Allergic airway inflammation induces tachykinin peptides expression in vagal sensory neurons innervating mouse airways

BACKGROUND: Allergic airway inflammation has been shown to induce pro-inflammatory neuropeptides such as tachykinin peptides substance P (SP) and neurokinin A (NKA) together with related peptide like calcitonin gene-related peptide (CGRP) in nodose sensory neurons innervating guinea-pig airways. OBJECTIVE: The present study was designed to examine the effects of allergen sensitization and challenge on the SP/NKA expression in the jugular-nodose ganglion neurons innervating the murine airways. METHODS: Using retrograde neuronal tracing technique in combination with double-labelling immunohistochemistry, the expression of SP/NKA was investigated in a murine model of allergic airway inflammation. RESULTS: Allergic airway inflammation was found to induce the expression of SP/NKA (13.2+/-1.43% vs. 5.8+/-0.37%, P<0.01) in large-diameter (>20 microm) vagal sensory neurons retrograde labelled with Fast blue dye from the main stem bronchi. CONCLUSION: Based on the induction of tachykinins in airway-specific large-sized jugular-nodose ganglia neurons by allergic airway inflammation, the present study suggests that allergen sensitization and challenge may lead to de novo induction of tachykinins in neurons. This may partly contribute to the pathogenesis of airways diseases such as allergic airway inflammation.     

Change in sympathetic activity,cardiovascular functions and plasma hormone concentrations due to cold water immersion in men

The purpose of this study was to determine whether or not repeated short-term cold water immersions can induce a change in the activity of the sympathetic nervous system and, consequently, in cardiovascular functions in healthy young athletes. Changes in some plasma hormone concentrations were also followed. A single cold water immersion (head-out, at 14°C, for 1 h) increased sympathetic nervous system activity, as evidenced by a four-fold increase (P < 0.05) in plasma noradrenaline concentration. Plasma adrenaline and dopamine concentrations were not increased significantly. Plasma renin-angiotensin activity was reduced by half (P < 0.05) during immersion but plasma aldosterone concentration was unchanged. Stimulation of the sympathetic nervous system during immersion did not induce significant changes in heart rate, but induced peripheral vasoconstriction (as judged from a decrease in skin temperature) and a small increase (by 10%) in systolic and diastolic blood pressures. No clear change in reactivity of the sympathetic nervous system was observed due to repeated cold water immersions (three times a week, for 6 weeks). Neither the plasma renin-angiotensin activity, aldosterone concentration nor cardiovascular parameters were significantly influenced by repeated cold water immersions. A lowered diastolic pressure and an increase in peripheral vasoconstriction were observed after cold acclimation, however. Evidently, the repeated cold stimuli were not sufficient to induce significant adaptational changes in sympathetic activity and hormone production.     

颈交感神经干离断对妊高征大鼠胎盘NO含量及NOS基因表达的影响

目的：观察颈交感神经干离断（TCST）对妊高征（PIH）大鼠胎盘一氧化氮（NO）含量及内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)基因表达的影响。方法:妊娠大鼠随机分5组,每组15只。对照组（C）：自妊娠14 d开始皮下注射生理盐水至孕20 d;妊高征1组、2组（H1、H2）：自妊娠14 d开始皮下注射L-NAME分别为125 mg·kg-1·d-1和62.5 mg·kg-1·d-1，至孕20 d；手术组（O）：妊娠第14 d行右TCST，余同B1;假手术组（S）：妊娠第14 d行右颈交感神经干分离，但不离断，余同 H1。孕21 d剖宫取仔。观察孕鼠血压、尿蛋白，胎鼠的大小、体重、畸形率、死亡率，胎盘NO含量、eNOS mRNA、iNOS mRNA表达。结果:（1） 血压、尿蛋白除基础值外H1、H2组各时点值明显高于C组(P<0.01)；H2组明显低于H1组(P<0.01)；O组与C组相比差异无显著(P>0.05)。（2）胎鼠体重、大小 H1、H2组明显低于C组（P<0.01）；H1组明显低于H2组（P<0.05，P<0.01）;O组与C组相比差异无显著(P>0.05)。死亡率、畸形率变化与上述指标相反。（3）胎盘NO含量及eNOS mRNA、iNOS mRNA表达 H1、H2组明显低于C组（P<0.01）；H1组明显低于H2组（P<0.01，P<0.05）;O组明显高于H1组 （P<0.01），且与C组比无显著差异（P>0.05）。结论：TCST可保护孕鼠免受妊高征的影响，可能与其具有改善孕鼠胎盘组织eNOS mRNA、iNOS mRNA表达和NO含量有关。     

Bicuculline-induced circling from the rat superior colliculus is blocked by GABA microinjection into the deep cerebellar nuclei

In a recent electrophysiological experiment, we showed the deep cerebellar nuclei to be a major source of excitatory input to the superior colliculus. Furthermore, target neurons in the colliculus were found, in every case, to receive convergent tonic inhibitory input from the substantia nigra pars reticulata. In the present study, we investigated these effects in the awake rat. We asked whether circling behaviour, induced by unilateral injection of a GABA antagonist into the lateral colliculus, could be suppressed by concurrent cerebellar inactivation. Rats were chronically implanted with bilateral guide cannulae located above the superior colliculus and deep cerebellar nuclei. Bicuculline methiodide (25 pmol) was microinjected unilaterally into intermediate layers of the colliculus at increasing depths until an optimal contralateral circling response was elicited. This behaviour was taken as the baseline response and was the first of three treatments. The second was an identical manipulation of the colliculus with a concurrent 200-nl microinjection of 1 M GABA into the contralateral deep cerebellar nuclei. The third was a repeat of BIC alone into the colliculus or, if rotation had been suppressed by more than 50% on test 2, the treatment was collicular BIC plus deep cerebellar saline. This latter treatment was used as a control for possible non-pharmacological injection effects. The effect of cerebellar GABA at 26 sites (17 within cerebellar nuclei and 9 outside) on BIC-induced rotation at 15 collicular sites was studied in ten animals. Only GABA injections at sites that fell within the cerebellar nuclei significantly reduced turning (P<0.0001). A full behavioural analysis showed that this was a specific suppression of turning, not the result of general motor impairment. These results provide clear behavioural evidence that opposing, convergent influences from the basal ganglia and cerebellum interact in the lateral superior colliculus to control head and body movements. They furthermore suggest that the tonic deep cerebellar excitation of the superior colliculus could be the driving force in the expression of rotation induced by manipulations of the basal ganglia.     

Evidence that non-NMDA receptors are involved in the excitatory pathway from the pedunculopontine region to nigrostriatal dopaminergic neurons

Summary Extracellular single-neuron recordings were obtained from electrophysiologically identified nigrostriatal neurons in chloral hydrate anesthetized rats, in order to test the hypothesis that excitatory amino acid receptors are involved in responses of these neurons to electrical stimulation of the pontine region where the pedunculopontine nucleus (PPN) is located. The effects of iontophoretic application of excitatory amino acids and their antagonists as well as of cholinergic antagonists were tested on the fast orthodromic excitation of nigrostriatal neurons evoked by stimulation of the PPN region. The N-methyl-D-aspartate (NMDA) receptor antagonist D-a-aminoadipic acid as well as the cholinergic receptor antagonists mecamylamine and atropine failed to suppress the synaptic excitation of nigral neurons. The NMDA receptor antagonist DL-2-amino-5-phosphonovalerate exerted a weak depressant action on the synaptic response in a few neurons only. On the contrary, the broad spectrum antagonists of excitatory amino acid receptors kynurenic acid and gamma-Dglutamyl-amino-methyl-sulphonate were found to block simultaneously both the synaptic excitation and the neuronal responses to iontophoretic pulses of glutamate while leaving unaffected the neuronal responses to local application of acetylcholine or carbachol. The competitive antagonist of non-NMDA receptors 6-cyano-2,3-dihy-droxy-7-nitro-quinoxaline suppressed the synaptic excitation at ejection currents which antagonized neuronal responses to quisqualate and kainate. These results suggest that PPN excitatory fibers synapsing onto pars compacta nigrostriatal neurons utilize an excitatory amino acid as a synaptic transmitter acting preferentially on non-NMDA receptors.     

Development of the NADPH-diaphorase-positive neurons in the sympathetic ganglia

Changes in the distribution of NADPH-diaphorase (NADPH-d) were studied in neurons of the superior cervical ganglion (SCG), stellate ganglion (SG) and celiac ganglia (CG) in newborn, 10-, 20-day-old, 1-month-old, 2-month-old and 6-month-old rats, mice and kittens. NADPH-d-positive neurons were revealed in all sympathetic ganglia in kittens but not in rodents from birth onwards. In kittens, the largest population of NADPH-d-positive cells was found in the SG, the smallest in the SCG (<1%) and we observed only a few cells in the CG. The proportion of NADPH-d-positive cells in the SG increased from 3.1±0.15% in newborn kittens to 9.3±0.63% in 20-day-old animals and decreased further from 8.1±0.75% in 30-day-old kittens to 3.4±0.54% in 2-month-old animals. The content of NADPH-d-positive cells in the CG and SCG did not change during development. There were no differences in cross-sectional area between neurons located in different ganglia of animals from the same age group under study. We conclude that the development of NADPH-d-positive neurons in different sympathetic ganglia has its own time dynamics and is completed by the end of the second month of life.     

Electrophysiological properties of sympathetic preganglionic neurons in the cat spinal cord in vitro

Intracellular recordings were obtained from sympathetic preganglionic neurons of the intermedio-lateral nucleus of the adult cat in slices of upper thoracic spinal cord maintained in vitro. The neurons were identified by their antidromic responses to stimulation of various ipsilateral sites. Sites from which antidromic responses could be evoked were the white ramus, the ventral root, the ventral root exit zone, the white matter between the latter and the outer edge of the tip of the ventral horn, the lateral edge of the ventral horn. Resting membrane potential was –61.3±1.6 mV (mean±SEM), input resistance 67.5±3.7 M, time constant 11.5±1.2 ms. The amplitude of the action potential generated by antidromic or direct stimulation was 77.4±2.3 mV. Threshold for direct spikes was 18.2±1.8 mV. The action potential had an average duration of 3.03±0.16 ms. It showed a prominent hump on the falling phase. The action potential had a tetrodotoxin (TTX)-sensitive and a TTX-resistant component. The latter was abolished by cobalt.Tetraethylammonium, cesium and barium prolonged the action potential duration which acquired a plateau-shape. A prolonged after-hyperpolarization (AHP) followed the sympathetic preganglionic neuron spike. Following a single spike, AHP duration and peak amplitude were 2.8±0.3 s and 16.6±0.7 mV, respectively. The AHP was abolished by cesium or barium, but enhanced by tetraethylammonium. An AHP followed the TTX-resistant spike. EPSPs and IPSPs could be generated by focal stimulation. The EPSP triggered spikes when threshold (15.0±2.0 mV) was reached. The slice of the thoracic spinal cord provides a useful experimental preparation for analysis of cellular properties and synaptic mechanisms of the sympathetic preganglionic neuron.     

A role for the basal ganglia in nicotinic modulation of the blink reflex

Summary In humans and rats we found that nicotine transiently modifies the blink reflex. For blinks elicited by stimulation of the supraorbital branch of the trigeminal nerve, nicotine decreased the magnitude of the orbicularis oculi electromyogram (OOemg) and increased the latency of only the long-latency (R2) component. For blinks elicited by electrical stimulation of the cornea, nicotine decreased the magnitude and increased the latency of the single component of OOemg response. Since nicotine modified only one component of the supraorbitally elicited blink reflex, nicotine must act primarily on the central nervous system rather than at the muscle. The effects of nicotine could be caused by direct action on lower brainstem interneurons or indirectly by modulating descending systems impinging on blink interneurons. Since precollicular decerebration eliminated nicotine's effects on the blink reflex, nicotine must act through descending systems. Three lines of evidence suggest that nicotine affects the blink reflex through the basal ganglia by causing dopamine release in the striatum. First, stimulation of the substantia nigra mimicked the effects of nicotine on the blink reflex. Second, haloperidol, a dopamine (D₂) receptor antagonist, blocked the effect of nicotine on the blink reflex. Third, apomorphine, a D₂ receptor agonist, mimicked the effects of nicotine on the blink reflex.     

Immunoreactive somatostatin-28(1-12) is increased in Huntington's disease

Somatostatin-28(1-12) concentrations were measured in Huntington's disease (HD) postmortem tissue using a specific radioimmunoassay. Concentrations of immunoreactive somatostatin-28(1-12) were significantly increased in the caudate and putamen but were unchanged in cortical areas A9 and A17. Since somatostatin-28(1-12) terminates with the amino acids Arg-Glu-OH, we examined whether this dodecapeptide compound might exert a neurotoxic effect. Injections of somatostatin-28(1-12) into rat striatum showed no evidence of histologic damage.