Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies established that fetal rat and human neuropeptide Y (NPY) cortical neurons in aggregate cultures are differentially regulated. Whereas brain-derived neurotrophic factor (BDNF) or phorbol 12-myristate-13-acetate (PMA) induces NPY production in rat cultures, only PMA does so in human cultures. We addressed these questions: 1) Do soluble products of rat or human astrocytes (conditioned medium; rCM and hCM, respectively) enhance the functional expression of cultured NPY neurons and if so, do they enhance the expression of somatostatin (SRIF) neurons as well? 2) Is the NPY-enhancing activity (EA) in the CM species specific? rCM enhanced (approximately 2-fold) both basal and BDNF-stimulated production of NPY and coculture of rat aggregates and astrocytes did not prevent this NPY-EA. Likewise, the hCM enhanced (approximately 2.5-fold) basal and PMA-stimulated production of NPY by human aggregates. Moreover, the hCM enhanced NPY production by rat aggregates and rCM enhanced NPY production by human aggregates. In addition, rCM and hCM each enhanced BDNF-, forskolin-, or PMA-stimulated NPY production by rat aggregates. Under each of the above conditions, the rCM/hCM suppressed (approximately 50%) production of SRIF by rat aggregates. In summary, secretory products of rat and human astrocytes exert opposite effects on the functional expression of NPY and SRIF neurons in culture: enhancement of NPY and suppression of SRIF. By the criteria evaluated in this study, these astrocyte-derived activities do not exhibit species specificity.
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PMID:Opposite effects of astrocyte-derived soluble factor(s) on the functional expression of fetal peptidergic neurons in aggregate cultures: enhancement of neuropeptide Y and suppression of somatostatin. 940 22

Changes in the expression of somatostatin (SRIF) have been observed in the brains of HIV encephalitis. Since gp120 is thought to play a major role in AIDS-associated abnormalities in the brain, we addressed the question: Does gp120 alter the functional expression of human fetal SRIF neurons in culture and if so, is this effect fetal-age dependent? Aggregate cultures, obtained from cortices of nine fetuses (14.9-20.7 weeks), were exposed for 7 days to BDNF or BDNF+gp120; BDNF induced production of SRIF during the subsequent 24-48 h was assessed. Similar effects of BDNF and gp120 were observed in the 9 brain-cultures. A 7-day exposure to BDNF alone led to a significant increase in SRIF production (p=0.014), whereas exposure to gp120 alone did not. Co-exposure to BDNF and gp120 led to an increase in BDNF-induced SRIF production which was significantly greater than that after BDNF alone (p=0.006). These effects were BDNF- and gp120-dose dependent and they were not accompanied by changes in DNA content of the aggregates nor in lactate dehydrogenase activity in the medium; indicating that gp120 did not lead to a major loss of cell integrity. These results are consistent with a synergistic effect of BDNF and gp120 leading to enhanced functional expression of the signalling pathway(s) mediating BDNF induction of SRIF production; an effect expressed by fetal brains throughout the 2nd trimester of gestation. Thus, this culture system can serve as a model to study the mechanism(s) underlying the early interactions between gp120 BDNF in the developing human brain.
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PMID:Evidence for a synergistic effect of the HIV-1 envelope protein gp120 and brain-derived neurotrophic factor (BDNF) leading to enhanced expression of somatostatin neurons in aggregate cultures derived from the human fetal cortex. 987 21

Although neurotrophins (NTs) have been extensively studied as neuronal survival factors in some areas of the central nervous system, little is known about their function or cellular targets in the hypothalamus. To understand their functional significance and sites of action on hypothalamic neurons, we examined the effects of their cognate ligands on neuropeptide content and messenger RNA (mRNA) expression in somatostatin neurons present in fetal rat hypothalamic cultures. Treatments were performed in defined insulin-free medium between days 6 and 8 of culture, since the maximal effects of NTs on somatostatin content and mRNA expression were observed after 48-h incubations. Brain-derived neurotrophic factor and NT-3, but not nerve growth factor, induced a dose-dependent increase in somatostatin content, which was influenced by plating density. The same treatment increased somatostatin mRNA and immunostaining intensity of somatostatin neurons, but had no effect on the number of these labeled neurons. The increased levels of somatostatin (peptide and mRNA) induced by NTs were not blocked by tetrodotoxin or by glutamate receptor antagonists, suggesting that endogenous neurotransmitters (e.g. glutamate) were not involved in these effects. In contrast, the stimulatory effects were completely blocked by K-252a, an inhibitor of tyrosine kinase (Trk) receptors, whereas the less active analog K-252b was ineffective. Double-labeling studies demonstrated that both TrkB or TrkC receptors were located on somatostatin neurons. Our results show that, in rat hypothalamic cultures, brain-derived neurotrophic factor, and NT-3 have a potent stimulatory effect on peptide synthesis in somatostatinergic neurons, likely through direct activation of TrkB and TrkC receptors.
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PMID:Brain-derived neurotrophic factor and neurotrophin-3 enhance somatostatin gene expression through a likely direct effect on hypothalamic somatostatin neurons. 992 23

Sensitivity to the pungent vanilloid, capsaicin, defines a subpopulation of primary sensory neurons that are mainly polymodal nociceptors. The recently cloned vanilloid receptor subtype 1 (VR1) is activated by capsaicin and noxious heat. Using combined in situ hybridization and histochemical methods, we have characterized in sensory ganglia the expression of VR1 mRNA. We show that this receptor is almost exclusively expressed by neurofilament-negative small- and medium-sized dorsal root ganglion cells. Within this population, VR1 mRNA is detected at widely varying levels in both the NGF receptor (trkA)-positive, peptide-producing cells that elicit neurogenic inflammation and the functionally less characterized glial cell line-derived neurotrophic factor-responsive cells that bind lectin Griffonia simplicifolia isolectin B4 (IB4). Cells without detectable levels of VR1 mRNA are found in both classes. A subpopulation of the IB4-binding cells that produce somatostatin has relatively low levels of VR1 mRNA. A previously uncharacterized population of very small cells that express the receptor tyrosine kinase (RET) and that do not label for trkA or IB4-binding has the highest relative levels of VR1 mRNA. The majority of small visceral sensory neurons of the nodose ganglion also express VR1 mRNA, in conjunction with the BDNF receptor trkB but not trkA. Axotomy results in the downregulation of VR1 mRNA in dorsal root ganglion cells. Our data emphasize the heterogeneity of VR1 mRNA expression by subclasses of small sensory neurons, and this may result in their differential sensitivity to chemical and noxious heat stimuli. Our results also indicate that peripherally derived trophic factors may regulate levels of VR1 mRNA.
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PMID:Differential expression of the mRNA for the vanilloid receptor subtype 1 in cells of the adult rat dorsal root and nodose ganglia and its downregulation by axotomy. 1002 68

The mammalian visual cortex contains morphologically diverse populations of interneurons whose neurochemical properties are believed to be regulated by neurotrophic factors. This requires the expression of neurotrophin receptors. We have analysed whether brain-derived neurotrophic factor (BDNF), its receptor trkB and the NT-3 receptor trkC are expressed in interneurons of rat visual cortex in vivo, and in organotypic visual cortex cultures, paying particular attention to the subsets of neuropeptidergic neurons. In situ hybridization in combination with immunofluorescence for calcium-binding proteins and neuropeptides revealed that BDNF is not expressed in interneurons in vivo or in vitro. For the neurotrophin receptors we found in vivo at postnatal day 70 (P70) that approximately 80% of the parvalbumin-immunoreactive (-ir), but only 50% of the intensely calbindin-ir, and only 20% of the calretinin-ir neurons express trkB. Double labelling with neuropeptides revealed that approximately 50% of the neuropeptide Y-ir and approximately 50% of the somatostatin-ir neurons express trkB in a laminar-specific way. Only 25% of the vasoactive intestinal polypeptide (VIP)-ir neurons coexpress trkB. The coexpression of neuropeptide Y with trkB, but not with BDNF or trkC, was confirmed with a double in situ hybridization. In contrast, the percentages differed in the immature cortex; at P14 70% of the NPY-ir neurons and 46% of the calretinin-ir neurons revealed trkB expression, while the ratio for calbindin-ir cells was fairly constant (59%). From the interneuron populations studied, only 12% of the parvalbumin-ir neurons expressed trkC. A triple labelling revealed that some neurons coexpressed both trk mRNAs, while others had only trkC. The analysis of interneurons in organotypic cultures yielded very similar results. The results indicate that trkB ligands synthesized by pyramidal neurons influence neuropeptide or calcium-binding protein expression in a paracrine or transsynaptic manner. However, in contrast to current belief, in the adult only about half of all interneurons appear responsive to trkB ligands. Although the proportion is higher in the immature cortex, not all of the interneurons appear neurotrophin-receptive. With regard to the presence or absence of neurotrophin receptors, the molecular heterogeneity of GABAergic interneurons in the visual cortex is higher than currently assumed, and the responsiveness to neurotrophins changes with development in a cell type-specific way.
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PMID:Expression of TrkB and TrkC but not BDNF mRNA in neurochemically identified interneurons in rat visual cortex in vivo and in organotypic cultures. 1010 14

Neuropeptide protein levels in hippocampal interneurons exhibit a considerable maturation in postnatal animals. This study characterizes the role of neuronal activity in determining neuropeptide protein levels in postnatal hippocampal interneurons, and the involvement of neurotrophins. In hippocampal slices from 7-day-old rats cultured for 2 weeks, treatment with the gamma-aminobutyric acidA (GABAA) receptor antagonist bicuculline increased the staining intensity and the number of neurons immunoreactive for neuropeptide Y (NPY). An opposite effect was observed when non-N-methyl-d-aspartate (non-NMDA) excitatory transmission was blocked. The effects of either treatment were reversed after return to control medium. These findings were similar to those previously obtained on the effects of activity on somatostatin immunostaining. Blockade of endogenous tyrosine kinase neurotrophin receptors using K252a prevented the effects of bicuculline on NPY- and somatostatin-immunoreactive neurons. Application of exogenous neurotrophin-3 (NT-3) increased NPY and somatostatin protein levels in long-term but not short-term cultures, while nerve growth factor (NGF) had no effect. In contrast, brain-derived neurotrophic factor (BDNF) or neurotrophin-4 (NT-4) did not affect equally NPY and somatostatin immunoreactivity: they mimicked the effects of bicuculline treatment on NPY-immunoreactive neurons, but exerted no conspicuous effect on somatostatin immunostaining. These results indicate that although neuronal activity plays a major role in determining neuropeptide protein levels in postnatal hippocampal interneurons, its effects on different neuropeptides might be exerted through different mechanisms, with or without the mediation of BDNF or NT-4.
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PMID:BDNF and NT-4 differentiate two pathways in the modulation of neuropeptide protein levels in postnatal hippocampal interneurons. 1021 18

Using a double detection method, which combines in situ hybridization for the detection of neurotrophin messenger RNA with immunocytochemistry against the neuropeptides somatostatin, neuropeptide Y, vasoactive intestinal polypeptide and cholecystokinin, we have analysed the expression of the neurotrophins, nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3, in distinct populations of neuropeptide-immunoreactive hippocampal interneurons. Nerve growth factor messenger RNA expression was found in subsets of the four subpopulations of neuropeptide-immunoreactive interneurons. The highest degree of co-localization was observed in the neuropeptide-Y-positive cells (up to 70%) and in somatostatin-immunoreactive cells (48%). Only small subsets of cholecystokinin- and vasoactive intestinal polypeptide-positive neurons (21% and 10%, respectively) displayed nerve growth factor hybridization signals. In contrast, expression of neurotrophin-3 messenger RNA was exclusively observed in 26% of neuropeptide-Y-immunoreactive cells. Brain-derived neurotrophic factor hybridization signals were never detected in the neuropeptide-positive hippocampal interneurons. Morphological analysis of neuropeptide-immunoreactive interneurons that express or lack nerve growth factor messenger RNA revealed that most perisomatic inhibitory neurons, such as large vasoactive intestinal polypeptide/ cholecystokinin-immunoreactive cells, showed positive nerve growth factor hybridization signals. In addition, some somatostatin/neuropeptide-Y-immunoreactive interneurons, which are responsible for dendritic inhibition of principal hippocampal neurons, expressed nerve growth factor messenger RNA. In contrast, interneurons specialized to innervate other GABAergic cells, such as small vasoactive intestinal polypeptide-positive cells, lacked nerve growth factor expression. All these data indicate that expression of neurotrophins is differentially regulated in functionally distinct classes of hippocampal interneurons immunoreactive for neuropeptides. We also analysed whether neuropeptide-immunoreactive interneurons expressing neurotrophins were targets of the GABAergic septohippocampal pathway. We used a triple detection method, combining anterograde tracing of this connection, with in situ hybridization for the detection of neurotrophin mRNA, and immunocytochemistry against neuropeptides. Our data showed that the four populations of hippocampal interneurons studied (somatostatin, neuropeptide-Y, vasoactive intestinal polypeptide and cholescystokinin) received GABAergic afferents from the septum. However, no preference for neuropeptide-immunoreactive cells expressing neurotrophins was observed, compared to neuropeptide-positive neurons lacking neurotrophin expression.
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PMID:Expression of neurotrophins in hippocampal interneurons immunoreactive for the neuropeptides somatostatin, neuropeptide-Y, vasoactive intestinal polypeptide and cholecystokinin. 1036 97

Moscona, in the early sixties [A.A. Moscona, Recombination of dissociated cells and the development of cell aggregates, in: B.M. Willmer (Ed.), Cells and Tissues in Culture, Academic Press, New York, 1965, pp. 489-529.] [16], discovered that aggregation of dissociated cells is a property of embryonal cells. Several features of the aggregate culture system are particularly attractive for the conduct of biochemical and molecular studies on the human fetal brain. (i) All the pertinent procedural parameters can be readily controlled and standardized, resulting in a consistently reproducible system suitable for quantitative analyses. (ii) Neuronal enriched aggregates can be readily obtained, with minimal neurotoxicity. (iii) Aggregates can be easily harvested for biochemical and molecular studies. Aggregate cultures, generated from rodent fetal brains, have been extensively utilized as a tool to study regulation of aminergic neurons [P. Honegger, E. Richelson, Biochemical differentiation of mechanically dissociated brain in aggregating cell culture, Brain Res. 109 (1976) 335-354; P. Honegger, E. Richelson, Biochemical differentiation of aggregating cell cultures of different fetal rat brain regions, Brain Res. 133 (1977) 329-339.] [11,12] and peptidergic neurons (neuropeptide Y (NPY) and somatostatin (SRIF) [A. Barnea, E. Anthony, G. Lu, G. Cho, Morphological differentiation of neuropeptide Y neurons in aggregate cultures of dissociated fetal cortical cells: a model system for glia-neuron paracrine interactions, Brain Res. 625 (1993) 313-322; A. Barnea, G. Cho, G. Lu, M. Mathis, Brain-derived neurotrophic factor induces functional expression and phenotypic differentiation of cultured fetal neuropeptide Y producing neurons, J. Neurosci. Res. 42 (1995) 638-647; A. Barnea, A. Hajibeigi, G. Cho, P. Magni, Regulated production and secretion of immunoreactive neuropeptide Y by aggregating fetal brain cells in culture, Neuroendocrinology 54 (1991) 7-13; P. Magni, A. Barnea, Forskolin and phorbol ester stimulation of neuropeptide Y (NPY) production and secretion by aggregating fetal brain cells in culture: evidence for regulation of NPY biosynthesis at transcriptional and posttranscriptional levels, Endocrinology 130 (1992) 976-984.]) [4-6,14]. However, very few studies have utilized this system to study regulatory processes of human fetal neurons/glia [M. McCarthy, L. Resnik, F. Taub, R.V. Stewart, R.D. Dix, Infection of human neural cell aggregate cultures with a clinical isolate of cytomegalovirus, J. Neuropathol. Exp. Neurol. 50 (1991) 441-450; L. Pulliam, M.E. Berens, M.L. Rosenblum, A normal human brain cell aggregate model for neurobiological studies, J. Neurosci. Res. 21 (1988) 521-530.] [15,17]. In a series of studies in our laboratory [N. Aguila-Mansilla, A. Barnea, Human fetal brain cells in aggregate culture: a model system to study regulatory processes of the developing human neuropeptide Y (NPY) producing neuron, Int. J. Dev. Neurosci. 14 (1996) 531-539; A. Barnea, N. Aguila-Mansilla, H.T. Chute, A.A. Welcher, Comparison of neurotrophin regulation of human and rat neuropeptide Y (NPY) neurons: induction of NPY production in aggregate cultures derived from rat but not from human fetal brains, Brain Res. 732 (1996) 52-60; A. Barnea, N. Aguila-Mansilla, G. Lu, R.H. Ho, Opposite effects of astrocyte-derived soluble factor(s) on the functional expression of fetal peptidergic neurons in aggregate cultures: enhancement of neuropeptide Y and suppression of somatostatin, J. Neurosci. Res. 50 (1997) 605-617; A. Barnea, J. Roberts, R.H. Ho, Evidence for a synergistic effect of the HIV-1 envelope protein gp120 and brain-derived neurotrophic factor (BDNF) leading to enhanced expression of somatostatin neurons in aggregate cultures derived from the human fetal cortex, Brain Res. 815 (1999) 349-357.] [1-3,7], we have established a human-derived aggregate culture system, maintained in serum-free medium for up to 28 days, in which expression
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PMID:An improved method for dissociation and aggregate culture of human fetal brain cells in serum-free medium. 1044 10

We have previously demonstrated that, in the adult mouse, injection of kainate/AMPA receptors agonists into the dorsal hippocampus induces major structural modifications of the dentate gyrus granule cells. Such changes are mediated by the brain-derived neurotrophic factor (BDNF). Considering previous involvements of BDNF in activity-linked regulations of hippocampal neuronal phenotype, changes of neurochemical contents were further investigated. It is shown that excitatory granule cells rapidly acquire a strong immunoreactivity for the inhibitory neurotransmitters GABA and neuropeptide-Y, with different patterns for both molecules. GABA immunoreactivity appeared first in mossy fibers, before extending to cell bodies and dendrites. Analysis of glutamic acid decarboxylase revealed slight increases in mossy fibers and no somatic labeling. In contrast to GABA, neuropeptide-Y labeling was observed first in granule cell soma and then in mossy fibers, with a centrifugal gradient. All labelings were transient, but slight amounts of GABA and NPY were kept in some cell bodies for at least 6 months. Confocal microscope analysis of double GABA/NPY labelings revealed colocalization of both mediators in the same neurons. The specificity of kainate-linked changes was suggested by lack of immunoreactivity for somatostatin. These results show that the capacities of mature granule cells to adapt environmental modifications can concern neurochemical contents, by synthesis and/or uptake of specific molecules. The fact that adaptive changes are rapid and transient suggests a direct response to kainate, in order to limit its potentially deleterious effects. Colocalization of GABA and neuropeptide-Y indicates that the dentate gyrus granule cells can use several pathways to this aim.
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PMID:Excitatory granule cells of the dentate gyrus exhibit a double inhibitory neurochemical content after intrahippocampal administration of kainate in adult mice. 1048 76

Although the long-lasting effects of neurotrophins have been extensively studied, less data are available on their rapid effects, especially on peptide release. In the present report, we investigated rapid effects of neurotrophins on somatostatin release and on intracellular calcium concentration ([Ca(2+)](i)) in primary cultures of hypothalamic neurons. RT-PCR experiments revealed mRNA expression of the three high-affinity neurotrophin receptors tyrosine kinase (Trk) TrkA, TrkB and TrkC, indicating potential responses to their preferential ligands: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3), respectively. We demonstrated that BDNF, and to a lesser extent NT-3, induced significant time- and concentration-dependent somatostatin release, while NGF was devoid of any effect. BDNF or NT-3 induction of somatostatin release was inhibited by the Trk inhibitors K-252a and genistein, whereas K-252b, a less effective inhibitor, had no effect. BDNF- and NT-3-induced somatostatin release depended upon extra- and intracellular Ca(2+) since it was completely abolished in the presence of the Ca(2+) chelators BAPTA (bis-(alpha-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid) or BAPTA-AM (bis-(alpha-aminophenoxy)-ethane-N,N,N',N'-tetraacetoxymethylester), respectively. In addition, BDNF and NT-3 induced a sustained and rapid increase in [Ca(2+)](i) which depended on the extracellular Ca(2+) concentration. MK-801 (dizocilpine) and tetrodotoxin (TTX) entirely blocked neurotrophin-evoked somatostatin release and [Ca(2+)](i) rise in response to BDNF and NT-3 application in most neurons. Neurotrophin-induced [Ca(2+)](i) rise was completely blocked by K-252a. The present results are consistent with: (1) an indirect effect of neurotrophins on somatostatin release via endogenous glutamate release and subsequent NMDA receptor activation, (2) a major indirect effect of neurotrophins on Ca(2+) rise in hypothalamic neurons which very likely occurs through NMDA receptor activation. Taken altogether, these results indicate that BDNF and NT-3 can rapidly affect the activity of hypothalamic neurons.
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PMID:Rapid stimulatory effects of brain-derived neurotrophic factor and neurotrophin-3 on somatostatin release and intracellular calcium rise in primary hypothalamic cell cultures. 1143 57


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