Histamine in brain development

J. Neurochem. (2012) 122, 872-882. ABSTRACT: The function of histamine in the adult central nervous system has been extensively studied, but data on its actions upon the developing nervous system are still scarce. Herein, we review the available information regarding the possible role for histamine in brain development. Some relevant findings are the existence of a transient histaminergic neuronal system during brain development, which includes serotonergic neurons in the midbrain and the rhombencephalon that coexpress histamine; the high levels of histamine found in several areas of the embryo nervous system at the neurogenic stage; the presence of histaminergic fibers and the expression of histamine receptors in various areas of the developing brain; and the neurogenic and proliferative effects on neural stem cells following histamine H(1) - and H(2) -receptor activation, respectively. Altogether, the reviewed information supports a significant role for histamine in brain development and the need for further research in this field.     

Catecholamine concentration in several structures of the cat and rabbit sympathetic nervous systems during postnatal ontogenesis]

Studies have been made on the content of adrenalin and noradrenalin in the nervous fibers and ganglia of the sympathetic nervous system of cats and rabbits during a postnatal life. In all the structures investigated, high catecholamine content was found within the first month of life on the animals. On further development, total catecholamine content decreases. Age changes in catecholamine content of preganglionic sympathetic fibers and different sympathetic ganglia indicate an effective adrenergic regulation in early postnatal ontogenesis of cats and rabbits.     

Antibodies to synaptic vesicles purified from Narcine electric organ bind a subclass of mammalian nerve terminals

Antibodies were raised in rabbits to synaptic vesicles purified to homogeneity from the electric organ of Narcine brasiliensis, a marine electric ray. These antibodies were shown by indirect immunofluorescence techniques to bind a wide variety of nerve terminals in the mammalian nervous system, both peripheral and central. The shared antigenic determinants are found in cholinergic terminals, including the neuromuscular junction, sympathetic ganglionic and parasympathetic postganglionic terminals, and in those synaptic areas of the hippocampus and cerebellum that stain with acetylcholinesterase. They are also found in some noncholinergic regions, including adrenergic sympathetic postganglionic terminals, the peptidergic terminals in the posterior pituitary, and adrenal chromaffin cells. They are, however, not found in many noncholinergic synapse-rich regions. Such regions include the molecular layer of the cerebellum and those laminae of the dentate gyrus that receive hippocampal associational and commissural input. We conclude that one or more of the relatively small number of antigenic determinants in pure electric fish synaptic vesicles have been conserved during evolution, and are found in some but not all nerve terminals of the mammalian nervous system. The pattern of antibody binding in the central nervous system suggests unexpected biochemical similarities between nerve terminals heretofore regarded as unrelated.     

Peptidergic inputs to sympathetic preganglionic neurons

This paper presents data showing that the sympathetic autonomic areas of the cat thoracolumbar spinal cord contain nerve terminals and fibres with immunoreactivity for at least seven neuropeptides. The distribution in the intermediolateral cell column of the terminals and fibres which contain enkephalin-, neuropeptide Y-, neurotensin-, substance P-, and neurophysin II-like immunoreactivity (ENK, NPY, NT, SP, and NP2, respectively) suggests that these peptides are involved in more generalized functions of the autonomic nervous system. On the other hand, peaks in density of immunoreactivity at certain levels suggest that different levels of influence of sympathetic preganglionic neurons by the various peptides may occur along the length of the thoracolumbar cord. The distribution of terminals and fibres containing somatostatin- and oxytocin-like immunoreactivity (SS and OXY) suggests that these peptides may be part of specific pathways to particular sympathetic preganglionic neurons. The possible sources of the terminals and fibres containing ENK, NPY, NT, SS, and SP include the spinal cord and supraspinal areas, whereas the source of these structures with OXY and NP2 is most likely supraspinal. The data suggest that coexistence of peptides and interactions between structures containing different neuropeptides occur in the spinal autonomic areas. It is speculated that neuropeptides have an important role to play in the regulation of the cardiovascular division of the autonomic nervous system.     

Involvement of the autonomic nervous system in the in vivo TRH-induced increases in the plasma levels of glucagon, insulin and glucose in rabbits

Thyrotropin-releasing hormone, TRH, increases the plasma levels of glucagon, insulin, glucose and free fatty acids in rabbits. However, TRH has no direct effects on the release of hormones neither from the endocrine pancreas in humans nor from the isolated perfused rat pancreas. The aim of the present study was to investigate if the effects of TRH in rabbits were mediated by the autonomic nervous system. The TRH "Roche"-induced hyperglucagonemia was inhibited by phentolamine (an alpha-receptor blocking drug), yohimbine (an alpha-2 -receptor blocking drug) and atropine. The TRH "Roche"-induced hyperinsulinemia was inhibited by propranolol (a beta-receptor blocking drug). The TRH "Roche"-induced hyperglycemia was inhibited by all four drugs. The TRH "Roche"-induced increases in the plasma levels of free fatty acids were not inhibited by the sympathetic and parasympathetic blocking drugs. The effects of TRH "Roche" on the plasma levels of glucagon, insulin and glucose cannot be explained by increases in the plasma levels of catecholamines. TRH, given intravenously into rabbits, may possibly act on regions in the central nervous system which control carbohydrate metabolism and the release of glucagon and insulin from the endocrine pancreas by sympathetic and parasympathetic mechanisms.     

Distribution of the 75-kD Low-Affinity Nerve Growth Factor Receptor in the Primate Peripheral Nervous System

Disruption of the 75-kD low-affinity nerve growth factor (NGF) receptor (p75) has been shown to result in sensory and sympathetic nervous system deficits (Lee et al., 1992a,b). In order to establish precisely which subsets of neurons are capable of responding to neurotrophins (NTs) through the low-affinity NGF receptor, p75 was localized in the primate autonomic and somatic sensory nervous systems. In the autonomic system, cell bodies of some parasympathetic and enteric neurons expressed detectable levels of p75, whereas all sympathetic neurons expressed the protein. In the sensory system, some, but not all, cell bodies were labeled in cranial and spinal sensory ganglia and in the mesencephalic nucleus. Some peripheral and central projections of the sensory neurons were also labeled. Centrally, most of the labeled processes were found in regions containing primarily small unmyelinated fibers, including lamina II of Rexed and areas of the solitary tract and nucleus. Peripherally, labeled processes were associated with unmyelinated nerves and specialized structures such as taste buds and Meissner corpuscles, but not with myelinated processes. This study indicates that the subset of neurons in the autonomic nervous system likely to be capable of responding to neurotrophins is broader than generally thought, and that p75-ex-pressing neurons tend to be clustered. Moreover, in the sensory nervous system p75 is expressed by most cell bodies, but expression in their projections is restricted both peripherally and centrally to unmyelinated processes and nerve terminals.     

Effects of hypothalamic microinjection of PGE2 on body temperature and sympathetic nervous activities in the rabbit

The febrile response and sympathetic nervous response to hypothalamic microinjections of prostaglandin E₂ (PGE₂) were investigated in anesthetized rabbits. Microninjection of PGE₂ (500–1000 ng) caused an increase in rectal temperature of more than 0.3°C in 13 of 50 loci in the preoptic and anterior hypothalamic area (PO/AH). At 8 of these 13 loci, PGE₂ elicited response patterns in the sympathetic nervous system, such as an increase in cutaneous sympathetic nervous activity and decrease in renal sympathetic nervous activity. This pattern of sympathetic nervous responses was induced with a simultaneous increase in rectal temperature of more than 0.5°C. The 8 loci were distributed in the preoptic area, especially in the vicinity of the supraoptic nucleus. Electrolytic lesions of this region were made bilaterally, and intracerebroventricular injection of PGE₂ (8 µg/kg) was found to inhibit fever and sympathetic activity. The results demonstrate that the action of PGE₂ is responsible for the response patterns of sympathetic twigs during fever. The preoptic area, especially in the vicinity of the supraoptic nucleus, is most sensitive to PGE₂ for the patternized response of sympathetic neurons and fever.     

Excessive sympathetic nervous system activity decreases myocardial contractility

The objective of this study was to determine whether myocardial contractility is depressed by intense activation of the sympathetic nervous system. A massive sympathetic discharge was produced by injecting veratrine or sodium citrate into the cisterna magna of anesthetized rabbits (n = 10). Two and one-half hr later, the hearts were isolated and their left ventricular (LV) performance evaluated and compared with the LV performance of hearts isolated from control animals (n = 10). LV performance was evaluated from steady-state peak isovolumic systolic and end-diastolic pressures that were generated at various end-diastolic volumes (LV function curves). The relationship between peak LV systolic pressure (or the average peak developed LV wall stress) and LV end-diastolic volume was rotated downward (P less than 0.01) in the hearts removed from rabbits treated with veratrine or citrate. The LV end-diastolic pressure or LV end-diastolic wall stress of these hearts was not different from control at any end-diastolic volume. The diminished ability of the experimental hearts to develop systolic pressure or wall stress suggests that intense sympathetic activation depressed contractility. Severely damaged myofibers, located largely in the subendocardium, were found in these hearts. Furthermore, the depressed contractility was not related to pulmonary edema since only 2 of 10 rabbits developed edema.     

Ingestion of coffee polyphenols suppresses deterioration of skin barrier function after barrier disruption,concomitant with the modulation of autonomic nervous system activity in healthy subjects

The aim of this study was to evaluate the effect of consumption of coffee polyphenols (CPPs) on the autonomic nervous system activity and decreased skin barrier function caused by sodium dodecyl sulfate (SDS) treatment. In this single-blind, placebo-controlled study, ten healthy male subjects consumed either a beverage containing CPPs or a placebo beverage for four weeks. CPPs significantly suppressed the deterioration in skin barrier function and skin moisture content induced by SDS treatment after the third week. Furthermore, in the heart rate variability analysis, CPPs significantly produced an increase in parasympathetic nervous activity, and a decrease in sympathetic nervous activity after the four weeks of beverage consumption. These results suggest that CPPs might influence the regulation of the autonomic nervous system and contribute to the suppressive effect on deterioration of skin barrier function.     

Skin temperature changes in humans induced by local peripheral cooling

Local peripheral cooling (immerson of legs up to the knees into 12°C water) increased heart rate and blood pressure by 10–20% within the first 3–10 min of cooling. During further cooling heart rate remained elevated, while systolic and diastolic blood pressures decreased to the control value. Data on heart rate indicate a permanent activation of the sympathetic nervous system during local cooling.Skin temperatures (measured topically by thermosensors) decreased on some non-cooled areas of the body (fingers, palms and thighs) immediately after the start of local cooling. On the other hand, skin temperatures on chest and forehead were not influenced. During cooling skin temperatures on thighs remained low, but skin temperatures on fingers tended to increase. Changes in skin temperatures on non-cooled areas of the body indicate that a permanent and generalized activation of the sympathetic nervous system occurs during local cooling.Cold induced cycles of vasodilation (CIVD) were observed on fingers, palms and forearms during local cooling. Minute cycles in skin temperatures were observed on forehead, thighs and chest. Minute cycles coincided with those in the heart rate, indicating a permanent, generalized but discontinuous control of vasomotion by the sympathetic nervous system during local cooling.Infrared thermographic recordings from different body areas indicated that local peripheral cooling lowered skin temperatures in all areas of the body within 5 min. Distant areas of the body (extremities) and pectoral muscles showed greater hypothermia than abdominal areas and head. After 10 min of cooling average skin temperatures in all areas of the body returned to the original level and further fluctuated at approximately 10–15 min intervals.Data indicate that during local cooling skin blood flow in all areas of the body surface permanently fluctuates forming a mosaic of dynamic changes in skin temperatures. Since tympanic temperature increases, while skin temperature decreases immediately after the start of the local cooling, it appears that the initial vasoconstrictor response is being controlled independently of the central temperature input.     

Effects of pressure on the skin exerted by clothing on responses of urinary catecholamines and cortisol,heart rate and nocturnal urinary melatonin in humans

The study investigated how the pressure exerted on the skin by clothing worn while working in the daytime affected the urinary excretion of adrenaline, noradrenaline and cortisol, heart rate, and also melatonin secretion at night. Nine young women (experiment I) and seven young women (experiment II) participated. Participants wore either a 100% cotton jacket (tight clothes, TC) or a 100% cotton T-shirt (loose clothes, LC). Loose-fitting, 100% cotton tank tops and panties were worn as underwear in both the TC and the LC groups. The main results can be summarized as follows: (1) urinary excretion of adrenaline, noradrenaline and cortisol was facilitated, and the amounts of urinary excretion were significantly higher when TC were worn. Heart rate was significantly higher in the TC group; (2) nocturnal urinary melatonin excretion was significantly greater in the TC group. These results are discussed in terms of an enhancement of diurnal sympathetic nervous system activity caused by pressure on the skin produced by tight clothing.     

Functional organization of autonomic neural pathways

There is now abundant functional and anatomical evidence that autonomic motor pathways represent a highly organized output of the central nervous system. Simplistic notions of antagonistic all-or-none activation of sympathetic or parasympathetic pathways are clearly wrong. Sympathetic or parasympathetic pathways to specific target tissues generally can be activated tonically or phasically, depending on current physiological requirements. For example, at rest, many sympathetic pathways are tonically active, such as those limiting blood flow to the skin, inhibiting gastrointestinal tract motility and secretion, or allowing continence in the urinary bladder. Phasic parasympathetic activity can be seen in lacrimation, salivation or urination. Activity in autonomic motor pathways can be modulated by diverse sensory inputs, including the visual, auditory and vestibular systems, in addition to various functional populations of visceral afferents. Identifying the central pathways responsible for coordinated autonomic activity has made considerable progress, but much more needs to be done.     

Adenovirus-mediated gene transfer into the brain stem to examine cardiovascular function: role of nitric oxide and Rho-kinase

The central nervous system plays an important role in the regulation of blood pressure via the sympathetic nervous system. Abnormal regulation of the sympathetic nerve activity is involved in the pathophysiology of hypertension. In particular, the brain stem, including the nucleus tractus solitarii (NTS) and the rostral ventrolateral medulla (RVLM), is a key site that controls and maintains blood pressure via the sympathetic nervous system. Nitric oxide (NO) is a unique molecule that influences sympathetic nerve activity. Rho-kinase is a downstream effector of the small GTPase, Rho, and is implicated in various cellular functions. We developed a technique to transfer adenovirus vectors encoding endothelial nitric oxide synthase and dominant-negative Rho-kinase into the NTS or the RVLM of rats in vivo. We applied this technique to hypertensive rats to explore the physiological significance of NO and Rho-kinase.     

The alternative stimulatory G protein alpha-subunit XLalphas is a critical regulator of energy and glucose metabolism and sympathetic nerve activity in adult mice

The complex imprinted Gnas locus encodes several gene products including G(s)alpha, the ubiquitously expressed G protein alpha-subunit required for receptor-stimulated cAMP generation, and the neuroendocrine-specific G(s)alpha isoform XLalphas. XLalphas is only expressed from the paternal allele, whereas G(s)alpha is biallelically expressed in most tissues. XLalphas knock-out mice (Gnasxl(m+/p-)) have poor suckling and perinatal lethality, implicating XLalphas as critical for postnatal feeding. We have now examined the metabolic phenotype of adult Gnasxl(m+/p-) mice. Gnasxl(m+/p-) mice had reduced fat mass and lipid accumulation in adipose tissue, with increased food intake and metabolic rates. Gene expression profiling was consistent with increased lipid metabolism in adipose tissue. These changes likely result from increased sympathetic nervous system activity rather than adipose cell-autonomous effects, as we found that XLalphas is not normally expressed in adult adipose tissue, and Gnasxl(m+/p-) mice had increased urinary norepinephrine levels but not increased metabolic responsiveness to a beta3-adrenergic agonist. Gnasxl(m+/p-) mice were hypolipidemic and had increased glucose tolerance and insulin sensitivity. The similar metabolic profile observed in some prior paternal Gnas knock-out models results from XLalphas deficiency (or deficiency of the related alternative truncated protein XLN1). XLalphas (or XLN1) is a negative regulator of sympathetic nervous system activity in mice.     

Postnatal development of the scratch reflex in rabbits]

The development of the scratch reflex was studied in newborn (up to 2 months old) rabbits in norm and after elimination or activation of some parts of their nervous system (reticular formation, cerebellum, caudate nucleus, cerebral cortex, superior cervical sympathetic ganglia). The experiments with the section of the brain stem at the border between the medulla and the midbrain showed that in very young (5-10 days old) rabbits in norm the scratch reflex is controlled by the spinal cord with no influences of structures situated above the section's level. Later on the spinal mechanism of the scratch reflex becomes subject to supraspinal influences, among which in 2-3 weeks old animals facilitatory effects are predominant produced, in particular, by the reticular formation and the cerebellum, whereas in older age prevail inhibitory influences of the cerebral cortex, cerebellum, caudate nucleus and the sympathetic nervous system.     

Autonomic nervous system responses as performance indicators among volleyball players

Complex motor skills require planning and programming before execution. The autonomic nervous system (ANS) is thought to transcribe these central operations at the peripheral level: a motor act is thought to be simultaneously programmed by central and autonomic nervous structures. The aim of this study was to verify that autonomic responses reflect the quality of central motor programming leading to successful or failed performance when subjects are required to perform a complex motor skill. The specificity of the ANS response has already been demonstrated through direct recording from sympathetic fibres. It has also been demonstrated through several mental tasks and closed motor skills such as shooting: ANS responses have been shown to be capable of distinguishing success from failure. The aim of this experiment was to test whether ANS responses are capable of distinguishing two levels of achievement during the performance of a skill involving uncertainty (open skill). The subjects had to intercept a ball on a volleyball court, using the forearm receive and pass technique, in order to pass it on to a moving human target. The results were displayed in terms of accuracy: accurate passes were successful and inaccurate passes missed the target. Six autonomic variables were recorded simultaneously during the task: skin resistance and potential, skin blood flow and temperature, instantaneous heart rate and respiratory frequency. Results showed that autonomic variables were capable of distinguishing success from failure in 22 subjects out of 24. This made it possible to build up autonomic patterns characterising subjects' performances, and to confirm that autonomic functioning may reveal information processing in the central nervous system. Thus, the study of autonomic responses may constitute an inferential model of central nervous system functioning. Such a method could be used as an index for the control of mental preparation.     

Gonadosomatic index in Barbus longiceps, Capoeta damascina and their natural hybrid (Pisces, Cyprinidae), versus spermatozoan index in the parental males

The yearly gonadal cycle of two Kinneret teleosts, Barbus longiceps and Capoeta damascina and of their hybrid, was assessed by measuring the gonadosomatic index (GSI) in both sexes, as well as the spermatozoan index (SPI) in the males. SPI was established through a computerized analysis system, using light microscopy images of histological preparations of the testes.
Barbus longiceps specimens had highest GSI in March, 6.31 for males and 1.40 for females. Capoela damascina had highest GS1 in January, 6.63 for males and 6.88 for females. In the male-like hybrids, the highest GSI was 5.57 in February, and in female-like hybrids 1.83 in March; no gametes were ever formed in hybrid gonads. The highest SPI appeared in B. longiceps in April, while in C. damascina the highest SPI was found in March. In both species, the highest SPI was attained several weeks after the highest GSI was observed. It is suggested that the peak of the breeding season of both species is actually represented by the highest SPI. In males, the decreasing GSI, which corresponds to the highest SPI, represents the loss of gonad weight, which is due to the elimination of the spermatid residual bodies, prior to spermiation. In the females the decreasing GSI is the result of ovulation, and characterizes the peak of spawning activity.     

Some pathophysiological aspects of vibration-induced white finger

The level of sympathetic nervous activity was assessed by evaluating cardiovascular responses to a cold test in 63 vibration-exposed workers (50 subjects without vibration white finger (VWF) and 13 subjects at stages 1 and 2 of VWF) and in 41 controls. Blood pressure, heart rate, systolic time intervals and the skin temperature of the third finger of the right hand were monitored throughout the cold test period. Basal urinary excretion of free catecholamines and platelet aggregation indices both in vitro and in vivo were also determined in all subjects. Systolic time intervals such as electromechanical systole index (QS2I) and left ventricular ejection time index (LVETI) were found to be shorter in the vibration-exposed workers with and without VWF than in the controls, both at rest and during cold exposure and recovery (p less than 0.001). A significant inverse relationship between urinary free catecholamines and the duration of LVETI was observed under resting conditions (p less than 0.03). The recovery rate of the basal finger skin temperature after local cooling was slower in vibration workers with VWF than in those without VWF (p less than 0.05) and in the controls (p less than 0.001). Platelet aggregation indices were similar in all groups studied. The results suggest that the level of sympathetic nervous activity is higher in vibration-exposed workers than in controls. In subjects with VWF, sympathetic hyperactivity in combination with local factors such as vibration-induced hyperresponsiveness to cold of the digital vessels may be responsible for finger blanching attacks.(ABSTRACT TRUNCATED AT 250 WORDS)     

肾脏和肾神经在应激、钠盐所致高血压中的作用

本工作采用电生理、生化、放免、电镜等方法,探讨了慢性应激和盐致高血压大鼠交感神经系统和肾脏功能的改变。实验在雄性ＳＤ大鼠上进行。结果表明：（１）高盐大鼠肾血浆流量（ＲＰＦ）和尿钠排泄明显增加,而应激大鼠ＲＰＦ显著下降。（２）电镜显示高盐大鼠近曲和远曲小管上皮细胞及线粒体变大,应激则使细胞萎缩、线粒体变小。（３）高盐大鼠肾皮质ＮａＫＡＴＰ酶活性下降,应激可使其恢复。（４）频谱分析显示应激大鼠低频波动（０２～０９Ｈｚ）明显增加。（５）应激导致大鼠肾素活性（ＰＲＡ）及血管紧张素Ⅱ（ＡＮＧⅡ）水平升高,并能使高盐大鼠低ＰＲＡ和ＡＮＧⅡ水平升高。（６）大鼠去除双侧肾神经后,应激无法造成血压升高、ＲＰＦ下降和ＰＲＡ、ＡＮＧⅡ上升。上述结果提示：肾交感神经系统兴奋性增加介导的肾脏机制,可能在应激和／或盐致高血压发病过程中具有重要作用。     

The Effects of Leptin Administration in Non‐obese Human Subjects

Objective: Body fatness is partly under hypothalamic control with effector limbs that include the endocrine system and the autonomic nervous system (ANS). In previous studies of both obese and never‐obese subjects, we have shown that weight increase leads to increased sympathetic and decreased parasympathetic activity, whereas weight decrease leads to decreased sympathetic and increased parasympathetic activity. We now report on the effect of leptin, independent of weight change, on the ANS. Research Methods and Procedures: Normal weight males (ages 20–40 years) were fed a solid food diet, measured carefully to maintain body weight, for 3 weeks, as inpatients at the Rockefeller University General Clinical Research Center. In a single‐blind, 22‐day, placebo/drug/placebo design, six subjects received leptin 0.3 mg/kilogram subcutaneously for 6 days. ANS measures of amount of parasympathetic control and sympathetic control of heart period (interbeat interval) were made by sequential pharmacological blockade with intravenous atropine and esmolol. Norepinephrine, dopamine, and epinephrine levels in 24‐hour urine collections were also measured as well as resting metabolic rate. Results: Sufficient food intake maintained constant body weight in all subjects. There was no evidence that leptin administration led to changes in energy metabolism sufficient to require additional food intake or to alter resting metabolic rate. Likewise, leptin administration did not alter autonomic activity. Parasympathetic control and sympathetic control, as well as the urinary catecholamines, were not significantly affected by leptin administration. Glucose and insulin levels were increased by food intake as expected, but leptin had no affect on these levels before or after food intake. Discussion: ANS responses to changes in energy metabolism found when food intake and body weight are altered were not found in these never‐obese subjects given leptin for 6 days. Although exogenous leptin administration has profound effects on food intake and energy metabolism in animals genetically deprived of leptin, we found it to have no demonstrable effect on energy metabolism in never‐obese humans. The effects of longer periods of administration to obese individuals and to those who have lost weight demand additional investigation.