PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Neuromodulation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources
PubMed2002

CXC chemokine receptors in the central nervous system: Role in cerebellar neuromodulation and development.

Chemokines and their receptors are constitutively present in the central nervous system (CNS), expressed in neurons and glial cells. Much evidence suggests that, beyond their involvement in neuroinflammation, these proteins play a role in neurodevelopment and neurophysiological signaling. The goal of this review is to summarize recent information concerning expression, signaling, and function of CXC chemokine receptor in the CNS, with the main focus on the developmental and neuromodulatory actions of chemokines in the cerebellum.

Cerebellum↗
PubMed1998

Regulation of angiotensin II-induced neuromodulation by MARCKS in brain neurons.

Angiotensin II (Ang II) exerts chronic stimulatory actions on tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DbetaH), and the norepinephrine transporter (NET), in part, by influencing the transcription of their genes. These neuromodulatory actions of Ang II involve Ras-Raf-MAP kinase signal transduction pathways (Lu, D., H. Yang, and M.K. Raizada. 1997. J. Cell Biol. 135:1609-1617). In this study, we present evidence to demonstrate participation of another signaling pathway in these neuronal actions of Ang II. It involves activation of protein kinase C (PKC)beta subtype and phosphorylation and redistribution of myristoylated alanine-rich C kinase substrate (MARCKS) in neurites. Ang II caused a dramatic redistribution of MARCKS from neuronal varicosities to neurites. This was accompanied by a time-dependent stimulation of its phosphorylation, that was mediated by the angiotensin type 1 receptor subtype (AT1). Incubation of neurons with PKCbeta subtype specific antisense oligonucleotide (AON) significantly attenuated both redistribution and phosphorylation of MARCKS. Furthermore, depletion of MARCKS by MARCKS-AON treatment of neurons resulted in a significant decrease in Ang II-stimulated accumulation of TH and DbetaH immunoreactivities and [3H]NE uptake activity in synaptosomes. In contrast, mRNA levels of TH, DbetaH, and NET were not influenced by MARKS-AON treatment. MARCKS pep148-165, which contains PKC phosphorylation sites, inhibited Ang II stimulation of MARCKS phosphorylation and reduced the amount of TH, DbetaH, and [3H]NE uptake in neuronal synaptosomes. These observations demonstrate that phosphorylation of MARCKS by PKCbeta and its redistribution from varicosities to neurites is important in Ang II-induced synaptic accumulation of TH, DbetaH, and NE. They suggest that a coordinated stimulation of transcription of TH, DbetaH, and NET, mediated by Ras-Raf-MAP kinase followed by their transport mediated by PKCbeta-MARCKS pathway are key in persistent stimulation of Ang II's neuromodulatory actions.

Amino Acid Sequence↗
PubMed1996

Neurotransmitter and neuromodulator activity in the gustatory zone of the nucleus tractus solitarius.

The rostral nucleus of the solitary tract (rNST) is the first central relay in the gustatory pathway. While previous investigations have provided a wealth of information on the pattern of central terminations of gustatory afferent fibers, the morphology of synaptic connections of rNST neurons and responses of second order neurons to taste stimuli applied to the tongue, little is known regarding the neurophysiological characteristics of synaptic transmission in rNST. We have used an in vitro brain slice preparation of the rNST to study the intrinsic biophysical properties, neuropharmacology and synaptic responses of rNST neurons. These experiments have revealed that rNST neurons respond to the excitatory amino acid neurotransmitter glutamate, as well as the inhibitory amino acid neurotransmitter gamma amino butyric acid (GABA). By use of glutamate receptor agonists and antagonists we have shown that rNST neurons have AMPA/kainate and NMDA ionotropic glutamate receptors, as well as matabotropic glutamate receptors. In addition, rNST neurons respond to both GABAA and GABAB receptor agonists. The nature of the transmission at the synapse between primary afferent fibers and second order neurons in rNST has been examined by electrical stimulation of the solitary tract to elicit post-synaptic potentials (PSP). Three types of monosynaptic PSP result from stimulation of the solitary tract: excitatory post-synaptic potentials, inhibitory post-synaptic potentials, and a complex mixture of excitatory and inhibitory potentials. These new discoveries provide details about synaptic transmission in rNST and thereby clarify the underlying mechanism by which gustatory information is processed.

Afferent Pathways↗
PubMed2001

Neuromodulation and the functional dynamics of piriform cortex.

Acetylcholine and norepinephrine have a number of effects at the cellular level in the piriform cortex. Acetylcholine causes a depolarization of the membrane potential of pyramidal cells and interneurons, and suppresses the action potential frequency accommodation of pyramidal cells. Acetylcholine also has strong effects on synaptic transmission, suppressing both excitatory and inhibitory synaptic transmission. At the same time as it suppresses synaptic transmission, acetylcholine enhances synaptic modification, as demonstrated by experiments showing enhancement of long-term potentiation. Norepinephrine has similar effects. In this review, we discuss some of these different cellular effects and provide functional proposals for these individual effects in the context of the putative associative memory function of this structure.

Action Potentials↗
PubMed1996

Sensory peptides as neuromodulators of wound healing in aged rats.

An intact nociceptor system of primary afferent sensory nerves is important for the initiation of the inflammatory process and successful tissue repair. Dysfunction of this system with age could be a contributing factor for delayed wound healing in the elderly. This study was designed to examine the role of sensory nerves (using capsaicin-pretreated rats) and the effect of aging on the healing of a thermal wound induced on the interscapular region (using a CO2 laser). The healing endpoint was the time when full wound contraction had occurred. The ability of the sensory peptides, substance P (SP) and calcitonin gene-related peptide (CGRP), in modulating wound healing in aged rats was examined by taking into account the modulatory interaction effects between these peptides. A blister model in the rat hind footpad combined with a laser Doppler flowmeter was used initially to establish these vascular interaction effects. The results showed a significant delay in thermal wound healing in both the capsaicin-treated and aged rats. Using the blister model, we demonstrated the ability of SP and CGRP to induce a limited and a prolonged vasodilator response, respectively. When tested together, SP attenuated the vascular effect of CGRP, an effect that was reversed using the tachykinin antagonist spantide II. When injected at the wound site, SP and CGRP were equally potent in promoting wound healing in aged rats. The beneficial effect of taking the interaction effects into account was most evident in a group of rats that received the tachykinin antagonist as part of their initial treatment with CGRP and 6 h later, an injection of SP; the time to complete wound closure was 11.3 +/- 0.6 days compared to 21.0 +/- 0.9 days in aged controls. We contend that would healing in aged rats can be accelerated by exogenous administration of sensory peptides. Furthermore, modulatory interaction effects between sensory peptides should be taken into consideration when designing any treatment protocol that purports to accelerate wound healing.

Aging↗
PubMed1995

Vesicular monoamine uptake by digitonin-permeabilized PC12 cells: inhibitory effect of neuromodulators and drugs on the amine transport.

Vesicular amine transport is crucial for activity of monoaminergic neurons since translocation of cytosolic amine to storage vesicles is required for both exocytotic release and reuptake of the neurotransmitter. We developed a convenient assay system for vesicular amine transport based on permeabilizing the plasma membrane of pheochromocytoma PC12 cells with digitonin at concentrations of 100 to 150 microM. Serotonin (5HT) is a better substrate than either epinephrine or norepinephrine in this assay system. In the presence of 2 mM ATP, 5HT uptake by the permeabilized cells increased linearly for at least 30 min at 25 degrees C, whereas without addition of exogenous ATP, 5HT uptake reached an apparent plateau after 20 min incubation. Reserpine (500 nM) completely blocked the ATP-dependent 5HT uptake in this system whereas nomifensine (10 microM) had no effect, indicating specificity for vesicular transport. Treatment of intact PC12 cells with AMP dose-dependently decreased 5HT uptake with an EC50 of 20-30 microM as measured after cell permeabilization. Treatment of the intact PC12 cells with forskolin and phorbol 12-myristate 13-acetate prior to permeabilization also down-regulated vesicular 5HT transport, whereas the addition of either of these agents into the reaction mixture for the amine uptake by already permeabilized cells did not alter the vesicular uptake activity. Thus, the system can be applied to studies on regulation of the vesicular amine transport by physiological signaling molecules, intracellular messengers, and drugs.

Adenosine Monophosphate↗
PubMed2003

Sonic hedgehog is a neuromodulator in the adult subthalamic nucleus.

It is well established that members of the hedgehog family are involved in tissue patterning during development. We herein show that sonic hedgehog signaling molecules are differentially regulated by dopamine depletion in the basal ganglia of adult animals and specifically that sonic hedgehog levels are reduced in an animal model of Parkinson's disease. In addition, we show that sonic hedgehog protein inhibits electrical activity in the subthalamic nucleus, a key element of basal ganglia, within minutes of application. As the subthalamic nucleus is overactive in parkinsonism, we suggest that enhancement of sonic hedgehog signaling in the subthalamic nucleus may be of therapeutic value in Parkinson's disease.

Animals↗
PubMed2002

Sacral neuromodulation: new applications in the treatment of female pelvic floor dysfunction.

PURPOSE OF REVIEW: The first sacral nerve stimulators implanted by Tanagho and Schmidt (1981) were performed for the indications of urinary urge incontinence, urgency-frequency, and nonobstructive urinary retention. Since that time, observations have been made for benefits beyond voiding disorders. These additional benefits have included re-establishment of pelvic floor muscle awareness, resolution of pelvic floor muscle tension and pain, decrease in vestibulitis and vulvadynia, decrease in bladder pain (interstitial cystitis), and normalization of bowel function. RECENT FINDINGS: Therapy for fecal incontinence in patients with a structurally intact sphincter mechanism appears to be very promising. Investigators agree that there is a role for sacral nerve stimulation in patients with urge fecal incontinence that have failed conservative efforts. Objective manovolumetric testing shows an increase in resting pressure, an increase in voluntary contraction pressure, a decrease in rectal volumes which cause first urge, a decrease in rectal volume to initiate first urge to defecate, and an increase in duration of maximum squeeze pressure. Intractable interstitial cystitis is defined as patients that have failed conventional therapy. Historically, the only option remaining was extirpative surgery or diversion. Maher et al. reported on patients with intractable interstitial cystitis who had undergone sacral nerve stimulation. They found that 73% of these patients had a reduction in pelvic pain, daytime frequency, nocturnal urgency and an increase in average voided volumes. The final area of interest concerns refractory pelvic pain. Siegal et al. reported a decrease in severity, number of hours of pain, and improved quality of life measures in patients who underwent transforamenal sacral nerve stimulations. These patients had all failed conventional pain therapy. SUMMARY: While the data are encouraging in these new arenas of pelvic floor disorders, investigators acknowledge the need for multicenter, statistically powered studies to evaluate the validity of these findings.

Cystitis, Interstitial↗
PubMed2000

Neuromodulation of the prefrontal cortex during sleep: a microdialysis study in rats.

To test the hypothesis that biogenic amines of the prefrontal cortex are involved in state-dependent cortical and behavioural activation, changes in extracellular levels of serotonin (5-HT), dopamine (DA), and noradrenaline (NA) were determined during the sleep-wake cycle in freely moving rats using microdialysis probes with parallel EEG recording. Serotonin gradually increased up to 450% during wakefulness (W) as compared to slow wave sleep (SWS), before decreasing toward stable levels during the next episode of SWS. Dopamine and its metabolite homovanillic acid (HVA) were reduced during W as compared to SWS. Although contradictory with the generally admitted enhancement of DA activity related to vigilance, this may be due to the particular role of DA neurons in the prefrontal cortex. However, DA and HVA showed dramatic changes announcing the transition between SWS and W. During paradoxical sleep (PS), DA and 5-HT showed complex changes, the direction of which depended on whether PS was followed by SWS or W. Biogenic amines of the prefrontal cortex are probably involved in cortical and behavioural activation.

Animals↗
PubMed2001

Changes in response modulation of cat perigeniculate neurons related to EEG state and application of neuromodulators.

Spike activity of single perigeniculate (PGN) neurons was recorded in the anaesthetized (N2O/halothane) and paralysed cat during presentation of moving gratings of optimal spatial frequency. Typically, the ongoing (tonic, spontaneous) activity of PGN cells increased during a rise in EEG delta power accompanied by a reduction and often a total loss of spike rate modulation by the moving grating. The opposite behaviour was found when the EEG delta power vanished. Micro-iontophoretically applied acetylcholine (ACh) had an effect similar to a decrease in EEG delta power, decreasing ongoing activity but increasing the response modulation depth. The opposite effect could be achieved with the excitatory action of serotonin (5-HT), mimicking a strengthened EEG delta power. These data support previous data indicating that PGN neurons contribute to spatio-temporal tuning of subcortical visual activity in a state-dependent way.

Acetylcholine↗
PubMed2001

Posterior tibial nerve stimulation as neuromodulative treatment of lower urinary tract dysfunction.

PURPOSE: Recently, intermittent percutaneous posterior tibial nerve stimulation was introduced as a treatment modality filling the gap between conservative and surgical therapies in patients with certain types of lower urinary tract dysfunction. MATERIALS AND METHODS: In a prospective multicenter trial posterior tibial nerve stimulation was evaluated in 37 patients who presented with symptoms of bladder overactivity, that is the urgency and frequency syndrome and/or urge incontinence, and 12 with nonobstructive urinary retention. Results were recorded in voiding diaries and on quality of life questionnaires before and after treatment. Patients were classified as responders, including those in whom therapy was successful and chose to continue treatment after the initial 12 weeks, and nonresponders, those who chose to stop treatment. RESULTS: Overall, a positive response was seen in 60% of all patients. In patients with bladder overactivity a statistically significant decrease was observed in leakage episodes, number of pads used, voiding frequency and nocturia, and an equal increase in mean and smallest volume voided. Improvements were also seen in nonobstructive urinary retention, including number of catheterizations, total and mean volume catheterized, and total and mean volume voided. Disease specific quality of life and some domains of general quality of life improved, especially of bladder overactivity. Only mild side effects were observed. CONCLUSIONS: Posterior tibial nerve stimulation is a minimally invasive and successful treatment option for patients with certain types of lower urinary tract dysfunction.

Adult↗