissive temperature the relative amounts of ChAT mRNA were: wild type: Chats1:Chats2 = 1:2.09 (+/- 0.39):3.37 (+/- 0.57) (mean +/- S.E.M.) indicating that mutant flies may compensate, for making a thermolabile form of enzyme, by producing and/or maintaining higher levels of ChAT mRNA. At a restrictive temperature the ChAT mRNA levels decreased in both mutants and increased in wild type flies. The regulatory mechanism(s) responsible for increasing ChAT mRNA in wild type flies appears to have failed in the mutants at high temperature. Steady state mRNA levels were also measured in embryonic cell cultures prepared from wild type embryos. Cultures grown in the presence of two pharmacologic agents (carbamylcholine and d-tubocurarine) which should interfere with cholinergic neurotransmission, showed less mRNA resulting from a decrease in levels of ChAT gene transcription. Our results imply that neurotransmission and the rate of neurotransmitter biosynthetic enzyme gene transcription are coupled for the cholinergic system in Drosophila.
Brain Res Mol Brain Res 1992 Apr
PMID:Positive and negative feedback regulation of choline acetyltransferase mRNA levels in Drosophila: a study using temperature-sensitive mutants and embryo cell cultures. 131 95

The effect of nerve growth factor (NGF) on muscarinic receptor subtypes was investigated in a primary culture of telencephalic neurons prepared from neonatal rats. The treatment with 100 ng/ml of NGF significantly enhanced choline acetyltransferase (ChAT) activity and intracellular acetylcholine (ACh) content during cultivation. The same treatment induced an early transient increase of the number of muscarinic cholinergic receptors (mAChR), as measured by [3H]quinuclidinyl benzilate binding to cell homogenate, that was followed by a dramatic decrease of the receptor density from the 9th day of culture. Atropine completely prevented the decrease of the maximal number of muscarinic recognition sites induced by NGF. Prolonged exposure of telencephalic neurons to NGF also induced a significant reduction of the relative content of the messenger RNA (mRNA) encoding m1 and m3 receptors, while the m4 transcript was increased by the treatment. We suggest that the prolonged stimulation of cholinergic neurons by NGF induces a downregulation of m1 and m3 mAChR and their mRNAs on the postsynaptic site, while it increases the synthesis of the functionally distinct m4 receptor subtype, which might be presynaptically localized on cholinergic neurons. The transient increase of the receptor number that occurs at the first days of culture was not paralleled by changes in the relative content of mAChR mRNAs and might be associated with the trophic activity of NGF on cholinergic synapses during early development.
Brain Res Mol Brain Res 1992 Aug
PMID:Nerve growth factor modulates the expression of muscarinic cholinergic receptor messenger RNA in telencephalic neuronal cultures from newborn rat brain. 132 97

We have used a polyclonal antibody raised against a synthetic peptide from the carboxyl terminal of the beta-amyloid precursor protein (APP) to examine the cellular and subcellular localization of this protein in the rat brain. Light and electron microscopic immunocytochemical techniques were used. Immunoreactivity was found throughout the brain in all the neurons examined as well as in oligodendrocytes. At the light microscopic level, a perinuclear filamentous distribution was seen in neurons, suggesting a concentration of the protein to the Golgi apparatus. Axotomy of motor neurons of the facial nucleus produced a decrease in choline acetyltransferase (ChAT) activity and an increase in the perineuronal microglial nucleoside diphosphatase (NDPase)-positive cells in addition to a hypertrophy of the GFAP immunoreactive astrocytes. On the other hand, increased APP-like immunoreactivity all over the neuronal cell bodies accompanied by a dispersion ('rete dispersion') of the Golgi apparatus labeling was demonstrated. In contrast, reactive microglia and hypertrophic astrocytes in axotomized facial nucleus were not immunolabeled. Oligodendrocytes showed a punctate APP immunoreactivity corresponding to the Golgi apparatus in both operated and control facial nucleus. This was further demonstrated by electron microscopic immunolabeling. These results show that the main localization of the C-terminal containing forms of the APP in the rat brain is the Golgi apparatus in both neurons and oligodendroglia and further supporting the secretory nature of these proteins. The increased synthesis of this protein after axotomy is suggestive of a role of the APPs in growth and/or regeneration.
Brain Res Mol Brain Res 1992 Oct
PMID:Beta-amyloid precursor protein localization in the Golgi apparatus in neurons and oligodendrocytes. An immunocytochemical structural and ultrastructural study in normal and axotomized neurons. 133 76

The effects of peripherally administered thyroid hormone (TH; 500 micrograms/kg; i.p.; q.d.) on the relative abundances of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) RNA were determined by rtPCR in the cortex and hippocampus of young adult rats. Corresponding changes in choline acetyltransferase (ChAT) activity were measured since NGF and BDNF have been shown to enhance the expression of this marker enzyme of central cholinergic pathways. Abundance levels of NGF and NT-3, relative to cyclophilin (cycl), were increased significantly (+50%, P < 0.05) in the hippocampus following TH treatment. Despite enhanced abundance of NGF in the hippocampus, ChAT activity was unchanged, whereas ChAT activity was modestly increased by 28% in the cortex without corresponding changes in NGF, NT-3 or BDNF. These results demonstrate that TH administration is capable of inducing the accumulation of NT-3, in addition to NGF but that the induction levels of RNA cannot be directly correlated with responsivity of the cholinergic system as measured by ChAT activity.
Brain Res Mol Brain Res 1992 Dec
PMID:Thyroid hormone regulation of NGF, NT-3 and BDNF RNA in the adult rat brain. 133 33

Complementary DNA (cDNA) clones containing the entire coding region of human choline acetyltransferase (ChAT) were isolated from cDNA libraries prepared from the autopsied spinal cord. In the human cDNA, the ATG codon assigned to the putative initiation codon for pig, rat and mouse ChAT cDNAs was replaced by ACG. The human cDNA contained an in-frame ATG codon 324 nucleotides upstream of the ACG codon. Therefore, human ChAT cDNA should code for a 748 amino acid polypeptide of 82.6 kDa. This deduced molecular weight was larger than that of ChAT protein purified from the human brain and placenta (64-70 kDa). The human ChAT cDNA containing the entire coding region was ligated to an expression vector and introduced into African green monkey kidney (COS) cells and Chinese hamster ovary (CHO) cells. The cells expressed high ChAT activity and produced two protein bands immunostained with an antibody to monkey ChAT. The molecular weight of the proteins was estimated to be approximately 70 and 80 kDa by polyacrylamide-SDS gel electrophoresis. When partial cDNAs that lacked the first ATG but contained the replaced ACG codon were introduced into COS cells, the cells expressed moderate ChAT activity and an immunoreactive protein band of 70 kDa. These results indicate that translation of human ChAT mRNA starts at two sites and produces two enzyme proteins with different molecular weights. It might be that the larger form of ChAT molecule is an enzyme precursor for processing or that the N-terminal extrapeptide is needed for subcellular localization of the enzyme.
Brain Res Mol Brain Res 1992 Dec
PMID:A complementary DNA for human choline acetyltransferase induces two forms of enzyme with different molecular weights in cultured cells. 133 37

In the present study the acute effect of intravenous aluminum chloride (1 mg/kg) on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities of rats was investigated. Aluminum was found to cross the blood-brain barrier (BBB) as indicated by the detection of aluminum in the cerebrospinal fluid (CSF) 30 min after femoral vein injection. Two hours following aluminum injection, ChAT activity in the basal forebrain and hippocampus was significantly reduced by 30% and 22%, respectively, whereas no change was observed in the caudate nuclei. On the other hand, AChE activity was significantly increased by 45% in the caudate nuclei, whereas little change was observed in other brain areas. This report demonstrates that rapid transport of Al across the BBB, and the acute nature of Al neurotoxicity in rats.
Mol Chem Neuropathol 1992 Aug
PMID:Aluminum-induced acute cholinergic neurotoxicity in rat. 138 51

1. The localization of choline acetyltransferase messenger RNA has been studied using a digoxigenin-tailed complementary oligodeoxynucleotide probe for in situ hybridization. 2. Putative cholinergic cells of the rat and ferret spinal cord and the ferret retina were labeled. 3. This technique affords superior resolution compared to radioactively labeled probes, with apparently equal sensitivity.
Cell Mol Neurobiol 1992 Aug
PMID:Choline acetyltransferase expression studied with an oligonucleotide probe. 139 69

The polymerase chain reaction (PCR) was used to develop a method for detection and relative quantification of the choline acetyltransferase (ChAT) mRNA in neonatal and adult rat CNS. Oligonucleotide primers derived from a porcine ChAT cDNA sequence were used in coupled reverse transcriptase (RT)-PCR to amplify a cDNA sequence of 206 bp which arises in a cycle- and RNA-dependent manner and which hybridizes with both an internal oligonucleotide and a ChAT cDNA probe. ChAT mRNA was detected in spinal cord, septal area, striatum, cortex and hippocampus but not in cerebellum and cardiac or skeletal muscle. In the septal area, relative quantitative evaluation of ChAT mRNA levels by RT-PCR indicates that this transcript is developmentally regulated and increased following intracerebral administration of nerve growth factor (NGF) to both neonatal and young adult rats. This suggests that the increases of ChAT activity observed in basal forebrain during development or after NGF administration are, at least in part, associated with an increase in corresponding levels of mRNA.
Brain Res Mol Brain Res 1991 Mar
PMID:Choline acetyltransferase messenger RNA expression in developing and adult rat brain: regulation by nerve growth factor. 164 35

1. In situ hybridization histochemical techniques in combination with immunocytochemistry and acetylcholinesterase (AChE) histochemistry were used to study the colocalization of messenger RNA (mRNA) encoding the neuropeptide substance P (SP) in cholinergic cells of the laterodorsal tegmental nucleus (LDT) of the rat pontine brain stem. 2. Alternate serial sections were hybridized with a 48-base, 35S-labeled synthetic oligonucleotide probe encoding SP using in situ hybridization histochemistry and processed either histochemically for AChE or immunocytochemically for choline acetyltransferase (ChAT). 3. In addition, serial section analysis was used to demonstrate the correlation between SP and SP mRNA in the same cells of the LDT. 4. These studies reveal that the cholinergic neurons of the LDT synthesize SP.
Cell Mol Neurobiol 1990 Mar
PMID:Localization of substance P mRNA in cholinergic cells of the rat laterodorsal tegmental nucleus: in situ hybridization histochemistry and immunocytochemistry. 169 61


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