损毁弓状核对大鼠骨组织形态计量学的影响

目的： 研究损毁下丘脑弓状核对大鼠骨组织形态计量学的影响。 方法： SD大鼠于出生后第1、3、5、7、9 d皮下注射10％谷氨酸单钠(MSG)（4 g/kg BW），对照组同法注射等体积生理盐水，并设MSG毒性对照组，于70 d龄同法注射MSG，各组大鼠皆存活至160 d。用3％戊巴比妥钠腹腔麻醉，用4％多聚甲醛经左心室行全身灌注，取脑作下丘脑弓状核冠状面切片，HE染色。取右侧胫骨常规脱钙，石蜡包埋，矢状面连续切片，胶原特殊染色，用于显示骨小梁结构。HE染色用于破骨细胞计数。图像分析仪对弓状核正中隆起切面和骨组织进行照片和计量。用放免法测血清中GH（生长素）、E2（雌二醇）和T（睾酮）含量。 结果： MSG大鼠弓状核神经细胞数量显著减少，GH和E2、T水平明显降低，骨量显著减少，发生骨质疏松，NS组和MSG毒性对照组弓状核、GH、E2、T和骨组织无明显改变。 结论： ①MSG大鼠骨组织的改变不是MSG对垂体和骨组织的毒性作用所致；②下丘脑弓状核参与骨代谢的调控；③通过GH和性激素作用是ARC参与骨代谢调控的重要途径。     

生后早期大鼠下丘脑核团发育的形态学变化

目的　了解生后早期大鼠下丘脑核团发育情况 ,为相应行为变化提供解释证据。方法　采用 10、13、16d龄雄性大鼠各 10只 ,制作火棉胶连续切片 ,应用计算机分析系统对下丘脑核团进行观察结果。结果　 13d龄组大鼠下丘脑核团各项体视学数据均大于 10d龄组 ,而与 16d龄组相比左别无显著性 ;13d龄组大鼠细胞密度高于 10d龄组 ,而 16d龄组比 13d龄组增高程度更为明显。结论　生后 13d左右的大鼠下丘脑显著发育阶段与大鼠行为改变有明显的变化     

Leucine-enkephalin-like immunoreactive fibers in the medial preoptic area of the rat: their distribution and origin

Summary We studied the distribution of fibers with leucine-enkephalin — like immunoreactivity (L-ENKI) in the medial preoptic area (MPO) of the rat, and the origins of such fibers, using indirect immunofluorescence and a combination of a retrograde tracer with immunocytochemistry that we have developed. These fibers were very dense throughout the rostro-caudal part of the MPO. The distribution was uneven with the highest density in the lateral part. Destruction of the arcuate nucleus, which contains a group of L-ENKI neurons, resulted in the marked reduction of these fibers in the ipsilateral MPO, suggesting that most of these fibers originate in this nucleus. This was also suggested by the fact that injection of biotin-wheat germ agglutinin into the MPO labelled many neurons in the arcuate nucleus ipsilaterally. Simultaneous staining with antiserum showed that some of these neurons are L-ENKI.     

Dendritic arborization and axon trajectory of neurons in the hypothalamic arcuate nucleus of the rat

Summary Dendritic arborization patterns of neurons in the hypothalamic arcuate nucleus and the course of their axons outside the median eminence were studied using Golgi material, electron microscopic detection of degenerated axon terminals following surgical interference, and horseradish peroxidase technique.Two kinds of neurons can be distinguished in the arcuate nucleus: small fusiform and somewhat larger polygonal cells. Fusiform neurons having two, sparsely arborizing stem dendrites are localized mainly in the medial and dorsal parts of the nucleus. A variant of the fusiform neurons (pear shaped cells) has only one dendritic stem, and the axon originates at the other pole of the neuron. These latter cells are found along the ependymal wall of the third ventricle. Polygonal neurons which occupy the ventral and lateral portions of the nucleus have 4–5 repeatedly branching stem dendrites. In addition to the well known course of the axons of the arcuate neurons towards the median eminence, there are axons of both fusiform and polygonal cells which leave the nucleus in lateral or dorsolateral direction. Axons having this course frequently issue a collateral branch along the first 100–150 m of their trajectory.A knife-cut through the arcuate nucleus or along its lateral border resulted in degeneration of axon terminals in the area between the arcuate and ventromedial nuclei, and in a ventromedial sector of the ventromedial nucleus itself. A cut located in the area between the arcuate and ventromedial nuclei caused degenerated axon terminals over a large part of the ventromedial nucleus with a considerable increase in the ventromedial portion.Labeled fusiform and polygonal neurons can be seen in the arcuate nucleus following the injection of horseradish peroxidase into the lateral hypothalamus.The results suggest unequivocally that the neurons in the arcuate nucleus have efferent connections not only towards the median eminence but also to the hypothalamic ventromedial nucleus and lateral hypothalamic area.     

Estrogen reduces the excitability of the female rat medial amygdala afferents from the medial preoptic area but not those from the lateral septum

Electrical stimulation of the medial amygdala (AMY) elicited antidromic action potentials in neurons in the preoptic area (POA) and the lateral septum (LS) of 36 urethane-anesthetized ovariectomized female rats, which were either treated with estrogen o not treated. The extracellular potentials from the two sites showed similar characteristics, with the exception of the sensitivity to estrogen: they had latencies between 3 and 35 ms. Thresholds were as low as 100 A. The mean relative refractory period was 2.2 ms. The peak-to-peak amplitudes of the positive-negative biphasic potential ranged from 1.0 mV to 12.0 mV. Estrogen had site-specific effects on parameters of antidromic activation in the POA. Estrogen-treated rats had a significantly higher threshold (937 vs 664 A) and a longer refractory period (2.5 vs 2.1 ms) than the ovariectomized rats (P < 0.05 for each). The effects were absent in the LS. Selective cutting of the stria terminalis diminished the AMY-induced antidromic responses in the POA and LS. Electrical stimulation of the stria blocked the AMY-induced antidromic potentials by collision. Thus, estrogen-sensitive POA efferents as well as non-estrogen-sensitive LS efferents project to the AMY via the stria terminalis. Reductions in axonal excitability would inhibit neural conduction and transmission. Estrogen may therefore reduce the AMY inputs from the POA, without affecting those from the LS. Such alterations in the neural impulse flow may underlie estrogen-dependent neuroendocrine or behavioral regulation.     

Projection of scrotal thermal afferents to the preoptic and hypothalamic neurons in rats

Effects of thermal stimulation (18–41.5°C) of the scrotum were observed on neurons in the preoptic area and hypothalamus (POHY) in anesthetized rats. Changes in firing rate of POHY neurons occurred, with three exceptions, within the scrotal temperature range of 30–41°C. There was no dynamic response and little or no sign of rapid adaptation. Out of 46 warm-sensitive neurons, 34 increased and 9 decreased in firing rate with a rise in scrotal temperature. Out of 26 cold-sensitive neurons, 19 were excited and 4 were suppressed by scrotal cooling. The 3 exceptions were excited by scrotal warming above 36°C, and were also excited by cooling below 30°C. Out of 54 thermally-insensitive neurons, 16 were excited by scrotal warming, 7 by cooling and 2 by warming and cooling. The scrotal temperature change needed to produce full change in POHY neuronal activity varied from less than 1°C to 7°C, and was usually less than 4°C. Thermal stimulation of either half of the scrotum had identical influence on the same POHY neuron.     

In vivo GABA release from the medial preoptic area of diestrous and ovariectomized rats

Summary The push-pull cannula technique was used to examine the endogenous release of GABA from the medial preoptic area (MPO) of unanesthetized rats. In diestrous females the mean resting release of GABA was 27.1±2.0 pmol/min. GABA release was significantly elevated by increasing the potassium concentration in the perfusion solution to 50 mM, whereas it was dramatically inhibited by mercaptoproprionic acid (1.0 mM), a glutamic acid decarboxylase inhibitor. A comparison between diestrous females and chronically castrated animals indicated that endogenous GABA release in OVX animals was only 60–70% of that in diestrous animals. A model for the presynaptic inhibition of NE by estrogen receptive GABAergic neurons in the MPO is proposed.Partially supported by the German Research Society (grant No. WU 60/5)Dr. Ondo was supported by a NICHHD Research Career Development Award (HD 00248)     

A quantitative ultrastructural analysis of the distribution of amygdaloid fibres in the preoptic area and the ventromedial hypothalamic nucleus

Summary Section of the stria terminalis in the rat causes electron dense degeneration of 10–20% of the axon terminals in the preoptic area and in the ventromedial hypothalamic nucleus 2 days after operation. The neuropil of these two areas has been examined quantitatively with the electron microscope. In these areas the majority of the non-amygdaloid synapses are upon either the shafts or the spines of dendrites. In both areas there are more synapses upon dendritic shafts than on spines, but in the ventromedial nucleus there are significantly more spine synapses than in the preoptic area. In the preoptic area the stria terminalis fibres are distributed more or less equally on shafts and spines whereas in the ventromedial nucleus they terminate preferentially upon dendritic spines. This evidence that amygdaloid fibres terminate differently in the preoptic area and in the ventromedial hypothalamic nucleus is discussed in relation to functional evidence that both these areas play important but different roles in the control of reproductive functions.To the memory of Sir Wilfrid E. Le Gros Clark     

Assessing the role of the medial preoptic area in ethanol-induced hypothermia

Administration of ethanol produces hypothermia. The preoptic area/anterior hypothalamus (POA/AH) contains warm- and cold-sensitive neurons that are important for temperature regulation. The present study evaluated the effect of ethanol on Fos immunoreactivity (Fos-ir) in the medial preoptic area (MPOA) and the effect of lesions to the MPOA on ethanol-induced hypothermia. Rats receiving 1.5-g/kg ethanol showed an increase in Fos-ir in the MPOA. However, lesions to the MPOA did not affect core body temperature. These findings indicate that ethanol increases neural activity in the MPOA, but this increased activity does not influence ethanol-induced changes in core body temperature.     

Somatostatin-mRNA expression in brainstem projections into the medial preoptic nucleus

The medial preoptic nucleus plays an important role in the regulation of neuroendocrine processes, vegetative functions, sexual behaviour and the modulation of the somatomotoric system. The connections of the medial preoptic nucleus to other areas of the central nervous system are very complex, and the area receives afferents using numerous transmitters and neuropeptides. Previous investigations have shown that this nucleus receives afferents from various brainstem nuclei that also contain somatostatinergic neurons. This study was carried out to investigate if somatostatin-projecting neurons of the brainstem are afferents to the medial preoptic nucleus. This was approached by combining somatostatin-mRNA in situ hybridisation with True Blue retrograde tracing. Our results demonstrate somatostinergic brain-stem projections into the medial preoptic nucleus mainly in the pedunculopontine nucleus and in the nucleus of the solitary tract (50% together). Other important somatostatinergic afferents into the medial preoptic nucleus originate in the cuneiform area, the dorsal parabrachial nucleus and in the lateral reticular nucleus (37% together). Less important are the somatostatinergic projections coming from the central grey, the laterodorsal tegmental nucleus, the locus coeruleus and the nucleus raphe magnus. Considering that these areas are involved in diverse functions such as cardiovascular regulation (nucleus of the solitary tract), transmission of visceral sensibility (dorsal parabrachial nucleus), modulation of the somatomotoric system (pedunculopontine nucleus) and in the regulation of neuroendocrine mechanisms (locus coeruleus), it seems tenable that the somatostatin projections demonstrated here also have a diverse functional quality within the medical preoptic nucleus where they terminate.Abbreviations ac anterior commissure - acp anterior commissure, posterior part - AP area postrema - Arc arcuate hypothalamic nucleus - BL basolateral amygdaloid nucleus - BM basomedial amygdaloid nucleus - CA1 CA1 field of Ammon's horn - cc corpus callosum - CG central grey - Cnf cuneiform area - Cu cuneiform nucleus - CPu caudate putamen - DCo dorsal cochlear nucleus - DM dorsomedial hypothalamic nucleus - DPB dorsal parabrachial nucleus - DR dorsal raphe nucleus - DTg dorsal tegmental nucleus - ec external capsule - En endopiriform nucleus - f fornix - FR/Pn pontine reticular formation - Gr gracile nucleus - hipp hippocampus - La lateral amygdaloid nucleus - LC locus coeruleus - LDTg laterodorsal tegmental nucleus - LHRH luteinizing hormone-releasing hormone - Lo lateral olfactory tract - LPO lateral preoptic area - LRt lateral reticular nucleus - LS lateral septum - MdD dorsal reticular nucleus of medulla oblongata - mlf medial longitudinal fasciculus - mfb medial forebrain bundle - mlPP area from peripeduncular nucleus caudally to adjacent parts of medial lemniscus rostrally - MnPN median preoptic nucleus - MPN medial preoptic nucleus - MPO medial preoptic area - MRG median raphe group - OX optic chiasm - PaPC parvocellular paraventricular hypothalamic nucleus - Pe periventricular hypothalamic nucleus - PPTg pedunculopontine tegmental nucleus - RMg raphe magnus nucleus - RPn raphe pontis nucleus - RtTg reticulotegmental nucleus - SC superior colliculus - SCh suprachiasmatic nucleus - Sol nucleus of the solitary tract - Sp5 nucleus of the spinal tract of the trigeminal nerve - SubC subcoeruleus nucleus - VMH ventromedial hypothalamic nucleus - VTA ventral tegmental area - III third ventricle     

下丘脑弓状核KNDy神经元参与围绝经期潮热发生的机制

潮热是围绝经期女性最常见的特异性症状,严重危害女性的身心健康和生活质量。由于潮热的发病机制尚未明确,且现有的雌激素替代疗法存在诸多局限和禁忌,故探讨潮热的发病机制并寻找新的治疗靶点尤为迫切和重要。近年研究提示,围绝经期雌激素降低时下丘脑弓状核（ARC）中KNDy神经元异常是引起潮热的关键因素。部分学者认为,ARC中KNDy神经元通过调控促性腺激素释放激素及其下游促黄体生成素的脉冲释放参与潮热的发生;而另有学者认为,ARC中KNDy神经元通过调控下丘脑视前区的正中视前核在潮热发生过程中发挥关键作用。我们就上述两种关于ARC KNDy神经元与潮热发生之间的关系及其参与潮热的可能机制进行总结和概括,为探寻诊治围绝经期潮热的新靶点和新方法奠定理论基础。     

The significance of nucleus raphe dorsalis and centralis for thermoafferent signal transmission to the preoptic area of the rat

Summary Neuronal spike-trains were recorded extracellularly within the preoptic area, which is generally considered the center of information processing for thermoregulation. The neuronal responses were tested by thermal stimulation of the scrotal and abdominal skin of the rat. After a neuron had been identified as warm responsive, electrical stimulation and/or lesion were applied in medial midbrain to test the influence on the preoptic neurons. Post-stimulus-histograms were determined by using 600 single shocks. Furthermore a small area of the medial midbrain was electrolytically lesioned and the thermal response of the neuron was tested again. All lesion, stimulation and recording sites were examined histologically. Electrical stimulation of either nucleus raphe dorsalis or centralis influenced the responsiveness of the recorded preoptineurons. The post-stimulus-histograms predominantly reveal polysynaptic ascending pathways. Lesion of either nucleus raphe dorsalis or centralis abolished the responsiveness of the recorded preoptic neurons. Lesions lateral to these nuclei were ineffective. By this it is concluded that both nucleus raphe dorsalis and centralis are essentially involved in the thermal signal transmission to the preoptic area.     

An analysis of histaminergic efferents of the tuberomammillary nucleus to the medial preoptic area and inferior colliculus of the rat

Summary The efferent projections of the five histaminergic neuronal subgroups in the tuberomammillary nucleus to the medial preoptic area (MPO) and inferior colliculus (IC) were examined by immunocytochemistry with antihistidine decarboxylase (HDC) antibodies combined with retrograde axonal tracing with Fast Blue (FB). The term E groups were used for the histaminergic neuronal subgroups. About 10% of the HDC-immunoreactive (HDCI) neurons were retrogradely labeled after FB injection into the MPO. The labeled neurons were not concentrated in any particular area, but were diffusely distributed bilaterally in all the subgroups. About two-thirds of the labeled neurons were observed on the side ipsilateral to the injection site and one-third on the contralateral side. The percentages of labeled neurons (double-labeled neurons/HDCI neurons) in the five subgroups were not significantly different with each other. The percentages in group E1 and E2 were particularly close, while that in group E4 resembled that in group E5. About 4% of the HDCI neurons were retrogradely labeled after the dye injections into the IC, and about half of the labeled neurons were detected on the ipsilateral side. The percentage of the double-labeled neurons in the five groups were not significantly different. Furthermore, those in E1 and E2, and in E4 and E5 were almost identical, respectively, to the situation following injection of FB into the MPO. These results indicate that each subgroup of histaminergic neurons in the tuberomammillary nucleus has similar efferent projections to the MPO and IC.     

Thermosensitivity of preoptic and anterior hypothalamic neurons in the capsaicin-desensitized rat

Summary Single-unit studies on preoptic and anterior hypothalamic neurons in the capsaicindesensitized rat having deficient thermoregulation against heat showed that the proportion of warm-sensitive and cold-sensitive neurons in a total population of neurons recorded was reduced to about half of the normal.     

Acute fasting decreases sexual receptivity and neural estrogen receptor-alpha in female rats

Acute food deprivation or chronic food restriction suppresses reproduction in female mammals. Although a link between undernutrition and ovarian function is well established in rats, a similar link with reproductive behavior in this species is yet to be described. Therefore, we compared the display of estrous behaviors induced by exogenous steroid hormone treatment in ovariectomized fed and fasted rats. In addition, estrogen receptor-alpha immunoreactivity (ERIR) was measured in fed and fasted animals to determine whether changes in behavior were associated with changes in the number of detectable ERIR-containing cells in several brain regions. Fasting for 74 h decreased lordosis quotients (LQ) and lordosis ratings (LR) in ovariectomized, steroid-primed rats. The number of detectable ERIR cells decreased after a 74-h fast in the mid-region of the arcuate (ARC), paraventricular (PVN) and ventromedial nuclei of the hypothalamus (VMH) and the ventral bed nucleus of the stria terminalis (BST) but did not change in a number of other areas examined. Taken together, these data demonstrate that, similar to the effect on the reproductive-endocrine axis, food deprivation for 74 h suppresses steroid-induced display of lordosis in adult, female rats. Furthermore, this suppression in sexual receptivity is associated with a decrease in ERIR in a number of areas, including the VMH, a region of the hypothalamus known to be critical for the display of reproductive behaviors in female rats.     

Kisspeptin immunoreactive cells of the ovine preoptic area and arcuate nucleus co-express estrogen receptor alpha

Kisspeptins are peptide ligands of the G protein-coupled receptor GPR54, recently shown to be essential to reproductive function. We have raised specific rabbit antisera against a highly conserved 10 amino acid-amidated peptide (kp10) common to all kisspeptin isoforms isolated so far and mapped the distribution of kp10-immunoreactive (ir) cells in the ovine hypothalamus. Kp10-ir cells were predominant in the caudal arcuate nucleus, the dorsomedial nucleus and the medial preoptic area. Numerous varicose kp10-ir fibers were found in the preoptic area where GnRH neurons reside and in the median eminence, seemingly projecting around small capillaries in its external zone. Within the caudal arcuate nucleus, nearly all kp10-ir cells showed an intense estradiol receptor alpha immunofluorescent signal compared with approximately half of kp10-ir cells in the preoptic area. The pattern of distribution of kp10 immunoreactivity in the hypothalamus suggests a role for kisspeptin in the estrogen-dependent regulation of GnRH and LH secretion in the ewe.     

A substance P-containing pathway from the hypothalamic ventromedial nucleus to the medial preoptic area of the rat: an immunohistochemical analysis

The destruction of the hypothalamic ventromedial nucleus, which contains a group of substance P-like immunoreactive neurons, resulted in a marked ipsilateral reduction of these fibers in the medial preoptic area. To test if and to what extent the substance P-like immunoreactive neurons in the ventromedial nucleus project to the medial preoptic area, we applied a sensitive double-labeling method capable of detecting substance P-like immunoreactivity in neurons retrogradely labeled with biotin-wheat germ agglutinin following injection of the tracer in the medial preoptic area. The appearance of many double-labeled cells in the hypothalamic ventromedial nucleus provides strong evidence for the existence of a prominent substance P containing pathway from the ventromedial nucleus to the medial preoptic area. A few doubled-labeled cells were also seen in the lateral hypothalamus, which therefore seems to be an additional source of substance P-like immunoreactive fibers in the medial preoptic area.     

Facilitation of male rat copulatory behavior by electrical stimulation of the medial preoptic area

Lesion studies have demonstrated that the medial preoptic area (MPO) plays a critical role in male rat copulatory behavior. The present study attempted to better localize the neural elements mediating this behavior pattern and to determine the influence of preoptic area stimulation on particular aspects of copulatory behavior. Monopolar stimulating electrodes were implanted in the medial preoptic-anterior hypothalamic continuum or the lateral preoptic-medial forebrain bundle region. The effects of stimulating a particular locus were measured by comparing each animal's behavior on repeated stimulation and control tests. All measures of copulatory activity taken were facilitated by medial, but not by lateral, preoptic stimulation. The most common change produced by MPO stimulation was a reduction in both the number of mounts and intromissions preceding ejaculation. Short-latency approach and mounting of the female and greatly reduced refractory periods were also seen in two MPO animals. No evidence of a post-stimulation inhibition of copulatory behavior resulting from the stimulation itself was seen in these two animals. Most animals in both the medial and lateral groups learned to self-stimulate (SS) using the same 30-sec trains of stimulation as used in earlier tests of copulatory activity. SS rate, stimulation-bound copulation, and degree of facilitation of ejaculation were positively correlated in MPO, but not in lateral preoptic animals.