脑胆碱能刺激引起的促钠排泄反应和蓝斑ChAT-IR的变化

目的：观察大鼠侧脑室注射胆碱能激动剂氨甲酰胆碱（CBC）后蓝斑胆碱能神经元活性变化及其与促钠排泄反应的关系。方法：选用SD雄性大鼠通过整体实验和免疫组化方法,观察侧脑室给予氨甲酰胆碱（0．5μg）和俄阿托品（30μg）后肾排钠量的变化及蓝斑胆碱乙酰转移酶（CHAT）免疫反应活性的变化。结果：侧脑室给予氨甲酰胆碱后40min,肾排钠量显著增加,蓝斑的CHAT-IR明显增强（P〈0．05）;阿托品预处理后可明显抑制上述反应。结论：蓝斑的胆碱能神经元参与侧脑室注射氨甲酰胆碱引起的促钠排泄反应。     

Elevated Tyrosine Hydroxylase in the Locus Coeruleus of Suicide Victims

Abstract: The amounts of tyrosine hydroxylase protein in locus coeruleus from nine pairs of antidepressant-free suicide victims and age-matched, sudden-death control cases were determined by quantitative blot immunolabeling of cryostat-cut sections from the caudal portion of the nucleus. In each of the nine age-matched pairs, the concentration of tyrosine hydroxylase was greater in the sample from the suicide victim, with values ranging from 108 to 172% of the matched control value (\-x = 136%). By contrast, there were no differences in the concentrations of neuron-specific enolase protein in the same set of samples. Similarly, the number of neuromelanin-containing cells, counted in sections of locus coeruleus adjacent to those taken for blot immunolabeling analyses, did not differ between the two groups. These data indicate that locus coeruleus neurons from suicide victims contain higher than normal concentrations of tyrosine hydroxylase, thus raising the possibility that the expression of tyrosine hydroxylase in locus coeruleus may be relevant in the pathophysiology of suicide.     

Further Characterization of the Long-Term Effect of RU24722 on Tyrosine Hydroxylase in the Rat Locus Coeruleus

Abstract: Recent data have indicated that the long-lasting increase in tyrosine hydroxylase (TH) protein could be differently expressed in the anterior and posterior locus coeruleus (LC) after a single intraperitoneal injection of RU24722, which has been proposed as a potent activator of catecholaminergic systems. In the present study, we have evaluated the dose and time course responses and the effect of a repeated treatment with RU24722 at 3-day intervals on TH protein level in the anterior and posterior rat LC. The results showed that RU24722 induces a long-lasting increase of TH protein level in the anterior and posterior LC that was maximal 3 days following a single injection of 30 mg/kg. The increase in TH protein was maintained at a constant level after repeated administrations of RU24722 at 3-day intervals. Furthermore, we have investigated whether the effect of the drug on TH protein could be modulated via several hormonal systems. The long-term increase of TH steady-state content after RU24722 was still observed 15 days after castration, adrenalectomy, hypophysectomy, and thyroidectomy. The initial steady-state TH protein level was significantly higher in the anterior LC of thyroid- or hypophysectomized and in the posterior LC of hypophysectomized rats. However, this increase was reversed when animals were housed at 28°C.     

Ontogeny of Tyrosine Hydroxylase Concentration in Locus Coeruleus of Newborn Rats: Long-Term Effects of RU24722

The ontogenetic variations of tyrosine hydroxylase (TH) have been studied in locus coeruleus of developing rats. During the first 2 weeks after birth, a large increase in TH content (6.04-23.99 TH units) in the noradrenergic structure was observed, followed by a period of progressive increase of the protein concentration (42 TH units in adult rats). The expression of TH was studied in the same ontogenetic period after treatment by RU24722 (20 mg/kg, i.p.). The long-term increase in TH concentration produced by the drug was found to follow ontogenetic variations. It becomes significant around the middle of the second week after birth and gradually increases until the 24th day of postnatal development, indicating a maturation of the mechanisms involved in the inducing effect.     

Analysis of the Neuronal Background Impulse Activity in the Rat Locus Coeruleus

Using several techniques of statistical analysis, we studied in detail the extracellularly recorded background impulse activity (BA) of neuronal elements of the rat locus coeruleus (LC). Impulse trains generated by most LC neurons were stationary and demonstrated different levels of regularity; a nonstationary type of BA was observed in 17% of the neurons under study. Statistical parameters of the BA generated by LC neurons showed a wide variability. Distributions of the BA interspike intervals (ISI) of most LC neurons were characterized by more or less expressed bimodality or polymodality. Serial correlation analysis of the ISI durations both in stationary and nonstationary spike trains allowed us to differentiate five main types of the dynamics of ISI successions in the BA of LC neurons.     

Monoamine Metabolism in the Locus Coeruleus Measured Concurrently with Behavior During Opiate Withdrawal: An In Vivo Microdialysis Study in Freely Moving Rats

Abstract: Using microdialysis, changes in monoamine metabolism were monitored in the locus coeruleus of freely moving rats during opiate withdrawal concomitantly with behavioral symptoms. Rats were infused with morphine (2 mg/kg/h, s.c.) or saline for 5 days and challenged with naltrexone (100 mg/kg, s.c.) on day 6. Following naltrexone challenge, the classic behavioral symptoms of morphine withdrawal were observed in rats treated with morphine but not in saline-infused rats. In morphine-dependent rats, naltrexone induced a marked increase (280%) in dialysate concentrations of 3,4-dihydroxyphenylacetic acid, an index of the functional activity of the noradrenergic neurons in the locus coeruleus. The local concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were also increased (70%) during morphine withdrawal. Taken together, these results (a) confirm in unanesthetized rats the hypothesis of an activation by opiate withdrawal of noradrenergic neurons in the locus coeruleus and (b) suggest an increase in serotonergic transmission in the same nucleus during morphine withdrawal.     

Slow Oscillations of the Purkinje Cell Firing Rate Induced by Electrical Stimulation of the Locus Coeruleus in Rats

In anesthetized Wistar rats, we studied the effect of electrical stimulation of the locus coeruleus (LC) on the firing rates of Purkinje cells using spectral analysis. The frequency of extracellularly recorded activity of Purkinje cells was measured before and during the 1st, 5th, 6th, and 11th min after cessation of 10-sec-long LC stimulations. Spectral analysis of the Purkinje cell firing rates (imp./bin, the bin duration was 2^-8 sec) for 60- to 120-sec-long intervals was performed using fast Fourier transformation after digital conversion of unitary spikes. Mean power spectra of the Purkinje cell firing rates (derived from 8-sec-long consecutive epochs at a sampling rate of 256 sec^-1) showed an increase in the slow frequency range (0.1-1.0 Hz) after LC stimulation, particularly due to the slowest components (below 0.5 Hz). This effect lasted more than 1 min and usually less than 6 min after cessation of LC stimulation and could be interpreted as the development of slow oscillations in the Purkinje cell firing. Our results suggest that slow oscillations of the firing rate of cerebellar output neurons, induced by LC stimulation, reflect a specific coordination of the cerebellar neuronal activities (important for a central norepinephrine influence) in regulation of different pathological states.     

The placebo effect and the autonomic nervous system: evidence for an intimate relationship

For many subjectively experienced outcomes, such as pain and depression, rather large placebo effects have been reported. However, there is increasing evidence that placebo interventions also affect end-organ functions regulated by the autonomic nervous system (ANS). After discussing three psychological models for autonomic placebo effects, this article provides an anatomical framework of the autonomic system and then critically reviews the relevant placebo studies in the field, thereby focusing on gastrointestinal, cardiovascular and pulmonary functions. The findings indicate that several autonomic organ functions can indeed be altered by verbal suggestions delivered during placebo and nocebo interventions. In addition, three experimental studies provide evidence for organ-specific effects, in agreement with the current knowledge on the central control of the ANS. It is suggested that the placebo effects on autonomic organ functions are best explained by the model of 'implicit affordance', which assumes that placebo effects are dependent on 'lived experience' rather than on the conscious representation of expected outcomes. Nevertheless, more studies will be needed to further elucidate psychological and neurobiological pathways involved in autonomic placebo effects.     

Agonist Binding to α2-Adrenoceptors Is Elevated in the Locus Coeruleus from Victims of Suicide

Abstract: The binding of an agonist, p-[¹²⁵I]iodoclonidine, and an antagonist, [³H]yohimbine, to α₂-adrenoceptors was measured autoradiographically in the locus coeruleus from 10 pairs of antidepressant-free victims of suicide and age-matched controls. Agonist binding to α₂-adrenoceptors was significantly greater in the locus coeruleus from victims of suicide compared with control subjects. In contrast, antagonist binding to α₂-adrenoceptors in the locus coeruleus did not differ significantly between control and suicide subjects. HPLC analysis of norepinephrine in tissue sections of the locus coeruleus did not reveal any differences between control subjects and suicide victims, suggesting that differences in agonist binding are not a result of differences in retention of the endogenous agonist norepinephrine in tissue sections. The increase in agonist binding to α₂-adrenoceptors in the locus coeruleus of victims of suicide links an altered expression of the high-affinity state of autoinhibitory α₂-adrenoceptors with suicide.     

Coordinate Regulation of the Cyclic AMP System with Firing Rate and Expression of Tyrosine Hydroxylase in the Rat Locus Coeruleus: Effects of Chronic Stress and Drug Treatments

Recent studies have demonstrated that chronic stress increases the firing rate and expression of tyrosine hydroxylase (TH) in neurons of the locus coeruleus (LC), the major noradrenergic nucleus in brain. The present study was undertaken to examine the influence of chronic stress and other treatments known to influence the activity of LC neurons on the cyclic AMP (cAMP) second messenger system in these neurons. Chronic (5 days) cold exposure significantly increased levels of TH immunoreactivity in the LC, as previously reported, but not in substantia nigra (SN) or ventral tegmentum (VT), two dopaminergic nuclei studied for comparison. Chronic cold exposure increased levels of cAMP-dependent protein kinase activity in soluble, but not particulate, fractions of the LC, and increased basal and GTP- and forskolin-stimulated adenylate cyclase activity in this brain region. In contrast, levels of the protein kinase and adenylate cyclase in VT, SN, and frontal cortex were not significantly influenced by cold exposure. To study further the relationship between regulation of LC firing rate, TH expression, and the cAMP system in the LC, other treatments known to influence TH were examined. Reserpine treatment, shown previously to increase levels of TH, was found to increase both LC firing rate and levels of soluble cAMP-dependent protein kinase activity in the LC. 6-Hydroxydopamine, shown previously to increase levels of TH and firing rate of LC neurons, also increased soluble levels of protein kinase activity. Other treatments known to either increase (adrenalectomy) or decrease (chronic imipramine) levels of TH in the LC were also found to increase or decrease, respectively, levels of cAMP-dependent protein kinase activity in this brain region.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Angiotensin II on [3H]Noradrenaline Release and Phosphatidylinositol Hydrolysis in the Parietal Cortex and Locus Coeruleus of the Rat

Angiotensin II (ANGII) (3-100 nM) facilitated the potassium-evoked (22.5 mM) release of [3H]-noradrenaline ([3H]NA) from slices of parietal cortex in a concentration-dependent manner, but did not significantly alter the release of [3H]NA evoked in a similar manner from locus coeruleus slices. The facilitatory action of ANGII was blocked by saralasin (0.1-3 microM). Neither nimodipine (10-30 microM) nor phenylmethylsulphonyl fluoride (1 mM) altered either [3H]NA release or the facilitatory action of ANGII in the parietal cortex. Carbachol (0.01-3 mM) and raised potassium (22.5 mM), but not ANGII (3-100 nM), stimulated the production of inositol phosphates in parietal cortex slices. The potassium-evoked increase in inositol phosphate production was unaffected by ANGII (3-100 nM). In the locus coeruleus, ANGII (3-100 nM) did not stimulate inositol phosphate production. The mechanism underlying the ANGII facilitation of [3H]NA release from the parietal cortex does not appear to involve either nimodipine-sensitive calcium channels, or, as far as we have been able to determine, the release of calcium from intracellular stores following the breakdown of phosphoinositides.     

Molecular Mechanisms of Actions of Interleukin-6 on the Brain,with Special Reference to Serotonin and the Hypothalamo-Pituitary-Adrenocortical Axis

Biological activities of the multifunctional cytokine, interleukin-6 (IL-6) include stimulation of B cell proliferation, immunoglobulin production, and initiation of the acute-phase response. IL-6 affects the CNS in that it activates the hypothalamo-pituitary-adrenocortical (HPA) axis and increases brain tryptophan and serotonin metabolism. IL-6 has been proposed as an important mediator of interaction between the neuroendocrine and immune systems. The peripheral and central effects of IL-6 are presumably mediated through its membrane receptor (IL-6R). IL-6, IL-6R and their respective mRNAs have been detected in several brain regions. Although the functions of cytokines overlap considerably, each displays its own characteristic properties. Expression of IL-6 in the brain has been observed in several CNS disorders, some of which have been associated with disorders of serotonin metabolism. It is proposed that interactions between IL-6 and brain serotonin is a complex process which involves corticotropin-releasing factor (CRF) and opioid peptides. It is likely that the molecular mechanisms underlying the actions of IL-6 on the HPA axis and its other brain functions involve the integrated effects of glutamate, Ca²⁺, 3,5-cyclic AMP, protein kinase C, and other metabolic pathways.     

Localization and distribution of catecholaminergic structures in the nervous system of Phocanema decipiens (nematoda)

The nervous system of Phocanema decipiens was examined with both the formaldeyhyde-induced and the glyoxylic acid fluorescence histochemical techniques. Green catecholaminergic structures were observed in 4 cephalic papillary nerves, 2 fibres with varicosities in the nerve ring as well as the ventral nerve cord and a pair of lateral nerves.The papillary nerves, extending from the nerve ring to the lips region, have cell bodies which are located anterior or adjacent to the nerve ring. Cell bodies of the lateral nerves are found within the lateral cord tissue posterior to the nerve ring. Each of these neurons has 3 processes—one joins with the nerve ring, the other merges with the ventral nerve cord and the third ends abruptly within the lateral cord.     

Ultrastructural Correlates of Enhanced Norepinephrine and Neuropeptide Y Cotransmission in the Spontaneously Hypertensive Rat Brain

The spontaneously hypertensive rat (SHR) replicates many clinically relevant features of human essential hypertension and also exhibits behavioral symptoms of attention-deficit/hyperactivity disorder and dementia. The SHR phenotype is highly complex and cannot be explained by a single genetic or physiological mechanism. Nevertheless, numerous studies including our own work have revealed striking differences in central catecholaminergic transmission in SHR such as increased vesicular catecholamine content in the ventral brainstem. Here, we used immunolabeling followed by confocal microscopy and electron microscopy to quantify vesicle sizes and populations across three catecholaminergic brain areas—nucleus tractus solitarius and rostral ventrolateral medulla, both key regions for cardiovascular control, and the locus coeruleus. We also studied colocalization of neuropeptide Y (NPY) in norepinephrine and epinephrine-containing neurons as NPY is a common cotransmitter with central and peripheral catecholamines. We found significantly increased expression and coexpression of NPY in norepinephrine and epinephrine-positive neurons of locus coeruleus in SHR compared with Wistar rats. Ultrastructural analysis revealed immunolabeled vesicles of 150 to 650 nm in diameter (means ranging from 250 to 300 nm), which is much larger than previously reported. In locus coeruleus and rostral ventrolateral medulla, but not in nucleus tractus solitarius, of SHR, noradrenergic and adrenergic vesicles were significantly larger and showed increased NPY colocalization when compared with Wistar rats. Our morphological evidence underpins the hypothesis of hyperactivity of the noradrenergic and adrenergic system and increased norepinephrine and epinephrine and NPY cotransmission in specific brain areas in SHR. It further strengthens the argument for a prohypertensive role of C1 neurons in the rostral ventrolateral medulla as a potential causative factor for essential hypertension.     

Age-related changes in the innervation of the prostate gland

The adult prostate gland grows and develops under hormonal control while its physiological functions are controlled by the autonomic nervous system. The prostate gland receives sympathetic input via the hypogastric nerve and parasympathetic input via the pelvic nerve. In addition, the hypogastric and pelvic nerves also provide sensory inputs to the gland. This review provides a summary of the innervation of the adult prostate gland and describes the changes which occur with age and disease. Growth and development of the prostate gland is age dependent as is the occurrence of both benign prostate disease and prostate cancer. In parallel, the activity and influence of both the sympathetic and parasympathetic nervous system changes with age. The influence of the sympathetic nervous system on benign prostatic hyperplasia is well documented and this review considers the possibility of a link between changes in autonomic innervation and prostate cancer progression.     

Somatodendritic α2-Adrenoceptors in the Locus Coeruleus Are Involved in the In Vivo Modulation of Cortical Noradrenaline Release by the Antidepressant Desipramine

Abstract: The effect of the antidepressant and selective noradrenaline reuptake blocker desipramine (DMI) on noradrenergic transmission was evaluated in vivo by dual-probe microdialysis. DMI (1, 3, and 10 mg/kg, i.p.) dose-dependently increased extracellular levels of noradrenaline (NA) in the locus coeruleus (LC) area. In the cingulate cortex (Cg), DMI (3 and 10 mg/kg, i.p.) also increased NA dialysate, but at the lowest dose (1 mg/kg, i.p.) it decreased NA levels. When the α₂-adrenoceptor antagonist RX821002 (1 µ M ) was perfused in the LC, DMI (1 mg/kg, i.p.) no longer decreased but rather increased NA dialysate in the Cg. In electrophysiological experiments, DMI (1 mg/kg, i.p.) inhibited the firing activity of LC neurons by a mechanism reversed by RX821002. Local DMI (0.01–100 µ M ) into the LC increased concentration-dependently NA levels in the LC and simultaneously decreased NA levels in the Cg. This decrease was abolished by local RX821002 administration into the LC. The results demonstrate in vivo that DMI inhibits NA reuptake at somatodendritic and nerve terminal levels of noradrenergic cells. The increased NA dialysate in the LC inhibits noradrenergic activity, which in part counteracts the effects of DMI on the Cg. The modulation of cortical NA release by activity of DMI at the somatodendritic level is mediated through α₂-adrenoceptors located in the LC.     

Uridine Nucleotide Receptors and Their Ligands: Structural,Physiological, and Pathophysiological Aspects,with Special Emphasis on the Nervous System

This review presents data on metabotropic uridine nucleotide receptor subtypes (P2UR) activated by UTP, sometimes also by UDP and/or ATP. Some chemical details of receptor subtypes and ligand interactions are described. Ligand-activated P2UR subtypes may couple to different second messengers, yet little is known about the nature of the coupling G-proteins. Data evaluating UTP as a physiological ligand include UTP origin, release and metabolism and illuminate especially roles for P2UR in the nervous system. No evidence shows UTP as a synaptic transmitter; sympathetic neurons may, however, carry P2UR allowing UTP-stimulation of norepinephrine release. UTP and derivatives act as therapeutic agents in several diseases involving mutated genes of transepithelial conductance regulators, including cystic fibrosis. This focuses interest to the synthesis of new compounds. Further, therapeutically used pyrimidine and pyrimidine analogues are suspected to have CNS-pathological effects. The presently scarce information in these areas strongly underlines the need for and importance of intense research on the suspected pyrimidine derivative triggered pathology as well as on the role of P2UR receptors in physiology and pathophysiology.     

Localization and neuroanatomy of catecholaminergic neurons in some rotifer species

We studied Dicranophorus sp., Platyias quadricornis (Ehrb.) and Rotaria tardigrada (Ehrb.). These rotifers, systematically distant from each other, show the same pattern of the catecholaminergic (CA-ergic) part of the nervous system. It is formed of a small (23–24), but steady number of neurons characteristic for each species. Three types of CA-ergic neurons are described. The sizes of neurons vary from to two to ten µm. The distribution of the brain neurons is correlated with body shape. Such a type of nervous system is topographically comparable to the concentrated orthogon of the flatworms.