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PubMed2005

Neuromodulation.

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Autonomic Fibers, Preganglionic↗
PubMed2007

Predicting implantation with a neuromodulator using two different test stimulation techniques: A prospective randomized study in urge incontinent women.

AIMS: The purpose of this study was to determine whether a percutaneous needle electrode (PNE) technique or a surgical first stage lead placement (FSLP) better predicted whether a patient would progress to implantation of a pulse generator (IPG) in older urge incontinent women. METHODS: Thirty subjects > or =55 years with refractory urge incontinence who had been selected to undergo a test stimulation procedure were randomized to either PNE or FSLP. Thirteen underwent PNE placement and seventeen underwent FSLP placement. If during the test stimulation period subjects had greater than 50% improvement in their incontinence parameters they qualified for permanent lead and/or IPG implantation of the Interstim device. RESULTS: Twenty-one subjects (70%) responded to the test stimulation and underwent implantation, 15/17 (88%) in the FSLP group and 6/13 (46%) in the PNE group. Subjects who were randomized to the FSLP group were significantly more likely to proceed to implantation of the IPG (P = 0.02) than those in the PNE group. There was no significant difference in demographics, pre-test stimulation incontinence parameters or post-stimulation visual analog pain scores between the randomized groups or between test stimulation responders and non-responders. When comparing FSLP and PNE responders, there was no significant difference in the percent improvement in 24-hr pad weight, daily pad usage, or daily incontinence. CONCLUSION: FSLP better predicted progression to implantation of the IPG than a test stimulation with a PNE in an older urge incontinent cohort.

Aged↗
PubMed2001

Pigment-dispersing factor in the locust abdominal ganglia may have roles as circulating neurohormone and central neuromodulator.

Pigment-dispersing factor (PDF) is a neuropeptide that has been indicated as a likely output signal from the circadian clock neurons in the brain of Drosophila. In addition to these brain neurons, there are PDF-immunoreactive (PDFI) neurons in the abdominal ganglia of Drosophila and other insects; the function of these neurons is not known. We have analyzed PDFI neurons in the abdominal ganglia of the locust Locusta migratoria. These PDFI neurons can first be detected at about 45% embryonic development and have an adult appearance at about 80%. In each of the abdominal ganglia (A3-A7) there is one pair of lateral PDFI neurons and in each of the A5-A7 ganglia there is additionally a pair of median neurons. The lateral neurons supply varicose branches to neurohemal areas of the lateral heart nerves and perisympathetic organs, whereas the median cells form processes in the terminal abdominal ganglion and supply terminals on the hindgut. Because PDF does not influence hindgut contractility, it is possible that also these median neurons release PDF into the circulation. Release from one or both the PDFI neuron types was confirmed by measurements of PDF-immunoreactivity in hemolymph by enzyme immunoassay. PDF applied to the terminal abdominal ganglion triggers firing of action potentials in motoneurons with axons in the genital nerves of males and the 8th ventral nerve of females. Because this action is blocked in calcium-free saline, it is likely that PDF acts via interneurons. Thus, PDF seems to have a modulatory role in central neuronal circuits of the terminal abdominal ganglion that control muscles of genital organs.

Abdomen↗
PubMed1984

Central nervous sensitization and dishabituation of reflex action in an insect by the neuromodulator octopamine.

Habituation of excitatory synaptic inputs onto identified motor neurons of the locust metathoracic ganglion, driven electrically and by natural stimuli, was examined using intracellular recording. Rapid progressive reduction in amplitude of EPSPs from a variety of inputs onto fast-type motor neurons occurred. The habituated EPSPs were quickly dishabituated by iontophoretic release of octopamine from a microelectrode into the neuropilar region of presumed synaptic action. The zone within which release was effective for a given neuron was narrowly-defined. With larger amounts of octopamine applied at a sensitive site the EPSP became larger than normal, and in many instances action potentials were initiated by the sensitized response. Very small EPSPs onto a motor neuron, which were associated with proprioceptive feedback, and which were originally too small to be detected above the noise, were potentiated to a level of several mV by the iontophoresed octopamine. A DUM neuron (presumed to be octopaminergic) was found, whose direct stimulation was followed by a strong dishabituating and sensitizing action leading to spikes, of inputs to an identified flexor tibiae motor neuron. The action and its time course were closely similar to those evoked by octopamine iontophoresed into the neuropil in the region of synaptic inputs to the motor neuron. It is concluded that DUM (octopaminergic) neurons exert large potentiating actions on central neuronal excitatory synaptic transmission in locusts.

Animals↗
PubMed1997

Inhibition by 2-arachidonoylglycerol, a novel type of possible neuromodulator, of the depolarization-induced increase in intracellular free calcium in neuroblastoma x glioma hybrid NG108-15 cells.

2-Arachidonoylglycerol was found to inhibit the depolarization-induced increase in [Ca2+]i in NG108-15 cells differentiated with prostaglandin E1 and theophylline in a dose-dependent manner. Such an effect appears to be rather specific to polyunsaturated fatty acid-containing monoacylglycerols such as 2-arachidonoylglycerol. Neither 2-palmitoylglycerol nor free arachidonic acid exhibited appreciable inhibitory activity. These observations raise the possibility that 2-arachidonoylglycerol attenuates the increase in [Ca2+]i, thereby modulating several neural functions in this type of cell.

Arachidonic Acids↗
PubMed2000

Neurosteroids: biosynthesis and function of these novel neuromodulators.

Over the past decade, it has become clear that the brain is a steroidogenic organ. The steroids synthesized by the brain and nervous system, given the name neurosteroids, have a wide variety of diverse functions. In general, they mediate their actions, not through classic steroid hormone nuclear receptors, but through ion-gated neurotransmitter receptors. This paper summarizes what is known about the biosynthesis of neurosteroids, the enzymes mediating these reactions, their localization during development and in the adult, and their function and mechanisms of action in the developing and adult central and peripheral nervous systems. The expression of the steroidogenic enzymes is developmentally regulated, with some enzymes being expressed only during development, while others are expressed during development and in the adult. These enzymes are expressed in both neurons and glia, suggesting that these two cell types must work in concert to produce the appropriate active neurosteroid. The functions attributed to specific neurosteroids include modulation of GABA(A) and NMDA function, modulation of sigma receptor function, regulation of myelinization, neuroprotection, and growth of axons and dendrites. Neurosteroids have also been shown to modulate expression of particular subunits of GABA(A) and NMDA receptors, providing additional sites at which these compounds can regulate neural function. The pharmacological properties of specific neurosteroids are described, and potential uses of neurosteroids in specific neuropathologies and during normal aging in humans are also discussed.

Animals↗
PubMed1993

Neuromodulation of calcium current by extracellular ATP in isolated ventricular myocytes.

The effects of extracellular ATP on the L-tpe Ca2+ current (ICa), action potential, and resting and intracellular Ca2+ levels were examined in enzymatically isolated myocytes from the right ventricles of ferrets. Extracellular ATP decreased the peak amplitude of ICa in a time- and concentration-dependent manner. The concentration-response relationship for ATP inhibition of ICa was well described by a conventional Michaelis-Menten relationship with a half maximal inhibitory concentration of 1 microM and a maximal effect of 50%. Extracellular ATP did not change the resting myoplasmic Ca2+ levels; however, it did decrease the Ca2+ transient. The effects of extracellular ATP were mediated independently of adenosine A1 receptors and a pertussis-toxin sensitive G protein. Pharmacological characterization of receptor subtype using ATP analogs was consistent with ATP binding to a P2Y type receptor.

Action Potentials↗
PubMed2002

Gamma Knife surgery, a neuromodulation therapy in epilepsy surgery!

INTRODUCTION: The more classical approach for Epilepsy surgery is the removal of the epileptogenic zone (ZE). We present a critical review of information in favor of a possible non-destructive effect of radiosurgery in epilepsy surgery. MATERIAL: Clinical material of patients with epilepsies related to a lesion in highly functional areas subjected to radiosurgery with relief of the seizures and no functional worsening is available. We applied direct treatment of the EZ with good efficacy in the absence of destructive aspects on the MR and no functional deterioration (e.g. hypothalamic hamartomas). Experimental studies have shown biochemical differential effect of radiosurgery on the striatum, glial cell elimination, stem cell migration toward the target area, sprouting,... Plasticity phenomenon are induced by radiosurgery when using non necrotizing dosemetry. DISCUSSION: There is clinical and experimental evidence of Gamma Knife capability to induce modulation in the neural system. Detailed mechanism of this modulation and dosemetric parameters enabling to induce such plasticity with no necrosis are still unknown. Subpial transection turning out actually to be quite disappointing, there is a specific rationale to test radiosurgery capability to treat EZ cortex while preserving the underlying function of this cortex when the functional risk for cortectomy is too high.

Brain Diseases↗
PubMed1992

NE/DA interactions in prefrontal cortex and their possible roles as neuromodulators in schizophrenia.

The monoaminergic innervation of the rat prefrontal cortex arises from well-defined mesencephalic nuclei, with noradrenergic (NE) neurons located in the locus coeruleus, dopaminergic (DA) neurons located in the ventral tegmental area, and serotonergic (5-HT) neurons originating in the raphe nuclei. Specific destruction of the NE bundle was found to induce morphological (i.e., sprouting) as well as metabolic (i.e., changes in rate of DA utilization) modifications of mesocortical DA neurons, suggesting that these two catecholaminergic systems have functional interactions within the prefrontal cortex. This was substantiated by experiments showing that DA afferents modulate the sensitivity of cortical post-synaptic beta-adrenergic receptors and that, reciprocally, NE neurons control the sensitivity of cortical D1 receptors. Behavioural and pharmacological data have further indicated that the stimulation of cortical alpha-1 adrenergic receptors inhibits cortical DA transmission at D1 receptors. Secondly, we have attempted to analyze how such interactions between neuromodulatory systems may be related to the development of mental diseases such as schizophrenia. On the basis of studies in the literature describing the effects produced by the ingestion of hallucinogenic drugs or data collected regarding REM sleep, it is postulated that two modes of brain functioning exist: analogical and cognitive. Each mode is characterized by differences in the relative activities of NE, DA and 5-HT neurons. At birth, during REM sleep, and following the ingestion of hallucinogens, the mode of brain functioning is essentially analogical; in contrast, both analogic and cognitive modes are postulated to coexist in the awake state. Oscillations between these two modes are under the control of monoaminergic systems on which an increase in cortical DA release favours the cognitive processing mode, whereas intermittent activations of NE neurons would switch the brain into the analogical mode of processing. It is proposed that schizophrenic patients with "positive" symptoms suffer from an abnormal preponderance of the analogical mode while awake, whereas "negative" symptoms are due to the excessive presence of the cognitive mode. Although pure biological deficits cannot be excluded, these dysfunctions could be related to the absence of particular environmental variables early in the development of these patients. This condition is probably required to establish normal regulatory control of monoaminergic neuronal activity.

Dopamine↗
PubMed2006

Neuromodulators of LTP and NCAMs in the amygdala and hippocampus in response to stress.

Possibly, at the onset of an emotional event the stress hormones permissively mediate plasticity. Specifically, CORT and NE stress hormones participate in modulation of memory consolidation processes in both the amygdala and the hippocampus. In addition, glucocorticoids and norepinephrin bound to adrenoceptors are also involved in modulating the regulation of NCAM polysialylation both in the amygdala and in the hippocampus. PSA-related synaptic remodeling is mobilized for memory formation in particularly challenging circumstances.

Amygdala↗
PubMed1994

Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism.

Markov kinetic models were used to synthesize a complete description of synaptic transmission, including opening of voltage-dependent channels in the presynaptic terminal, release of neurotransmitter, gating of postsynaptic receptors, and activation of second-messenger systems. These kinetic schemes provide a more general framework for modeling ion channels than the Hodgkin-Huxley formalism, supporting a continuous spectrum of descriptions ranging from the very simple and computationally efficient to the highly complex and biophysically precise. Examples are given of simple kinetic schemes based on fits to experimental data that capture the essential properties of voltage-gated, synaptic and neuromodulatory currents. The Markov formalism allows the dynamics of ionic currents to be considered naturally in the larger context of biochemical signal transduction. This framework can facilitate the integration of a wide range of experimental data and promote consistent theoretical analysis of neural mechanisms from molecular interactions to network computations.

Animals↗
PubMed1993

Investigations into the biochemical basis of neuromodulation by 2-phenylethylamine: effect on microtubule protein.

In order to understand the role of 2-phenylethylamine (PE) on neuronal responses, membrane changes have been studied using ESR probes. We report that the anticipated change in lipid membrane fluidity generally implicated in signal transduction has not been observed when PE is added to synaptosomes. As cytoskeletal architecture of presynaptic terminals appears to be involved in synaptic transmission, we non-specifically labeled synaptosomal membrane proteins with the sulfhydryl spin probe N-(2,2,6,6-tetramethyl-piperidine-1-oxyl-4-yl) maleimide (4-MAL-TEMPO). The addition of 2-phenylethylamine was found to induce conformational changes, in decreasing the ratio of weakly to strongly immobilized spin label (W/S) to 65% of the control. Of the membrane proteins labeled, 70-90% of the 4-MAL-TEMPO is covalently incorporated into cytoskeletal proteins. In isolated synaptosomes, incorporated with spin-labeled tubulin, the addition of PE reduced the W/S ratio to 51.6% of that obtained for polymerized microtubules. In vitro, PE reduced tau R of polymerized microtubules by 37%. We propose that the PE interaction with tubulin changes microtubule dynamics which may lead to its neuromodulatory action. The state of microtubular assembly can modulate the responsiveness of second messengers in the cell to the effect of stimulatory agents. The nature and physiological significance of PE interaction with tubulin is currently under investigation.

Animals↗