Traditional Chinese acupuncture has a history of over 2500 years. It is effective in the treatment of many conditions with few side effects. The best known mechanism is via endogenous opiates and their receptors. In addition to opioids, researchers have focused on the role of central monoamimergic systems. Acupuncture therapy is used not only to relieve pain but also to treat various medical conditions in traditional Chinese medicine (TCM). Some experiments have revealed a relationship between acupuncture and the autonomic nervous system (ANS). Besides, electroacupuncture (EA) can modulate the imbalance between innate and acquired immune systems. This review is focusing on the mechanistic studies of acupuncture that my colleagues and I have performed in Taiwan in recent years. We found that EA analgesia was closely related to not only the serotonergic neurons but also the adrenergic neurons in the central nervous system. The electrophysiological recordings suggested the involvement of the cerebral cortex in acupuncture. Local somatothermal stimulation inhibited the motility of sphincter of Oddi and internal anal sphincter through nitrergic neural release of nitric oxide. Mild local heat stress upregulated hepatic gene expression of heat shock protein 70 and protected the liver from subsequent ischemia-reperfusion injury. These studies supplement the knowledge of the mechanism of acupuncture.
Acupuncture Therapy ; methods ; Adrenergic Fibers ; metabolism ; physiology ; Animals ; Cerebral Cortex ; metabolism ; physiology ; Electroacupuncture ; methods ; Humans ; Medicine, Chinese Traditional ; Moxibustion ; methods ; Neurons ; metabolism ; physiology ; Pain Management ; Proteomics ; Serotonin ; metabolism ; Signal Transduction ; physiology ; Taiwan

Mongolian gerbil (Meriones unguiculatus) has been as an model animal for studing the neurologic disease because of the long-term survival in the condition of water-deprived desert condition. In order to accomplish the this research, first of all another divided the laboratory animals 10groups. In this study of the long term water deprived condition investigated catecholamine synthetic enzymes, tyrosine hydroxylase(TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N- methyltransferase(PNMT) in the brain by using immunohistochemical stain. The results obtained in this study were summarized as following. 1. It were observed TH-IR cells in substantia nigra pars compacta, ventral tegmental area and substantia nigra pars reticular of Midbrian. Most of them were presented in pars compacta and ventral tegmental area, but a few in pars reticular. TH-IR cell decreased until the 5th water-deprived day, increased from the 10th water-deprived day to the 15th water-deprived day and redecreased in the 20th water-deprived day 2. In locus ceruleus and rubrospinal tract were observed TH-IR cells and a few DBH-IR cell. Therefore there was composed of dopaminergic neuron and noradrenergic neuron. 3. The quantity of dopamin in serum were decreased until the 4th water-deprived day, increased from the 5th water-deprived day, redecreased on the 15th water-deprived day and reincreased from the 20th water-deprived day.
Adrenergic Neurons ; Animals ; Animals, Laboratory ; Brain ; Dopaminergic Neurons ; Gerbillinae* ; Locus Coeruleus ; Mesencephalon* ; Pons* ; Substantia Nigra ; Tyrosine ; Ventral Tegmental Area

The distributions and morphological characteristics of neurons displaying immunoreactivity to the catecholamine synthetic enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT) were examined in the adjacent sections of the whole brain in the Striped Field Mouse (Apodemus agrarius coreae) The medulla oblongata were divided into 3 parts (rostral medulla oblongata, area postrema portion of medulla oblongata and caudal medulla oblongata) in this study. In the rostral medulla oblongata, adrenergic (TH-, DBH- and PNMT-positive) neurons were found in dorsal motor nucleus of vagus, nucleus tractus solitarius, dorsal strip and medial longitudinal fasciculus. In the ventrolateral medullary tegmentum of rostral medulla oblongata, adrenergic neurons were found between gigantocellular reticular nucleus and paragigantocellular reticular nucleus. In the area postrema portion of medulla oblongata, noradrenergic neurons were found in the nucleus tractus solitarius, and area postrema. And dopaminergic or adrenergic neurons were also found in dorsal motor nucleus of vagus. In the caudal medulla oblongata, noradrenergic neurons were found in the medial part of nucleus tractus solitarius and superior part of the lateral reticular nucleus.
Adrenergic Neurons ; Animals ; Area Postrema ; Brain ; Immunohistochemistry ; Medulla Oblongata* ; Mice ; Murinae* ; Neurons* ; Solitary Nucleus ; Tyrosine 3-Monooxygenase* ; Tyrosine*

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a strong genetic component. Brain-derived neurotrophic factor (BDNF), which participates in the differentiation and survival of dopaminergic and noradrenergic neurons, could play a role in ADHD development. We aimed to explore the relationships between ADHD and BDNF gene polymorphism. METHODS: We conducted a case-control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test on 151 trios, and compared the results of a continuous performance test (CPT) according to the genotype of the three single nucleotide polymorphisms (rs11030101, rs6265, rs16917204) in the BDNF gene. RESULTS: In the case-control analysis, the AA genotype of the BDNF rs11030101 polymorphism was significantly associated with ADHD only in girls (p=0.024, odds ratio=3.00). The T-G-G haplotype was significantly less frequent (p=0.005) and A-G-G was more frequent (p=0.048) in girls with ADHD than in control girls (global p=0.027). A multivariate analysis of variance for commission errors on the CPT showed a significant main effect for the rs11030101 genotype (p=0.026) and an interaction effect of the rs11030101 genotype and gender (p=0.032) in ADHD probands. CONCLUSION: These results provide preliminary evidence for a gender-specific association between BDNF and ADHD in the Korean population.
Adrenergic Neurons ; Brain-Derived Neurotrophic Factor ; Case-Control Studies ; Genotype ; Haplotypes ; Multivariate Analysis ; Polymorphism, Single Nucleotide

PURPOSE: The urinary bladder (UB) is innervated by both sensory and autonomic nerves. Recent studies have shown that sensory neuropeptides induced contractions in the detrusor muscle. Therefore, in a mouse model, we investigated the presence of interactions between the submucosal sensory nerves and the autonomic nerves that regulate the motor function of the detrusor muscle. METHODS: UB samples from male C57BL/6 mice were isolated, cut into strips, and mounted in an organ bath. Dose-response curves to norepinephrine and phenylephrine were studied in UB strips with and without mucosa, and the effects of preincubation with a receptor antagonist and various drugs on relaxation were also studied using tissue bath myography. RESULTS: Phenylephrine-induced relaxation of the UB strips showed concentration-related effects. This relaxation appeared in both mucosa-intact and mucosa-denuded UB strips, and was significantly inhibited by lidocaine, silodosin, and guanethidine (an adrenergic neuronal blocker). Meanwhile, phenylephrine-induced relaxation was inhibited by pretreatment with propranolol and calcitonin gene-related peptide (CGRP)–depletory capsaicin in UB strips with and without mucosa. CONCLUSIONS: The present study suggests that phenylephrine activates the α-1A adrenergic receptor (AR) of the sensory nerve, and then activates capsaicin-sensitive sensory nerves to release an unknown substance that facilitates the release of norepinephrine from adrenergic nerves. Subsequently, norepinephrine stimulates β-ARs in the detrusor muscle in mice, leading to neurogenic relaxation of the UB. Further animal and human studies are required to prove this concept and to validate its clinical usefulness.
Adrenergic Neurons ; Animals ; Autonomic Pathways ; Baths ; Calcitonin Gene-Related Peptide ; Capsaicin ; Guanethidine ; Humans ; Lidocaine ; Male ; Mice ; Mucous Membrane ; Myography ; Neuropeptides ; Norepinephrine ; Phenylephrine ; Propranolol ; Receptors, Adrenergic ; Receptors, Adrenergic, alpha-1 ; Relaxation ; Urinary Bladder*

BACKGROUND: The gonadotropin releasing hormone (GnRH) neurons represent the final output cells of the neural network that controls fertility. Dopamine (DA) has been shown to control gonadotropin release in many species. However, the direct membrane effects of DA and the related receptors on GnRH neurons remain poorly understood. The purpose of this study was to investigate the direct actions of DA on GnRH neurons and the related receptors using brain slice electrophysiology. METHODS: Gramicidin-perforated patch clamp recordings were made from the GnRH neurons to examine the direct membrane effects of DA in GnRH-EGFP mut5 mice. RESULTS: DA induced hyperpolarization of the GnRH neurons, which was maintained in the presence of tetrodotoxin (TTX), a Na+ channel blocker, suggesting a direct, rather than indirect, action of DA on GnRH neurons. DA-induced hyperpolarizing effects were blocked by prazosin, an alpah1-adrenergic antagonist, and mimicked by phenylephrine (PE), an alpha1-adrenergic agonist. CONCLUSIONS: These data indicate that DA exerts a direct inhibitory effect on GnRH neurons via the alpha1- adrenergic receptors. These results support the general concept that dopaminergic afference represents a predominantly inhibitory component of the GnRH neuronal network.
Animals ; Brain ; Dopamine* ; Electrophysiology ; Fertility ; Gonadotropin-Releasing Hormone ; Gonadotropins* ; Membranes ; Mice ; Neurons* ; Phenylephrine ; Prazosin ; Receptors, Adrenergic ; Tetrodotoxin

Selective labeling of small populations of neurons of a given phenotype for conventional neuronal tracing is difficult because tracers can be taken up by all neurons at the injection site, resulting in nonspecific labeling of unrelated pathways. To overcome these problems, genetic approaches have been developed that introduce tracer proteins as transgenes under the control of cell-type-specific promoter elements for visualization of specific neuronal pathways. The aim of this study was to explore the use of tracer gene expression for neuroanatomical tracing to chart the complex interconnections of the central nervous system. Genetic tracing methods allow for expression of tracer molecules using cell-type-specific promoters to facilitate neuronal tracing. In this study, the rat tyrosine hydroxylase (TH) promoter and an adenoviral delivery system were used to express tracers specifically in dopaminergic and noradrenergic neurons. Region-specific expression of the transgenes was then analyzed. Initially, we characterized cell-type-specific expression of GFP or RFP in cultured cell lines. We then injected an adenovirus carrying the tracer transgene into several brain regions using a stereotaxic apparatus. Three days after injection, strong GFP expression was observed in the injected site of the brain. RFP and WGA were expressed in a cell-type-specific manner in the cerebellum, locus coeruleus, and ventral tegmental regions. Our results demonstrate that selective tracing of catecholaminergic neuronal circuits is possible in the rat brain using the TH promoter and adenoviral expression.
Adenoviridae ; Adrenergic Neurons ; Animals ; Brain ; Cells, Cultured ; Central Nervous System ; Cerebellum ; Gene Expression ; Lifting ; Locus Coeruleus ; Neurons ; Phenotype ; Proteins ; Rats ; Transgenes ; Tyrosine 3-Monooxygenase

PURPOSE: The major pelvic ganglia (MPG) provide the majority of the innervations to the lower urinary tract. The pelvic ganglia are unique autonomic ganglia that contain both sympathetic and parasympathetic neurons. It has been known that the low-threshold voltage-gated (T-type) Ca2 channels are only expressed only in the sympathetic neurons, whereas these channels are absent in parasympathetic neurons. In the present study, we examined the effect of fluoxetine, a world-wide used antidepressant, on the voltage-dependent Ca2 and K currents in the adrenergic neurons of the MPG. MATERIALS AND METHODS: The effect of fluoxetine on the voltage-dependent Ca2 and K currents in the adrenergic neurons of the MPG were examined using the whole-cell patch-clamp technique. RESULTS: Fluoxetine inhibited the voltage-activated Ca2 currents in the adrenergic neurons of the MPG. Both high-threshold (HVA) and low- threshold (LVA, T-type) Ca2 currents were inhibited by fluoxetine with an IC50 of 5.3 and 10.8microM, respectively. Fluoxetine also decreased the both the peak amplitude and the plateau of the outward K currents. The inhibition of the peak K currents by fluoxetine was concentration- dependent with an IC50 of 3.2microM. The inhibitions of the Ca2 and K currents were quickly reversible upon washout of the fluoxetine. CONCLUSIONS: These results provide evidence for the direct inhibition of the voltage dependant Ca2 and K currents by fluoxetine and these inhibitory effects could modify the synaptic transmission in adrenergic neurons of the MPG.
Adrenergic Neurons ; Animals ; Calcium Channels ; Calcium* ; Fluoxetine* ; Ganglia* ; Ganglia, Autonomic ; Inhibitory Concentration 50 ; Neurons* ; Patch-Clamp Techniques ; Potassium Channels* ; Potassium* ; Rats* ; Synaptic Transmission ; Urinary Tract

This study aimed to carry out the reconstruction of whole tract of the vagus nerve using new powerful neurotracer which can migrate easily to the neighboring neurons through synapse and identify whether catecholaminergic neurons exist or not in the central vagal pathways. Pesudorabies virus (PRV-Ba) was used as a neurotracer and antibody to the PRV-Ba was used to localize the tracer in neurons immunohistochemically. The PRV-Ba was injected into the cervical portion of the vagus nerve of Sprague-Dawley rats. After 3 to 4 days of survival periods, brain tissues were fixed, sectioned and stained using anti-PRV-Ba and ABC method subsequently. Motor neurons of the vagus nerve were originated exclsively from dorsal motor nucleus of the vagus nerve and nucleus ambiguus in the medulla oblongata which project fiber by way of nucleus tractus solitarius up to the cerebrum including the paraventricular nucleus. Double labelled neurons were found mostly throughout the brainstem. The adrenergic inputs arose from the C1, C2, and C3 cell groups. Noradrenergic inputs originated predominately from A5 cell group, with lesser contributions from A1 and A7 cell groups as well as locus ceruleus. Some weakly stained TH-immunoreac-tive neurons, presumably dopaminergic, were labelled in the paraventicular nucleus. In conclusion, motor neurons projecting to the vagus nerve includes noradrenergic neurons of the brainstem and from a dopaminergic neurons in the paraventicular nucleus.
Adrenergic Neurons ; Animals ; Brain ; Brain Stem ; Cerebrum ; Dopaminergic Neurons ; Herpesvirus 1, Suid ; Locus Coeruleus ; Medulla Oblongata ; Motor Neurons ; Neurons* ; Paraventricular Hypothalamic Nucleus ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus ; Synapses ; Vagus Nerve*

BACKGROUND/AIMS: Colonic peristalsis is mainly regulated via intrinsic neurons in guinea pigs. However, autonomic regulation of colonic motility is poorly understood. We explored a guinea pig model for the study of extrinsic nerve effects on the distal colon. METHODS: Guinea pigs were sacrificed, their distal colons isolated, preserving pelvic nerves (PN) and inferior mesenteric ganglia (IMG), and placed in a tissue bath. Fecal pellet propagation was conducted during PN and IMG stimulation at 10 Hz, 0.5 ms and 5 V. Distal colon was connected to a closed circuit system, and colonic motor responses were measured during PN and IMG stimulation. RESULTS: PN stimulation increased pellet velocity to 24.6 +/- 0.7 mm/sec (n = 20), while IMG stimulation decreased it to 2.0 +/- 0.2 mm/sec (n = 12), compared to controls (13.0 +/- 0.7 mm/sec, P < 0.01). In closed circuit experiments, PN stimulation increased the intraluminal pressure, which was abolished by atropine (10(-6) M) and hexamethonium (10(-4) M). PN stimulation reduced the incidence of non-coordinated contractions induced by NG-nitro-L-arginine methyl ester (L-NAME; 10(-4) M). IMG stimulation attenuated intraluminal pressure increase, which was partially reversed by alpha-2 adrenoceptor antagonist (yohimbine; 10(-6) M). CONCLUSIONS: PN and IMG input determine speed of pellet progression and peristaltic reflex of the guinea pig distal colon. The stimulatory effects of PN involve nicotinic, muscarinic and nitrergic pathways. The inhibitory effects of IMG stimulation involve alpha-2 adrenoceptors.
Animals ; Atropine ; Autonomic Pathways* ; Baths ; Colon* ; Ganglia ; Guinea Pigs* ; Hexamethonium ; Incidence ; Neurons ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Peristalsis* ; Receptors, Adrenergic ; Reflex