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Results for “trans-synaptic signaling”

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At least 19 recordsLinked to original sources
PubMed1994

Regulation of bFGF gene expression and subcellular distribution of bFGF protein in adrenal medullary cells.

Basic fibroblast growth factor (bFGF), a potent mitogenic/neurotrophic factor, controls the development and plasticity of many types of neural cells. In adrenal chromaffin cells, the appearance of bFGF protein coincided with the establishment of functional innervation, suggesting induction by trans-synaptic signals. In cultured bovine adrenal medullary cells Western blot analysis revealed 18-, 23-, and 24-kD bFGF isoforms in the cytosolic and nuclear fractions. Stimulation of acetylcholine nicotinic receptors or hormonal angiotensin II receptors or the direct stimulation of adenylate cyclase with forskolin or protein kinase C (PKC) with PMA increased the content of all bFGF isoforms. Increases in the levels of intracellular bFGF did not result in detectable presence of bFGF proteins in culture medium. Instead, bFGF proteins accumulated in the cytoplasm or the nucleus depending on whether PKC or cAMP pathways were activated. The long-term nuclear forskolin-induced accumulation of bFGF was prevented by cycloheximide or by antisense bFGF oligonucleotide and was also accompanied by an increase in bFGF mRNA. We used luciferase reporter plasmids containing the human bFGF promoter to show that the induction of bFGF resulted from transcriptional activation of the bFGF gene and was mediated by regulatory sequences located upstream from its transcription start site. Stimulation of bFGF gene expression by forskolin and PMA was synergistic and was mediated through different promoter regions. The results suggest that stimulation by cAMP and PKC is mediated through novel cis elements. The regulation of bFGF protein content also involves posttranscriptional mechanisms since changes in the levels of individual bFGF isoforms were different depending on whether cells were treated with carbachol or angiotensin II, forskolin, or PMA. The present study indicates that bFGF is an intracrine cytoplasmic-nuclear factor, whose expression is regulated by trans-synaptic and hormonal stimuli and which may act as a direct mediator of genomic responses to afferent stimulation.

Adrenal Medulla↗
PubMed1992

Insect systems for the study of programmed neuronal death.

In the moth Manduca sexta and the fly Drosophila melanogaster, the emergence of the adult is followed by a period of neuronal death. The steroid hormones, the ecdysteroids, are involved in two aspects of this death. Ecdysteroid action early in metamorphosis is somehow essential for fixing the fates of the neurons that will die. The actual triggering of their death, however, occurs a few weeks later and requires the withdrawal of the steroid and, at least in some cases, a trans-synaptic signal. These "execution" events involve both RNA and protein synthesis and result in the onset of degeneration about 10 h later. The early "decision" of a neuron to opt for the degeneration fate is associated with an altered pattern of ecdysteroid receptor expression. A model is presented to relate how the levels of steroid receptors may be related to the activation of death-related genes.

Animals↗
PubMed2026

Estimating protein isoform abundances with [Formula: see text].

A single gene can encode multiple versions of a protein, dubbed isoforms, with varying functionality. Cellular control of isoform abundances is critical for multiple aspects of biology and is only partially regulated by transcript levels. While long-read sequencing facilitates transcript quantification, quantifying the resulting protein isoforms on a large scale is a major challenge, complicating biological interpretation of transcript alterations. Standard "bottom up" mass spectrometry can assess only short portions of isoforms called peptides, and these peptides often map onto more than one isoform. We introduce [Formula: see text] (Protein isoform Abundance Quantification), a Bayesian method that leverages multiomic information from the peptidome and transcriptome to provide accurate estimates of isoform abundance even when peptide mapping is ambiguous. [Formula: see text] offers several advantages over existing methods in a unified framework. It provides uncertainty quantification, integrates multiomic information for improved accuracy, and provides a rigorous framework for hypothesis testing. Extensive simulations show that [Formula: see text] consistently outperforms competing methods in detecting differentially abundant protein isoforms and estimating their abundances. We use [Formula: see text] to investigate differences in isoform abundance levels between people with schizophrenia and control subjects, confirming a long-held hypothesis that levels of the C4A isoform of Complement Component 4 are increased in schizophrenia while C4B is not. These results demonstrate that [Formula: see text] can identify significant variations in isoform abundance levels not previously possible.

Protein Isoforms↗
PubMed1983

The role of prostaglandins in neuroendocrine junctions: studies in the pineal gland and the hypothalamus.

This article discusses current experimental evidence indicating a role for prostaglandins (PGs) in pineal and median eminence neuroendocrine junctions. Both tissues release PGs, particularly of the E series, upon exposure to norepinephrine (NE) and through alpha-adrenoceptors. Exposure of pineal and median eminence explants to nanomolar concentrations of PGE2 augments melatonin and GnRH release, respectively. In the pineal gland, this effect appears to be linked to the stimulation of adenylate cyclase. Both in vivo and in vitro PG synthesis inhibitors impair the hormone release elicited by NE. In the pineal gland, PGE2 also constitutes a trans-synaptic negative signal for NE release. PGs receptors are present in pineal and hypothalamic membranes.

Animals↗
PubMed1989

Expression of dopaminergic phenotypes in the mouse olfactory bulb induced by the calcitonin gene-related peptide.

In the olfactory bulb, tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamines, is expressed after birth when the axons of olfactory epithelial neurons have made synapses in the bulb. It has been suggested that expression of TH is regulated trans-synaptically because on deafferentation of the bulb there is a marked decrease in the contents of TH, dopamine and 3,4-dihydroxyphenylacetic acid, which, however, return to normal levels after regeneration of the primary afferents. To date the molecular signalling involved in this trans-synaptic induction has not yet been characterized; I have therefore studied the expression of dopaminergic properties (presence of TH and dopamine uptake) in dissociated cell cultures from embryonic mouse olfactory bulb. I report that the number of dopaminergic cells increases fivefold when olfactory bulb neurons are co-cultured with olfactory epithelial neurons and that soluble factors, rather than cell interactions, mediate this effect. The dopaminergic-inducing factor is the calcitonin gene-related peptide (CGRP) which is present in chemosensory neurons of the olfactory epithelium and when added at nanomolar concentrations to olfactory bulb cultures mimics the effect of olfactory epithelial neurons. Significantly the induction of dopaminergic phenotypes brought about by olfactory epithelial neurons is abolished by an antiserum to CGRP. These observations show that CGRP is involved in the differentiation of dopaminergic olfactory bulb neurons.

Animals↗
PubMed1995

Co-localization of NOS and NMDA receptor in esophageal premotor neurons of the rat.

Nitric oxide (NO) production following NMDA receptor stimulation plays a role in signaling between neurons. Using trans-synaptic tracing with pseudorabies virus (PRV), immunocytochemistry and histochemistry, we have demonstrated the expression of NMDAR1 and nitric oxide synthase (NOS) within brain stem neurons controlling esophageal peristalsis. PRV-immunoreactive second order esophageal premotor neurons of the central subnucleus of the nucleus of the solitary (NTScen) expressed NMDAR1 and NOS. First order motoneurons of the compact formation of the nucleus ambiguus (NAc) expressed NMDAR1, but did not contain NOS. NTScen neurons may synthesize and release NO in response to NMDA activation, suggesting a role for NO in the coordination of esophageal motility.

Animals↗
PubMed1980

[Axonal transport from the nerve ending to the nerve cell body: a pathway for trophic signals and neurotoxins].

Nerve cells with their very long axons and dendrites have an effective system of anterograde and retrograde transport. In the retrograde direction there is, in addition to endogeneous cell constituents, a substantial transport of exogenous material like e.g. trophic factors like NGF. We have found that molecules which bind with high affinity to receptors in the nerve teminal surface membranes (e.g. NGF, tetanus and cholera toxin, lectins) are selectively internalized and transported retrogrdely to the cell body. Although most of them are incorporated into lysosomes in the cell body, they can nevertheless exert specific signal functions in the cell (NGF). Tetanus toxin, however, is released by the dendrites and transferred trans-synaptically to higher order neurons. We suggest that this retrograde and trans-synaptic transport represents an important pathway for "trophic" signal molekules, which convey information from the target cells to the innervating neurons. The same pathways can be used by neurotoxins *tetanus toxin) and neurotrophic viruses for entering the nervous system.

Animals↗
PubMed1992

Trans-synaptic regulation of gene expression.

Neurotransmitters regulate gene expression through second messenger cascades that transmit the signal from the plasma membrane to the nucleus of the postsynaptic cell. Ca2+ and cAMP are two of the second messengers that regulate gene expression in response to neurotransmitters. The Ca2+ and cAMP signals induce expression of a class of genes, termed immediate early genes, within minutes of neurotransmitter receptor activation. Many of these genes encode transcription factors that regulate the expression of late response genes. The results of recent experiments have elucidated mechanisms by which neurotransmitter-induced Ca2+ and cAMP signals regulate immediate early gene expression.

Animals↗
PubMed1988

A common trans-acting factor is involved in transcriptional regulation of neurotransmitter genes by cyclic AMP.

Activation of neurotransmitter receptors can regulate transcription in postsynaptic cells through the actions of second messengers. Trans-synaptic regulation of transcription appears to be an important mechanism controlling the synthesis of molecules involved in neuronal signaling, especially neuropeptides. Proenkephalin, vasoactive intestinal polypeptide, and somatostatin have been shown to be transcriptionally regulated by the second messenger, cyclic AMP (cAMP), as has the catecholamine synthesizing enzyme tryosine hydroxylase. cAMP-inducible elements have been mapped within these genes, and trans-acting factors which bind to several such elements have been identified. With the discovery that individual neurons generally contain multiple transmitters within their synaptic terminals, it has become important to understand in detail the mechanisms by which the synthesis of transmitters can be coregulated. Here we compare the structure and function of the proenkephalin cAMP-inducible enhancer with the mapped cAMP-inducible elements of the vasoactive intestinal polypeptide, somatostatin, and tyrosine hydroxylase genes and a putative cAMP-inducible element in the proto-oncogene c-fos. We have previously shown that the proenkephalin enhancer is composed of two different elements, ENKCRE-1 and ENKCRE-2. We show here that one of these, ENKCRE-2, is structurally similar to elements found within the vasoactive intestinal polypeptide, somatostatin, and tyrosine hydroxylase genes and binds a trans-acting factor that is competed for both in cotransfection experiments (in vivo) and in DNase I footprint assays (in vitro) by these other elements. The c-fos element has similar structural requirements to confer transcriptional induction by cAMP but competes less strongly. Protein purified by affinity chromatography with the ENKCRE-2 sequence binds to each of these elements. A second element within the proenkephalin cAMP-inducible enhancer, ENKCRE-1, binds a factor that is not competed for by these other genes and is therefore distinct. This analysis suggests a potential mechanism of transcriptional coregulation of the neuronally expressed genes investigated in this study and also demonstrates that multiple factors are involved in transcriptional activation by cAMP.

Binding, Competitive↗
PubMedDate not supplied

Pharmacology of neuronal gene expression.

Pharmacological treatments were used to estimate trans-synaptic regulation of opioid peptide gene expression occuring at specific neurotransmitter receptors. In vitro and in vivo studies have shown that different signal-transduction mechanisms regulate the transcription of proenkephalin, proopiomelanocortin and nerve growth factor mRNA. The activation of receptors coupled to adenylate cyclase elicited the increase of proenkephalin and nerve growth factor gene expression. Therefore, a cAMP-dependent mechanism was suggested to be involved in such regulation. However, the temporal delay between the elevation of the intracellular cAMP content and the increase in nerve growth factor and proenkephalin mRNAs prompted us to investigate whether additional mechanisms associated with the second messenger were operative in the regulation of the expression of these two genes. We report evidence that a protein(s), probably functioning as a trans-acting factor, might be involved in the regulation of nerve growth factor gene transcription. The characterization and isolation of these DNA regulatory proteins will provide the pharmacologist with valuable information for the development of new compounds in the therapy of mental disorders.

Animals↗
PubMed1989

Neurons of the striate cortex driven trans-synaptically by electrical stimulation of the superior colliculus.

The latencies of trans-synaptic responses in cells of the striate cortex, following electrical stimulation in the superior colliculus, were evaluated to assess the possible path taken by the neural signal. Most of the recorded striate neurons were judged to be driven by the signal passing back along the axons and then into the collaterals of cortico-tectal cells in lamina 5. The present results indicate that striate neurons, in communicating with the superior colliculus, at the same time, send signals via their collaterals to neighbouring cells in lamina 5 which appear to have similar C or complex receptive fields.

Animals↗
PubMed1989

Preproenkephalin gene expression in the rat spinal cord after noxious stimuli.

The trans-synaptically activated biosynthesis of the preproenkephalin (PPE) mRNA in the dorsal horn of the rat lumbar spinal cord was examined by an in situ hybridization histochemical technique. As a nociceptive stimulus, a small amount of formalin was injected into the right hindpaw, and quantitative and qualitative changes of PPE-mRNA expression were determined by emulsion autoradiography. Formalin injection was found to result in a significant increase in the number and signal intensity of neurons expressing PPE-mRNAs in the superficial and deep layers of the ipsilateral spinal dorsal horn. Expression of PPE-mRNA increased within 1 h after formalin injection in neurons of deep layers, but gradually for at least 24 h in neurons in the superficial layers. These results at the level of the spinal cord showed that differential responses of PPE neurons related to the pain sensation occurred trans-synaptically after nociceptive stimulation applied to the periphery.

Animals↗
PubMed1992

Neurotransmitter-stimulated immediate-early gene responses are organized through differential post-synaptic receptor mechanisms.

The products of the cellular immediate-early genes (IEGs) are thought to act as messengers in the coupling of trans-synaptic stimuli with altered neuronal gene expression. However, the manner in which neurotransmission specifies particular responses through the IEGs is undefined. In this report, mRNA and transcription analysis of a precisely-timed, physiological IEG response illustrates how an IEG signal may be organized through differential neurotransmitter receptor activation. The nocturnal pattern of IEG expression in the rat pineal gland has been shown to be differentially regulated through post-synaptic adrenergic receptors. Induction of the c-fos gene is primarily mediated through alpha 1-receptors, whereas the coordinately regulated jun-B gene exhibits dual regulation through alpha 1- and beta-receptors. A simultaneous repression of c-jun expression is partly mediated through a beta-receptor mechanism. In vitro analysis of IEGs in cultured pineal glands has confirmed the receptor-specific link between adrenergic neurotransmission and IEG induction. The pineal is a unique neuroendocrine model in which the characteristics and function of the IEG third messenger system may be defined.

Animals↗
PubMed1994

A daily rhythm of activator protein-1 activity in the rat pineal is dependent upon trans-synaptic induction of JunB.

The daily cycle of phenotypic variation in the mammalian pineal provides a unique model for the investigation of the molecular mechanisms that regulate neurotransmitter synthesis. In the rat, a circadian adrenergic mechanism directs a change in serotonin metabolism that results in the nocturnal production of melatonin. Activity of the activator protein-1 transcriptional regulatory complex, as demonstrated by band-shift assays of rat pineal gland extracts, has now been shown to exhibit a rhythm, in vivo, which is temporally correlated with the rhythm of melatonin synthesis. Thus, nocturnal activator protein-1 activity (23.00 h) is markedly elevated, being 8-fold higher than the level of light-phase activity (P < 0.005). The nocturnal activator protein-1 protein complex is induced through a trans-synaptic, beta-adrenoceptor-linked mechanism and is characterized by the prolonged participation of JunB as demonstrated using antibodies for specific activator protein-1 proteins. Indeed, JunB appears to be a major component of nocturnal changes in activator protein-1 activity, JunD forming an additional, constitutive component which is not affected by the nocturnal adrenergic signal. The alpha 1-adrenoreceptor-linked c-Fos protein, which is coordinately induced with JunB, does not form a stable component of nocturnal activator protein-1 activity. In contrast, parallel experiments showed that c-Fos does form a major component of the hippocampal activator protein-1 complex that is induced in rats following kainic acid treatment. In the pineal, a similar, although not identical, pattern of activator protein-1 activation has also been demonstrated in cultured glands following treatment with norepinephrine. Immunoblotting has demonstrated parallel accumulation of JunB and c-Fos protein in pineal nuclear fractions following stimulation both in vivo and in vitro. The results provide evidence of posttranscriptional selection of neurotransmitter-stimulated activator protein-1 protein complexes, a mechanism which complements the differential induction of fos and jun genes in the pineal, and serves to generate a specific activator protein-1 transcription factor complex. This finding has general implications for the functional interpretation of fos and jun gene induction in neuronal systems. The stable JunB complex demonstrated here may be considered as one component of a timing mechanism which acts to perpetuate synaptic signals and thereby maintain an appropriate period of nocturnal pineal function.

Animals↗
PubMed1991

Reinnervation of denervated skeletal muscle by central neurons regenerating via ventral roots implanted into the spinal cord.

The reinnervation of denervated skeletal muscle by central axons regenerating via a ventral root implanted into the spinal cord was examined in rats. The 8th thoracic ventral root was severed and its distal end implanted into the ventro-lateral column of the spinal cord via a stab incision. In control animals the root was severed, but was not implanted into the stab incision. After 12-14 months the animals were examined electrophysiologically to determine the presence or absence of motor units in the 8th intercostal muscle which were reinnervated by centrally derived axons regenerating via the implant. Such units were found in implanted animals, but in none of the controls. Evidence that the motor units were reinnervated by central axons included the facts that the units could be activated either, (1) reflexly (i.e. trans-synaptically) by electrical stimulation of the dorsal roots or spinal cord, or (2) pharmacologically by either the intraspinal injection of glutamate or acetycholine, or by the systemic administration of strychnine. Great care was taken to ensure that the only feasible connection between the spinal cord and the 8th intercostal muscle was via the site of implantation. The EMG signals from the motor units were of large amplitude, typical of reinnervated muscle, and their individual activation resulted in discernible contractions of regions of the T8 intercostal muscle. We conclude that regenerating CNS neurons can be guided to innervate denervated skeletal muscle by the implantation of severed ventral roots into the spinal cord. The neuromuscular synapses formed are functional and persistent. The findings may be relevant to the restoration of function after nervous injuries, such as the avulsion of ventral roots.

Animals↗
PubMed1977

Trans-synaptic induction of adrenomedullary tyrosine hydroxylase activity by choline: evidence that choline administration can increase cholinergic transmission.

Twenty-four hours after rats receive choline chloride (20 mmol/kg, by stomach tube) the activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] increases by 31% within adrenomedullary chromaffin cells. This treatment also causes major elevations in the levels of choline and acetylcholine within the adrenal gland; however, acetylcholine levels return to normal by 16 hr after the choline is given. The daily administration of 10 or 20 mmol/kg of choline for 4 days elevates adrenal tyrosine hydroxylase activity by 29% or 51%, respectively. Such increases in tyrosine hydroxylase activity are not observed in animals given ammonium chloride, another basic chloride-containing compound, by stomach tube or in animals treated with cycloheximide, an inhibitor of adrenal protein synthesis. They are also absent in denervated adrenals. These observations demonstrate that the increase in presynaptic acetylcholine levels produced by giving animals the neurotransmitter's precursor (choline) can be associated with parallel changes in the transmission of signals across cholinergic synapses, probably because more of the transmitter is released per nerve impulse.

Adrenal Medulla↗
PubMedDate not supplied

Conductance and dye permeability of a rectifying electrical synapse.

Electrical synapses provide a basis for efficient signal transmission in a wide variety of nervous systems. These synapses are composed of specialized cell-to-cell contacts known as nexuses or gap junctions which mediate the direct transfer of ions and small molecules between adjacent cell interiors by way of intercellular channels embedded in the junctional membrane. The crayfish giant motor synapse (GMS) was the first cell-to-cell junction clearly demonstrated to operate by an electrical mechanism. Current applied to the presynaptic lateral giant (LG) axon or to the neurite of the postsynaptic giant flexor motoneurone (MoG) spreads passively through the synapse into the adjacent neurone. Each GMS behaves like an electrical rectifier: its conductance is high when LG is positive with respect to MoG, and decreases dramatically when the sign of the trans-synaptic voltage is reversed. We have now examined GMS conductance and dye permeability at thoracic and abdominal levels of the crayfish nerve cord. At both levels, values of GMS chord conductance fit a simple Boltzmann model in which the conductance of individual synaptic channels is assumed to be voltage dependent. Moreover, thoracic synapses display higher limiting conductances than do those at an abdominal level, apparently as a result of their larger size. We also find that synapses at both locations are permeable to the fluorescent dye Lucifer yellow, even in conditions where electrical conductance is low. These results provide a framework for understanding the operation and functional limits of rectifying electrical synapses, and illustrate that dye permeability can be associated even with their relatively low conductance condition.

Animals↗
PubMed1993

Cold-induced increases in phenylethanolamine N-methyltransferase (PNMT) mRNA are mediated by non-cholinergic mechanisms in the rat adrenal gland.

Previously, we reported that cold stress induces a rapid increase in adrenomedullary PNMT mRNA levels, followed by concomitant increases in PNMT immunoreactivity (10). In the present study, the extracellular signals mediating this adaptive response to stress were investigated using northern analysis and RNA slot-blot hybridization. Although adrenal denervation significantly diminished cold-induced increments in adrenomedullary PNMT mRNA levels, it did not completely abolish the cold stress response. In contrast to these results, splanchnectomy completely inhibited cold-induced increments in TH mRNAs in the same tissue samples. These findings indicate that the effects of cold exposure on PNMT mRNA levels are mediated by both neural and non-neural mechanisms, and that adrenal PNMT and TH are differentially regulated in response to cold stress. Surprisingly, the neural component of the PNMT stress response could not be attenuated by peripheral administration of chlorisondamine, a powerful nicotinic ganglionic blocking agent. In contrast, chlorisondamine was effective in inhibiting sympathetic neural activity, as judged by the drug's ability to completely block increases in blood pressure, heart rate, and plasma catecholamines resulting from spinal cord stimulation in pithed rats. The administration of atropine, a muscarinic receptor antagonist, also failed to inhibit cold-induced alterations in adrenal PNMT mRNA. These results suggest that the trans-synaptic induction of adrenal PNMT mRNA involves a non-cholinergic component, and that cold-induced increases in PNMT mRNA are not coupled to acetylcholine-mediated adrenal catecholamine release.

Adrenal Glands↗