Regulation of rat APJ receptor messenger ribonucleic acid expression in magnocellular neurones of the paraventricular and supraopric nuclei by osmotic stimuli

The novel apelin receptor (APJ receptor, APJR) has a restricted expression in the central nervous system suggestive of an involvement in the regulation of body fluid homeostasis. The endogenous ligand for APJR, apelin, is also highly concentrated in regions that are involved in the control of drinking behaviour. While the physiological roles of APJR and apelin are not fully known, apelin has been shown to stimulate drinking behaviour in rats and to have a regulatory effect on vasopressin release from magnocellular neurones of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. To determine the role of APJR in the regulation of water balance, this study examined the effects of osmotic stimulation on the expression of APJR mRNA in the magnocellular PVN (mPVN) and SON of salt-loaded and water-deprived rats. Intake of 2% NaCl and water deprivation for 48 h induced expression of APJR mRNA in the mPVN and SON. Using dual-label in situ hybridization histochemistry, we also investigated whether APJR is colocalized within vasopressin neurones in control, salt-loaded and water-deprived rats. APJR mRNA was found to colocalize with a small population of vasopressin-containing magnocellular neurones in control and water-deprived rats. Salt-loading resulted in an increased colocalization of APJR and vasopressin mRNAs in the SON. These data verify a role for APJ receptors in body fluid regulation and suggest a role for apelin in the regulation of vasopressin-containing neurones via a local autocrine/paracrine action of the peptide.     

Axon collaterals of supraoptic neurones: Anatomical and electrophysiological evidence for their existence in the lateral hypothalamus

The magnocellular neurones of the supraoptic nucleus which synthesize and secrete vasopressin and oxytocin have been commonly regarded as simple “output” neurones in that they receive an input, generate an action potential and in turn release hormone from their terminals in the posterior pituitary. Three lines of evidence are presented which suggest that rat supraoptic nucleus neurones also have axon collaterals which terminate in the hypothalamus close to the nucleus. Small injections of horseradish peroxidase were made directly into the nucleus in hypothalamic slices, allowing visualization of the axons of supraoptic neurones. Collaterals of these axons could be observed in regions both dorsal and dorsolateral to the supraoptic nucleus. In a separate series of experiments, sections of perfusion-fixed hypothalamus were stained for vasopressin and oxytocin using specific antisera. Peptide-containing collaterals of both types were observed near the supraoptic nucleus, in a region similar to that seen after horseradish peroxidase injections. Finally, electrophysiological studies were carried out on hypothalamic slices containing the supraoptic nucleus. A small concentric bipolar stimulating electrode was placed directly into the nucleus and activity of lateral hypothalamic neurones within 0.1–1 mm of the nucleus was recorded. Of 68 neurones studied, 52 were exicted by supraoptic stimulation via a synaptic pathway that could be blocked by Ca²⁺ -free solutions containing 18mM Mg²⁺.These studies suggest that supraoptic neurones communicate via axon collaterals with other neurones in the lateral hypothalamus, in addition to their previously well characterised functional role in neurosecretion.     

Involvement of peripheral and central catecholamine systems in neural-immune interactions

In this review, we have attempted to delineate the current state of knowledge of the relationships between the immune system and one chemically specific component of the nervous system, the noradrenergic system, both in the brain and the periphery. We have discussed recent work describing the presence of noradrenergic innervation in lymphoid tissues in the major lymphatic organs. Our findings demonstrate clearly that the regions in which lymphocytes (mainly T cells) reside, and through which they recirculate, receive direct sympathetic neural input. The immune system can, therefore, be considered 'hard-wired' to the brain. The evidence for receptors on cells of the immune system capable of receiving signals from the brain is discussed. The significance of this 'hard-wiring' to the function of the immune system is considered, both with regard to the effect of its disruption on immune responses, and to the direct and indirect effects of sympathetic neurotransmitter substances on lymphocytes and their behavior in vitro and in vivo. Finally, our detailed analysis of changes occurring in central noradrenergic pathways as a result of stimulation of the immune system leads to an emerging picture of feedback loops from the immune system to the brain. Such circuits employ endocrine, and probably autonomic, outflow to modulate and regulate immune responses.     

Increased densities of nitric oxide synthase expressing neurons in the temporal cortex and the hypothalamic paraventricular nucleus of polytoxicomanic heroin overdose victims: Possible implications for heroin neurotoxicity

Heroin is one of the most dangerous drugs of abuse, which may exert various neurotoxic actions on the brain (such as gray matter loss, neuronal apoptosis, mitochondrial dysfunction, synaptic defects, depression of adult neurogenensis, as well as development of spongiform leucoencephalopathy). Some of these toxic effects are probably mediated by the gas nitric oxide (NO). We studied by morphometric analysis the numerical density of neurons expressing neuronal nitric oxide synthase (nNOS) in cortical and hypothalamic areas of eight heroin overdose victims and nine matched controls. Heroin addicts showed significantly increased numerical densities of nNOS immunoreactive cells in the right temporal cortex and the left paraventricular nucleus. Remarkably, in heroin abusers, but not in controls, we observed not only immunostained interneurons, but also cortical pyramidal cells. Given that increased cellular expression of nNOS was accompanied by elevated NO generation in brains of heroin addicts, these elevated levels of NO might have contributed to some of the known toxic effects of heroin (for example, reduced adult neurogenesis, mitochondrial pathology or disturbances in synaptic functioning).     

Pain,Racial Discrimination,and Depressive Symptoms among African American Women

African American women with osteoarthritis (OA) are at high risk of experiencing pain. They report more pain than non-Hispanic White women and men of other racial/ethnic groups. This pain can limit independence and diminish their quality of life. Despite the detrimental effects that pain can have on older African American women with OA, there is a dearth of literature examining factors beyond the OA pathology that are associated with pain outcomes within this population. The purpose of this study was to examine the relationships between racial discrimination and depressive symptoms with pain intensity in African American women with OA. The sample comprised of 120 African American women, aged 50-80 years, with OA, from Texas and New Mexico. The women completed survey booklets to answer study questionnaires. We used multiple linear regression to test associations between racial discrimination, depressive symptoms, and pain intensity. We tested whether depressive symptoms mediated the relationship between racial discrimination and pain intensity by using bootstrapping. Results indicated that racial discrimination was significantly associated with pain intensity and that this relationship was mediated by depressive symptoms, even after controlling for body mass index, years of education, and length of time with OA. Both depressive symptoms and racial discrimination may be modifiable. If these modifiable factors are addressed in this population, there may be decreased pain in middle-aged and older African American women.     

Central oxytocin attenuates augmented gastric postprandial motility induced by restraint stress in rats

Restraint stress delays gastric emptying via uncoordinated motility pattern in rats. Central oxytocin has anxiolytic effects and attenuates the hypothalamic-pituitary-adrenal (HPA) axis in response to stress and facilitates stress-induced delayed gastric emptying. However, the role of central oxytocin in regulating gastric motility remains unknown. Postprandial gastric motility was recorded via a strain-gauge transducer, implanted on the antrum in Sprague–Dawley (SD) rats. To investigate whether central and peripheral oxytocin are involved in gastric motility, oxytocin (10 μg) was administered intracerebroventricularly (icv) and intraperitoneally (ip). Central and peripheral oxytocin administration did not affect the postprandial gastric motility under non-stressed conditions. Restraint stress augmented gastric contractions. Central administration of oxytocin, but not peripheral administration, abolished the augmented postprandial gastric contractions induced by restraint stress. Oxytocin facilitates stress-induced delayed gastric emptying via alleviating uncoordinated gastric motility. Oxytocin might be a candidate for the treatment of stress-induced GI motility disorders.     

Expression of Fos immunoreactivity in rat brain during dehydration: effect of duration and timing of water deprivation

Water deprivation induces expression of the immediate early gene c-fos in specific brain regions, most likely as a result of the activation of cells that are responsive to changes in osmolality and/or blood volume. We hypothesized that the magnitude of c-fos expression would be a function of both the duration of water deprivation and the time of day at which the deprivation started. This study was designed to examine the pattern of Fos-like immunoreactivity (FLI) following water deprivation in rats under normal light/dark conditions (nLD) and reverse light/dark conditions (rLD). Rats were deprived of water but not food either for 0, 5, 16, 24 or 48 h. As expected, hematocrit ratio (HCT), osmolality (OSM), plasma renin activity (PRA) and weight loss increased as a function of duration of water deprivation. In non-deprived rats (0 h), very little FLI was observed in most brain regions. The number of cells showing FLI increased with duration of water deprivation in the supraoptic nucleus (SON), paraventricular nucleus (PVN), organum vasculosum laminae terminalis (OVLT), median preoptic nucleus (MnPO) and subfornical organ (SFO) in both nLD and rLD conditions. However, the pattern of FLI differed between nLD and rLD conditions. Compared to corresponding nLD groups after 5 or 24-h water deprivation, rLD groups had significantly more FLI in SON and PVN, and higher PRA and HCT. Also, weight loss and FLI in the MnPO were greater after 5 h, and FLI in the SFO was greater after 24 h under rLD compared to nLD conditions. Our findings indicate that the magnitude of c-fos expression, and change in weight and plasma parameters were a function of both the duration of water deprivation and the time of day at which the deprivation started. This may result from ingestion of food early in the deprivation periods during the rLD tests, thus producing greater change in osmolality and blood volume.     

中国树下丘脑视上核和室旁核内加压素能神经元的形态和神经纤维的分布

用抗加压素（VP）血清和免疫组化技术，观察了中国树下丘脑视上核（SON）和室旁核（PVN）内VP能种经元的形态和神经纤维的分布。VP能胞体的形态，在SON主部多呈梭形，少数呈多角形；在SON交叉后部，多是多角形，少数是梭形；在PVN，以多角形为主，少数为梭形．VP能纤维的分布：在PVN与SON生部之间，特别是与视交叉上区和现柬背内侧区之间，纤维细而直，多平行分布．在PVN后半外侧，可见部分纤维呈内侧-背外侧向分布；在SON交叉后部的背外侧，纤维是朝向正中隆起处汇集的趋势，其中部分纤维呈串珠状；在正中隆起内带，纤维呈西外侧-内侧向和吻-屠向密集分布，有少数大小不等的免疫反应阳性的聚集体；在正中隆起外带，特别在会体门脉毛细血管排周围，有致密的、成群分布的免疫反应阳性点状结构；在漏斗柄和垂体神经部，可见致密的免疫反应阳性纤维和Herring体，在神经部内的窦状毛细血管周围有致富的、大小不等的免疫反应阳性点状结构．     

Neurophysin in the brain and pituitary gland of normal and scrapie-affected sheep--I. Its localization in the hypothalamus and neurohypophysis with particular reference to a new hypothalamic neurosecretory pathway to the median eminence

By use of an immunofluorescence histochemical technique with a cross-species reactive antiserum to porcine neurophysin-II the precise localization of neurophysin in the pituitary gland and the hypothalamic area of the brain of the sheep has been determined. Neurophysin was confined to neurosecretory pathways originating from the supraoptic and paraventricular hypothalamic nuclei. The major pathway terminates in the neurohypophysis but in addition a second neurophysin-containing pathway proceeds in the external infundibular zone of the median eminence-pituitary stalk and is associated with the presence of vasopressin. In sheep affected with the hereditary degenerative disease known as natural scrapie, this supraoptico-paraventriculo-infundibular pathway is preserved and hypertrophied, while the major pathway to the posterior lobe of the pituitary degenerates. The supraoptic and paraventricular nuclei in the sheep comprise at least two distinct but morphologically similar neuronal populations affected differently by the natural scrapie genome, one undergoing dissolution by middle-age and one surviving and becoming hyperactive. This premature ageing is probably associated with a primary biochemical lesion affecting the rate of the axonal flow of neurosecretory vesicles and of their discharge at synaptic terminals. Possible metabolic and circulatory bases for such an anomaly are considered. The presence of neurophysin in the rostral and caudal adenohypophysis supports the view that vasopressin is acting directly as a trophic-hormone releasing factor, possibly for the quick release of adrenocorticotropic hormone and of growth hormone. The relation of neurophysin-rich aggregations in the neurohypophysis to Herring bodies and the turnover of neurosecretory material are discussed.