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1.
Nerve growth factor gene expression in the developing rat brain 总被引：31，自引：0，他引：31
T H Large S C Bodary D O Clegg G Weskamp U Otten L F Reichardt 《Science (New York, N.Y.)》1986,234(4774):352-355
The regulation of nerve growth factor (NGF) protein and NGF messenger RNA (mRNA) in the developing rat brain has been studied to assess the hypothesis that NGF supports the differentiation of cholinergic neurons in the basal forebrain. In the adult, the major targets of these neurons, the hippocampus and neocortex, contain the highest concentrations of NGF mRNA, but comparatively low ratios of NGF protein to its mRNA. In contrast, a high concentration of NGF protein and a low concentration of NGF mRNA were seen in the basal forebrain, consistent with retrograde transport of NGF protein into this region from the neocortex and hippocampus. In these two target regions NGF and NGF mRNA were barely detectable at birth, their concentrations increased to a peak at day 21, and then NGF mRNA, but not NGF protein, declined threefold by day 35. NGF accumulation in the basal forebrain paralleled that in the target regions and preceded an increase in choline acetyltransferase, suggesting that the differentiation of cholinergic projection neurons is indeed regulated by retrogradely transported NGF. In addition, high ratios of NGF protein to NGF mRNA, comparable to that in the basal forebrain, were seen in the olfactory bulb and cerebellum, suggesting that NGF may be transported into these regions by unidentified neurons. 相似文献
2.
Expression of the beta-nerve growth factor gene in hippocampal neurons 总被引：16，自引：0，他引：16
C Ayer-LeLievre L Olson T Ebendal A Seiger H Persson 《Science (New York, N.Y.)》1988,240(4857):1339-1341
In situ hybridization with complementary DNA probes for nerve growth factor (NGF) was used to identify cells containing NGF messenger RNA in rat and mouse brain. The most intense labeling occurred in hippocampus, where hybridizing neurons were found in the dentate gyrus and the pyramidal cell layer. The neuronal identity of NGF mRNA-containing cells was further assessed by a loss of NGF-hybridizing mRNA in hippocampal areas where neurons had been destroyed by kainic acid or colchicine. RNA blot analysis also revealed a considerable decrease in the level of NGF mRNA in rat dentate gyrus after a lesion was produced by colchicine. This lesion also caused a decrease in the level of Thy-1 mRNA and an increase in the level of glial fibrillary acidic protein mRNA. Neuronal death was thus associated with the disappearance of NGF mRNA. These results suggest a synthesis of NGF by neurons in the brain and imply that, in hippocampus, NGF influences NGF-sensitive neurons through neuron-to-neuron interactions. 相似文献
3.
Molecular cloning of a gene sequence regulated by nerve growth factor 总被引：22，自引：0，他引：22
Nerve growth factor (NGF) is essential for the development and differentiation of sympathetic or sensory neurons. A complementary DNA was cloned that corresponds to a gene sequence induced more than 50-fold in a cultured target cell line of pheochromocytoma cells (PC12 cells) 5 hours after the addition of NGF. The induced messenger RNA encodes a 90,000-dalton polypeptide that may represent one of the primary events in NGF-induced differentiation of neurons. 相似文献
4.
Choline acetyltransferase activity in striatum of neonatal rats increased by nerve growth factor 总被引：35，自引：0，他引：35
W C Mobley J L Rutkowski G I Tennekoon K Buchanan M V Johnston 《Science (New York, N.Y.)》1985,229(4710):284-287
Some neurodegenerative disorders may be caused by abnormal synthesis or utilization of trophic molecules required to support neuronal survival. A test of this hypothesis requires that trophic agents specific for the affected neurons be identified. Cholinergic neurons in the corpus striatum of neonatal rats were found to respond to intracerebroventricular administration of nerve growth factor with prominent, dose-dependent, selective increases in choline acetyltransferase activity. Cholinergic neurons in the basal forebrain also respond to nerve growth factor in this way. These actions of nerve growth factor may indicate its involvement in the normal function of forebrain cholinergic neurons as well as in neurodegenerative disorders involving such cells. 相似文献
5.
Neurotrophic factors 总被引：22，自引：0，他引：22
In addition to nerve growth factor (NGF), many proteins present in soluble tissue extracts and in the extracellular matrix influence the survival and development of cultured neurons. The structure, synthesis, and mechanism of action of NGF as a neurotrophic factor are considered along with the experiments on the new putative trophic molecules. 相似文献
6.
Induction by NGF of meiotic maturation of Xenopus oocytes expressing the trk proto-oncogene product. 总被引：16，自引：0，他引：16
A R Nebreda D Martin-Zanca D R Kaplan L F Parada E Santos 《Science (New York, N.Y.)》1991,252(5005):558-561
The effect of nerve growth factor (NGF) was assessed in Xenopus oocytes expressing the human trk proto-oncogene product, p140prototrk. Oocytes injected with trk messenger RNA expressed polypeptides recognized by antibodies to the trk gene product. Exposure of these oocytes to nanomolar amounts of NGF resulted in specific surface binding of 125I-labeled NGF, tyrosine phosphorylation of p140prototrk, and meiotic maturation, as determined by germinal vesicle breakdown and maturation promoting factor (p34cdc2) kinase activation. Thus the trk proto-oncogene product can act as a receptor for NGF in a functionally productive manner. 相似文献
7.
Chimeric NGF-EGF receptors define domains responsible for neuronal differentiation 总被引：15，自引：0，他引：15
To determine the domains of the low-affinity nerve growth factor (NGF) receptor required for appropriate signal transduction, a series of hybrid receptors were constructed that consisted of the extracellular ligand-binding domain of the human epidermal growth factor (EGF) receptor (EGFR) fused to the transmembrane and cytoplasmic domains of the human low-affinity NGF receptor (NGFR). Transfection of these chimeric receptors into rat pheochromocytoma PC12 cells resulted in appropriate cell surface expression. Biological activity mediated by the EGF-NGF chimeric receptor was assayed by the induction of neurite outgrowth in response to EGF in stably transfected cells. Furthermore, the chimeric receptor mediated nuclear signaling, as evidenced by the specific induction of transin messenger RNA, an NGF-responsive gene. Neurite outgrowth was not observed with chimeric receptors that contained the transmembrane domain from the EGFR, suggesting that the membrane-spanning region and cytoplasmic domain of the low-affinity NGFR are necessary for signal transduction. 相似文献
8.
Nerve growth factor treatment after brain injury prevents neuronal death 总被引：47，自引：0，他引：47
L F Kromer 《Science (New York, N.Y.)》1987,235(4785):214-216
Cholinergic neuronal degeneration after axotomy has been proposed to be due to the loss of a retrogradely transported neurotrophic factor, possibly nerve growth factor (NGF). To test this hypothesis, NGF was continuously infused into the lateral ventricles of adult rats that had received bilateral lesions of all cholinergic axons projecting from the medial septum to the dorsal hippocampus. After 2 weeks of NGF treatment, identification of cholinergic neurons by the presence of the biosynthetic enzyme choline acetyltransferase revealed a dramatic increase (350%) in the survival of the axotomized septal cholinergic neurons. Thus, NGF or an NGF-like molecule can act as a neurotrophic factor for these neurons. 相似文献
9.
Deppmann CD Mihalas S Sharma N Lonze BE Niebur E Ginty DD 《Science (New York, N.Y.)》2008,320(5874):369-373
We report that developmental competition between sympathetic neurons for survival is critically dependent on a sensitization process initiated by target innervation and mediated by a series of feedback loops. Target-derived nerve growth factor (NGF) promoted expression of its own receptor TrkA in mouse and rat neurons and prolonged TrkA-mediated signals. NGF also controlled expression of brain-derived neurotrophic factor and neurotrophin-4, which, through the receptor p75, can kill neighboring neurons with low retrograde NGF-TrkA signaling whereas neurons with high NGF-TrkA signaling are protected. Perturbation of any of these feedback loops disrupts the dynamics of competition. We suggest that three target-initiated events are essential for rapid and robust competition between neurons: sensitization, paracrine apoptotic signaling, and protection from such effects. 相似文献
10.
Localization of amyloid beta protein messenger RNA in brains from patients with Alzheimer's disease 总被引：43，自引：0，他引：43
S Bahmanyar G A Higgins D Goldgaber D A Lewis J H Morrison M C Wilson S K Shankar D C Gajdusek 《Science (New York, N.Y.)》1987,237(4810):77-80
The distribution of cells containing messenger RNA that encodes amyloid beta protein was determined in hippocampi and in various cortical regions from cynomolgus monkeys, normal humans, and patients with Alzheimer's disease by in situ hybridization. Both 35S-labeled RNA antisense and sense probes to amyloid beta protein messenger RNA were used to ensure specific hybridization. Messenger RNA for amyloid beta protein was expressed in a subset of neurons in the prefrontal cortex from monkeys, normal humans, and patients with Alzheimer's disease. This messenger RNA was also present in the neurons of all the hippocampal fields from monkeys, normal humans and, although to a lesser extent in cornu ammonis 1, patients with Alzheimer's disease. The distribution of amyloid beta protein messenger RNA was similar to that of the neurofibrillary tangles of Alzheimer's disease in some regions, but the messenger RNA was also expressed in other neurons that are not usually involved in the pathology of Alzheimer's disease. 相似文献
11.
Superinduction of c-fos by nerve growth factor in the presence of peripherally active benzodiazepines 总被引：66，自引：0，他引：66
Alterations in proto-oncogene expression after stimulation of rat pheochromocytoma (PC12) cells by nerve growth factor (NGF) have been investigated. A specific stimulation of c-fos messenger RNA and protein was detected 30 minutes after treatment. This induction was enhanced more than 100-fold in the presence of peripherally active benzodiazepines. The effect was specific as very little change was observed in the levels of c-rasHa, c-rasKi, c-myc, and N-myc messenger RNA's. Under the conditions used here, NGF treatment ultimately results in neurite outgrowth, with a reduction or cessation of cell division. Thus, stimulation of the c-fos gene in this system appeared to be associated with differentiation and not with cellular proliferation. The effect of benzodiazepines was stereospecific and represents a novel action of these compounds at the level of gene expression. 相似文献
12.
An anti-apoptotic role for the p53 family member, p73, during developmental neuron death 总被引：1，自引：0，他引：1
Pozniak CD Radinovic S Yang A McKeon F Kaplan DR Miller FD 《Science (New York, N.Y.)》2000,289(5477):304-306
p53 plays an essential pro-apoptotic role, a function thought to be shared with its family members p73 and p63. Here, we show that p73 is primarily present in developing neurons as a truncated isoform whose levels are dramatically decreased when sympathetic neurons apoptose after nerve growth factor (NGF) withdrawal. Increased expression of truncated p73 rescues these neurons from apoptosis induced by NGF withdrawal or p53 overexpression. In p73-/- mice, all isoforms of p73 are deleted and the apoptosis of developing sympathetic neurons is greatly enhanced. Thus, truncated p73 is an essential anti-apoptotic protein in neurons, serving to counteract the pro-apoptotic function of p53. 相似文献
13.
14.
A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor 总被引：136，自引：0，他引：136
J Milbrandt 《Science (New York, N.Y.)》1987,238(4828):797-799
15.
J T Elder G J Fisher P B Lindquist G L Bennett M R Pittelkow R J Coffey L Ellingsworth R Derynck J J Voorhees 《Science (New York, N.Y.)》1989,243(4892):811-814
Transforming growth factor alpha (TGF-alpha) is produced by and required for the growth of epithelial cells and is angiogenic in vivo. Since epidermal hyperplasia and angiogenesis are hallmarks of psoriasis, TGF-alpha gene expression was analyzed in epidermal biopsies of normal and psoriatic skin. TGF-alpha messenger RNA and protein are much more abundant in lesional psoriatic epidermis than in normal-appearing skin of psoriatic patients or in normal epidermis. In contrast, messenger RNA levels of transforming growth factor beta 1 (TGF-beta 1), which inhibits epithelial cell growth, are not significantly different in normal, uninvolved, and lesional psoriatic epidermis. Thus, psoriatic epidermal hyperplasia may involve increased expression of a keratinocyte mitogen (TGF-alpha) rather than deficient expression of a growth inhibitor (TGF-beta 1). 相似文献
16.
Grafting genetically modified cells to the damaged brain: restorative effects of NGF expression 总被引：18，自引：0，他引：18
M B Rosenberg T Friedmann R C Robertson M Tuszynski J A Wolff X O Breakefield F H Gage 《Science (New York, N.Y.)》1988,242(4885):1575-1578
Fibroblasts were genetically modified to secrete nerve growth factor (NGF) by infection with a retroviral vector and then implanted into the brains of rats that had surgical lesions of the fimbria-fornix. The grafted cells survived and produced sufficient NGF to prevent the degeneration of cholinergic neurons that would die without treatment. In addition, the protected cholinergic cells sprouted axons that projected in the direction of the cellular source of NGF. These results indicate that a combination of gene transfer and intracerebral grafting may provide an effective treatment for some disorders of the central nervous system. 相似文献
17.
Neuronal properties of clonal hybrid cell lines derived from central cholinergic neurons 总被引：5，自引：0，他引：5
Clonal cell lines derived from specific types of central neurons can be used to identify and characterize properties specific to those neurons. With somatic cell fusion techniques, nine clonal hybrid cell lines have been developed from the septal region of the mouse basal forebrain. Two lines express characteristics typical of cholinergic neurons--choline acetyltransferase activity and immunoreactivity, neurite formation with neurofilament protein immunoreactivity, and aggregation in rotation-mediated cell culture. These cell lines may be useful for studying the trophic interactions that support the development and maintenance of central cholinergic connections. 相似文献
18.
AIDS-Kaposi's sarcoma-derived cells express cytokines with autocrine and paracrine growth effects 总被引：51，自引：0，他引：51
B Ensoli S Nakamura S Z Salahuddin P Biberfeld L Larsson B Beaver F Wong-Staal R C Gallo 《Science (New York, N.Y.)》1989,243(4888):223-226
When grown in vitro, cells from Kaposi's sarcoma lesions of AIDS patients (AIDS-KS cells) constitutively release several growth promoting activities. When inoculated into nude mice, the AIDS-KS cells induce a KS-like lesion of mouse origin. Here it is shown that the AIDS-KS cells express messenger RNA for a complex mixture of cytokines that correlate with several of the biological activities of these cells. Basic fibroblast growth factor, which is a potent angiogenic factor, and interleukin-1 messenger RNAs are expressed at very high levels and seem to account for a large proportion of the activities, since their corresponding proteins are released in biologically active form into the culture media where they induce autocrine and paracrine growth effects. 相似文献
19.
K Muegge T M Williams J Kant M Karin R Chiu A Schmidt U Siebenlist H A Young S K Durum 《Science (New York, N.Y.)》1989,246(4927):249-251