Coexistence of choline acetyltransferase and nerve growth factor receptors in the rat basal forebrain

Dawbarn, David; Allen, Shelley J; Semenenko, F. M.

doi:10.1016/0304-3940(88)90284-4

Cited by 102 publications

(36 citation statements)

References 28 publications

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“…To test this hypothesis, and recognizing the limitations inherent in the interpretation of data obtained from heterogeneous cellular models, we profiled the transcriptome of purified septal cholinergic neurons. These cells are amenable to purification by FACS because Ͼ90% of them express NGFR and, similarly, Ͼ90% of NGFR-expressing cells are cholinergic (10,11). Moreover, the adult-like pattern of septal NGFR-expressing cells is established by E17 in the rat (12).…”

Section: Resultsmentioning

confidence: 99%

Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons

López-Coviella

Follettie

Mellott

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Basal forebrain cholinergic neurons (BFCN) participate in processes of learning, memory, and attention. Little is known about the genes expressed by BFCN and the extracellular signals that control their expression. Previous studies showed that bone morphogenetic protein (BMP) 9 induces and maintains the cholinergic phenotype of embryonic BFCN. We measured gene expression patterns in septal cultures of embryonic day 14 mice and rats grown in the presence or absence of BMP9 by using species-specific microarrays and validated the RNA expression data of selected genes by immunoblot and immunocytochemistry analysis of their protein products. BMP9 enhanced the expression of multiple genes in a time-dependent and, in most cases, reversible manner. The set of BMP9-responsive genes was concordant between mouse and rat and included genes encoding cell-cycle͞growth control proteins, transcription factors, signal transduction molecules, extracellular matrix, and adhesion molecules, enzymes, transporters, and chaperonins. BMP9 induced the p75 neurotrophin receptor (NGFR), a marker of BFCN, and Cntf and Serpinf1, two trophic factors for cholinergic neurons, suggesting that BMP9 creates a trophic environment for BFCN. To determine whether the genes induced by BMP9 in culture were constituents of the BFCN transcriptome, we purified BFCN from embryonic day 18 mouse septum by using fluorescence-activated cell sorting of NGFR ؉ cells and profiled mRNA expression of these and NGFR ؊ cells. Approximately 30% of genes induced by BMP9 in vitro were overexpressed in purified BFCN, indicating that they belong to the BFCN transcriptome in situ and suggesting that BMP signaling contributes to maturation of BFCN in vivo.nerve growth factor receptor ͉ neuronal development ͉ septum ͉ microarray ͉ fluorescence-activated cell sorting B one morphogenetic proteins (BMPs) play critical roles in the development of the nervous system, and there is growing evidence that BMPs regulate the expression of neurotransmitter phenotype, including the cholinergic phenotype (1-4) of basal forebrain cholinergic neurons (BFCN) that project to the neocortex and hippocampus and are important in the processes of attention, learning, and memory (5). Previous studies identified multiple BMP-regulated target genes in a variety of cells, including nervous tissue. However, although BMP target genes have been characterized in the specification of catecholaminergic and serotonergic neurons (6, 7), little is known about BMP target genes implicated in BFCN determination. BFCN are defined by their neuroanatomical location and the neurotransmitter that they synthesize and release, i.e., acetylcholine. The latter process requires a concerted expression of three genes, encoding choline acetyltransferase (Chat), the vesicular acetylcholine transporter (Vacht), and the choline transporter 1 (Cht1). Several additional features of these cells include expression of acetylcholinesterase, the neurotrophin receptors NGFR and TRKA, the expression of certain neurotransmitter receptors (...

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Section: Resultsmentioning

confidence: 99%

Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons

López-Coviella

Follettie

Mellott

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Many basal forebrain neurons express the low-a¤nity receptor p75 NTR Springer et al, 1987) as well as the high-a¤nity NGF receptor TrkA (Steininger et al, 1993). Almost all neurons expressing NGF receptors are also positive for the cholinergic marker ChAT (p75 NTR : Dawbarn et al, 1988;Batchelor et al, 1989;TrkA: Sobreviela et al, 1994). In the cerebral cortex, axons that express p75 NTR (Pioro and Cuello, 1990) and TrkA (Sobreviela et al, 1994;Hu et al, 1997) probably arise from the basal forebrain, and basal forebrain neurons retrogradely transport NGF exogenously applied to cortex (Seiler and Schwab, 1984;Domenici et al, 1994b).…”

Section: Local Cortical Ngf Infusion Increases the Number Of Basal Fomentioning

confidence: 99%

“…Finally, cortical administration of antibodies against either p75 NTR (Taniuchi et al, 1986) or TrkA (Pizzorusso et al, 1999) results in retrograde transport of the antibodies to cells in the basal forebrain. It seems unlikely that the NGF-induced increase in NGF-like immunoreactivity in basal forebrain neurons is due to synthesis of NGF by these neurons, since almost all of the basal forebrain neurons that express NGF receptors are ChAT-positive (p75 NTR : Dawbarn et al, 1988;Batchelor et al, 1989;TrkA: Sobreviela et al, 1994), while none of the basal forebrain neurons that express NGF mRNA are cholinergic (Lauterborn et al, 1995). However, intraventricular injections of NGF increase the expression of mRNA for p75 NTR (Higgins et al, 1989), TrkA (Holtzman et al, 1992), and ChAT (Higgins et al, 1989) in basal forebrain neurons, and this could also lead to increased levels of protein expression in the cell bodies of these neurons.…”

Section: Increased Protein Expression or Retrograde Transport?mentioning

confidence: 99%

“…Assuming that the e¡ects of NGF on protein expression are mediated by the NGF receptors TrkA and/or p75 NTR , neurons that do not express NGF receptors on their axon terminals would be unable to respond to exogenous NGF. Since those basal forebrain neurons that normally express NGF receptors almost always express ChAT as well (p75 NTR : Dawbarn et al, 1988;Batchelor et al, 1989;TrkA: Sobreviela et al, 1994), the increase in ChAT-positive neurons after cortical NGF infusion probably occurred in a population that was already expressing ChAT at lower levels prior to the NGF delivery.…”

Section: Increased Protein Expression or Retrograde Transport?mentioning

confidence: 99%

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Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development

Silver¹,

Fagiolini²,

Gillespie³

et al. 2001

Neuroscience

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AbstractöIntracerebroventricular or intracortical administration of nerve growth factor (NGF) has been shown to block or attenuate visual cortical plasticity in the rat. In cats and ferrets, the e¡ects of exogenous NGF on development and plasticity of visual cortex have been reported to be small or nonexistent. To determine whether locally delivered NGF a¡ects ocular dominance column formation or the plasticity produced by monocular deprivation in cats at the height of the critical period, we infused recombinant human NGF into the primary visual cortex of kittens using an implanted cannula minipump. NGF had no e¡ect on the normal developmental segregation of geniculocortical a¡erents into ocular dominance columns as determined both physiologically and anatomically. The plasticity of binocular visual cortical responses induced by monocular deprivation was also normal in regions of immunohistochemically detectable NGF infusion, as measured using intrinsic signal optical imaging and single-unit electrophysiology. Immunohistochemical analysis of the basal forebrain regions of the same animals demonstrated that the NGF infused into cortex was biologically active, producing an increase in the number of NGF-, TrkA-, p75 NTR -, and choline acetyltransferase-positive neurons in basal forebrain nuclei in the hemisphere ipsilateral to the NGF minipump compared to the contralateral basal forebrain neurons.We conclude that NGF delivered locally to axon terminals of cholinergic basal forebrain neurons resulted in increases in protein expression at the cell body through retrograde signaling. ß 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.Key words: TrkA, p75, choline acetyltransferase, retrograde transport, acetylcholine, monocular deprivation.Monocular deprivation (MD) is a well-studied model of experience-dependent cortical plasticity. When one eye of an animal is occluded during a critical period of development, that eye loses most of its ability to drive neurons in primary visual cortex, shifting the distribution of visual responses to favor the nondeprived eye (Wiesel and Hubel, 1963). Intracerebroventricular (ICV) administration of the neurotrophin nerve growth factor (NGF) to rats during a critical period of development blocks the e¡ects of MD (Domenici et al., 1991;Ma¡ei et al., 1992). This has been demonstrated at several levels of analysis, including physiological, anatomical, immunocytochemical, and behavioral (for a review, see Cellerino and Ma¡ei, 1996). Infusion of NGF directly into developing rat visual cortex also prevents physiological ocular dominance plasticity (Lodovichi et al., 2000).In addition, anti-NGF antibodies prevent normal anatomical and physiological development of the visual system when they are administered to rats by implantation of antibody-secreting hybridoma cells in the lateral ventricle (Berardi et al., 1994). These antibodies also prolong the critical period for ocular dominance plasticity in the rat (Domenici et al., 1994a). Together, these results demonstrate an imp...

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“…Thus, a map of high-affinity NGF binding sites in brain will identify the most likely neuronal targets for the neurotrophic actions of NGF. The distribution of NGF receptors (NGFRs) in brain has been studied with emulsion autoradiography using an iodinated murine NGFR (mu-NGFR) antibody (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) or 1251-muNGF (15)(16)(17)(18)(19) as ligands.…”

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confidence: 99%

Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain.

Altar¹,

Burton²,

Bennett³

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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MATERIALS AND METHODSProduction, Purification, and lodination of rhNGF. Purified (>98%) rhNGF was produced by the Research Collaborations group at Genentech, using transfected Chinese hamster ovary cell cultures and anion-exchange chromatography (25) as described (26,27). rhNGF stimulated PC12 (rat pheochromocytoma cell line) neurite outgrowth (51) with an EC50 value of 39 and 52 pg/ml in two experiments conducted by different personnel in separate laboratories (Fig. 1). rhNGF was iodinated (28) with modifications (26, 27) and used within 1-6 days in all but one study, since decreases in the proportion of total 1251-rhNGF binding that was displaced by 100 nM rhNGF were noted after this time. Two-and 3-week-old uCi/,ug; 3580 Ci/mmol of rhNGF dimer; 1 Ci = 37 GBq) stimulated neurite outgrowth in the PC12 bioassay with an EC50 of 49 ± 19 pg/ml (2-week-old tracer; n = 4) and 49 ± 0.8 pg/ml (3-week-old tracer; n = 3). The 1-day-old batch of tracer produced a half-maximal stimulation of PC12 neurite outgrowth at 35 pg/ml. Without a biochemical separation of labeled and unlabeled species, we cannot exclude the possibility that biological activity is due to unlabeled rhNGF. However, the high degree of rhNGF labeling (1.65:1 ratio of 1251 to rhNGF dimer), the retrograde transport of 125I-rhNGF, which can be blocked by rhNGF (26), and the indistinguishable potencies of rhNGF and 125I-rhNGF in the PC12 assay (Fig. 1) indicate that 1251_ rhNGF is active in bioassays of NGF function.Brain Sections. Brains from male Sprague-Dawley rats were frozen in isopentane at -15°C either separately, for anatomical mapping, or as a group of four to five brain hemispheres (22), for association, dissociation, and equilibrium saturation analyses. Sections (12 ,um) were thawmounted onto gelatin-coated glass microscope slides and stored frozen for up to 1 month at -70°C.

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Coexistence of choline acetyltransferase and nerve growth factor receptors in the rat basal forebrain

Cited by 102 publications

References 28 publications

Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons

Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons

Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development

Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain.

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