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Distribution and co-localization of nitric oxide synthase and argininosuccinate synthetase in the cat hypothalamus.

Argininosuccinate synthetase (ASS) and nitric oxide synthase (NOS) comprise part of the cyclic metabolic pathway to produce nitric oxide (NO). ASS is one of the arginine synthesis enzymes which synthesizes argininosuccinate from aspartate and citrulline, and NOS forms NO and citrulline from arginine. This study examines the localization of ASS and NOS in the cat hypothalamus using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and immunohistochemistry against ASS and NOS. NADPH-d positive and/or ASS-immunoreactive neurons were localized in the following areas: the anterior hypothalamic area, the anterior hypothalamic nucleus, the supraoptic nucleus, the suprachiasmatic nucleus, the periventricular complex, the paraventricular nucleus, the parvocellular nucleus, the lateral hypothalamic area, the dorsomedial hypothalamic nucleus, the dorsal hypothalamic area, the posterior hypothalamic area, and the supramammillary nucleus. NOS and ASS double-labeled neurons were found in the anterior hypothalamic area, the supraoptic nucleus, the central part of the paraventricular nucleus of the hypothalamus, the lateral hypothalamic area, ventral part of the parvocellular hypothalamic nucleus, the posterior hypothalamic area, and the supramammillary nucleus. Double-labeled neurons in the hypothalamus comprised 20.7-32.0% of ASS-immunoreactive neurons and 10.2-26.3% of NOS-immunoreactive neurons. The results suggest the existence of the 'NO cycle' in situ and the physiological importance of NO and argininosuccinate in several regions of the cat hypothalamus.

Animals↗

Morphogenesis of the hypothalamus and hypophysis: their association, dissociation and reassociation before and after "Rathke".

Recent progress in the experimental morphology of the development of amphibian pituitary gland is reviewed. A series of transplantation experiments were carried out using wild-type embryos of the toad as a donor and albino embryos as a recipient. Melanin granules in the wild-type cells allowed tracing of the developmental fate of the grafts as a visible cell marker. These studies have demonstrated that the pituitary gland is not a stomodeal derivative, as it has long been believed to be under the name of "Rathke's pouch". The adenohypophysis is of neural origin. The anterior part of the neural ridge (ANR) in the neuroectoderm of the open neurula gives rise to the whole adenohypophysis, i. e., pars distatis, pars intermedia and pars tuberalis. The presumptive hypothalamus is apposed caudally to the pituitary primordium. A part of the ANR contributes neurons to the preoptic hypothalamus even after closure of the neural tube. The anlagen of the olfactory system, which include the nasal epithelia and the olfactory bulbs, are situated on both sides of the pituitary primordium in the neural ridge. In both hypothalamic-hypophyseal and olfactory systems, the peripheral and central parts derive from closely affiliated cell populations, suggesting their clonal relationships. Development of the hypophysis and hypothalamus is interdependent. On one hand, a connection with the embryonic hypothalamus is essential for the pituitary proopiomelanocortin cells to develop. On the other hand, neither the hypothalamic median eminence nor its axonal supply develops without the presence of the pituitary primordium. Novel aspects of the ontogeny and phylogeny of these organs are discussed with special reference to the role of the neural ridge in the generation of a spectrum of chemoreceptive organs.

Animals↗

Diabetes induced by streptozocin results in a decrease in immunoreactive beta-endorphin levels in the pituitary and hypothalamus of female rats.

Immunoreactive beta-endorphin (IR-BE) was measured by radioimmunoassay in the anterior pituitary (AP), neurointermediate lobe of the pituitary (NIL), and hypothalamus of female rats 4 wk after being made diabetic by a single injection of streptozocin (STZ). STZ-induced diabetes resulted in a significant reduction in the content and concentration of IR-BE in the AP and the content of IR-BE in the hypothalamus. Total hypothalamic protein was also significantly diminished. IR-BE levels in the NIL were unchanged. Column chromatography indicated that the reduction in IR-BE in the AP of the diabetic female rats represented a decrease in peptides that co-eluted with beta-endorphin and beta-lipotropin. In the hypothalamus, the reduction in IR-BE was represented solely by a decrease in a peptide co-eluting with beta-endorphin. Beta-lipotropin was not detectable in the hypothalami of control or diabetic female rats. These results suggest that, in the rat, diabetes may produce alterations in the mechanism(s) that regulate endogenous opiate levels in the pituitary and hypothalamus.

Animals↗

Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting.

The responsiveness of the hypothalamus to the inhibitory effects of leptin on food intake and body weight is influenced by multiple factors, including deficiency of either leptin or leptin receptors (Ob-R). To investigate whether altered expression of Ob-R in the hypothalamus could potentially contribute to altered leptin sensitivity, we performed in situ hybridization with riboprobes that detected either mRNAs encoding both the long (Ob-Rb) and short (Ob-Ra) splice variants or mRNA encoding only Ob-Rb. In the arcuate nucleus, mRNA encoding Ob-Rb, the predominant signaling form of the receptor, was 2.3 times greater in obese db/db and ob/ob mice than in lean +/ob controls (P < 0.01). In ob/ob mice, systemic administration of leptin reduced Ob-Rb mRNA content of the arcuate nucleus by 30% compared with saline-treated, pair-fed controls (P < 0.05). A 48-h fast increased Ob-Rb mRNA levels in the arcuate nucleus of normal and neuropeptide Y (NPY)-knockout mice (P < 0.01), although the effect was greater in the NPY-knockout mice (400 vs. 247%, P < 0.05). In addition, Ob-Rb mRNA hybridization was elevated by 40% in the arcuate nucleus (P < 0.05) and by 75% in the ventromedial nucleus (P < 0.05) of rats fasted 48 h. The results suggest that expression of Ob-Rb mRNA in the hypothalamus is sensitive to genetic and physiological interventions that alter circulating leptin levels, and that overexpression of Ob-Rb in the hypothalamus may contribute to increased leptin sensitivity.

Animals↗

Benzodiazepine binding sites in the human hypothalamus. Autoradiographic study.

Using in vitro labelling and autoradiographic techniques, we have analyzed the fine and the detailed distribution of benzodiazepine binding sites in the post-mortem human hypothalamus. Binding sites were labelled in mounted tissue sections from adult brains, using the selective high affinity ligand [3H]-Flunitrazepam. A heterogeneous distribution of benzodiazepine binding sites was found throughout the rostrocaudal extent of human hypothalamus. The autoradiographic labelling was shown in the three hypothalamic parts, i.e., anterior, mediobasal and posterior levels. At the anterior level, the highest densities were present in the diagonal band of Broca, the preoptic area (medial and lateral parts) and the septohypothalamic nucleus. At the mediobasal hypothalamic level, the highest densities were mainly localized in the ventromedial nucleus, whereas the other structures were moderately labelled with [3H]-Flunitrazepam. The mammillary complex as well as the posterior hypothalamic area represented the most heavily labelled structures in the posterior hypothalamus. The results obtained in this study, indicate the presence of a large and heterogeneous distribution of benzodiazepine binding sites in human adult hypothalamus. This could support their implication in the control of distinct neural functions (like neuroendocrine role).

Adult↗

[Effect of selective lesions in hypothalamus on bilateral synchronized bursts of rat oxytocin neurons].

In order to clarify the location of the center for synchronized milk-ejection bursts of magnocellular oxytocin neurons in the hypothalamus, the bursts of these neurons were recorded extracellularly in lactating rats with selectively-cutting lesions of the middle brain or hypothalamus. Results showed that unilateral transection of the middle midbrain above the ventral tegmentum did not block the synchronized bursts on both sides; however, the synchronized bursts disappeared after unilateral transection through the middle of the medial hypothalamus. These results suggest that the area from the middle part of the midbrain to that of the hypothalamus does play a crucial role in the synchronized milk-ejection burst.

Animals↗

[Cardiovascular effects of direct action of potassium and calcium ions on the hypothalamus].

In experiments on adult rats, using the stereotaxic technique of cannulas implantation, the changes in arterial pressure, contraction rate and bioelectric activity of the heart were studied by means of introducing small doses of potassium and calcium chlorides into the zones of the anterior and posterior hypothalamus and into the CSF of the 3rd ventricle of the brain. The injections of potassium chloride were found to produce an elevation of the arterial pressure, tachycardia and irregular changes in the voltage and pattern of the waves of the ventricular complex of ECG; similar injections of the structures of the anterior hypothalamus to the action of calcium was noted, while the posterior appeared more sensitive to potassium. It was concluded that direct stimulations of the posterior hypothalamic structures with potassium and calcium ions produce a more lasting tonic effect on the haemodynamics than their effect upon the anterior hypothalamus. It is suggested that the hypothalamus is an important level of not only the reflex, but also of the direct neurogenic regulation of the haemodynamic parameters.

Animals↗

[Effect and mechanism of active fraction A guizhi decoction on dual-directional thermoregulation: effect on heat shock protein in hypothalamus of rats].

OBJECTIVE: To investigate the effect of active fraction A in Guizhi Decoction (Fr.A) on dual-directional thermoregulation and its mechanism of influencing heat shock protein (HSP) in hypothalamus. METHOD: Using Western blot method to measure HSP of hypothalamus in febrile and hypothermal rats. RESULTS: Regulating the body temperature in dual-direction, Fr.A could antagonize the decrease of HSP contents of hypothalamus in hypothermal rats induced by aminopyrine, and abate the HSP content in febrile rats induced by yeast. CONCLUSION: Fr.A adjusts the body temperature through regulating the contents of HSP of hypothalamus in febrile and hypothermal rats.

Animals↗

[Effects of flavonoids from semen Cuscutae on changes of beta-EP in hypothalamuses and FSH and LH in anterior pituitaries in female rats exposed to psychologic stress].

OBJECTIVE: To study the mechanism of flavonoids from Semen Cuscutae (FSC) improving the ovarian endocrine functions. METHODS: (1) FSC were obtained from the semen of Cuscuta chinensis through solvent extraction and polyamide columnar chromatography. (2) Sound, light and electricity were combined into a stressful stimulas to induce psychologic stress in female rats. (3) To observe the effects of FSC on the changes of beta-EP in hypothalamuses, FSH and LH in anterior pituitaries and the changes in pituitary morphology in female rats exposed to psychologic stress. RESULTS: FSC decreased the content of beta-EP in hypothalamuses, and increased the numbers of basophilic cell and content of LH in anterior pituitaries, didn't change content of FSH in anterior pituitaries in female rats exposed to psychologic stress. CONCLUSION: FSC decreases the contents of beta-EP in hypothalamuses and increases contents of LH in anterior pituitaries in female rats exposed to psychologic stress, which may be one of the mechanism of FSC improving hypothalamus-pituitary-ovary axis.

Animals↗

Radiographical investigations of organic lesions of the hypothalamus in patients suffering from neurogenic pulmonary edema due to serious intracranial diseases: relationship between radiographical findings and outcome of patients suffering from neurogenic pulmonary edema.

Radiographical investigations of the hypothalamus by computerized tomography (CT) have rarely been performed despite the fact that the damage to the hypothalamus owing to serious intracranial organic diseases may cause neurogenic pulmonary edema (NPE). We presented 22 consecutive cases of patients suffering from NPE caused by serious intracranial organic diseases and investigated the relationship between NPE and abnormal radiographical findings of the hypothalamus. In 11 cases, organic lesions were noted in the hypothalami and 10 of these patients died of NPE (91.0%). In contrast, of the remaining 11 cases without significant radiographical findings of organic lesions in the hypothalami, only 2 patients were lost (18.2%). In general, various factors including systemic ones are considered to contribute to the prognosis of the patients suffering NPEs caused by serious intracranial diseases. It was concluded that hypothalamic damage was not always found by radiograph in patients with NPE due to critical intracranial diseases, but once abnormal findings in their hypothalamus of these patients were noted, their prognosis would become significantly poor (p < 0.05).

Adult↗

[Expression changes of nitric oxide synthase mRNA of hypothalamus after sleep deprivation in rats].

OBJECTIVE: To study the effects of rapid eye movement sleep (REMS) deprivation on the expression of mRNA coding for neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) of hypothalamus in rats. METHOD: Flower pot technique was adopted to deprive the REMS of Sprague-Dawley rats for 24 h, 48 h and 72 h respectively. The expression of mRNA coding for nNOS or iNOS of hypothalamus in rats was assayed by reverse-transcription polymerase chain reaction (RT-PCR). RESULT: The amount of nNOS mRNA was significantly higher in 24 h REMS deprivation group (P<0.01), then the amount was lowered in 48 h deprivation group and became significantly lower in 72 h deprivation group than that in the control group (P<0.05). There was low expression of iNOS mRNA of hypothalamus in rats, and there was no difference in the expression of iNOS mRNA among 24 h, 48 h REMS deprivation and the control groups. But the expression was significantly increased in 72 h REMS deprivation group (P<0.01). CONCLUSION: Deprivation of REMS increased the expression of nNOS and iNOS mRNA of hypothalamus. Excessive nitric oxide (NO) might be a major factor resulting in not only the sleep rebound phenomenon but also the injury of human function caused by sleep loss directly or indirectly by other sleep factors.

Animals↗

Does lineage determine the dopamine phenotype in the tadpole hypothalamus?: A quantitative analysis.

The ancestry of dopaminergic (DA) neurons in the Xenopus laevis hypothalamus was investigated by combining intracellular lineage dye injections of 16- and 32-cell blastomeres with the immunofluorescent detection of tyrosine hydroxylase at tadpole stages. At these stages, DA neurons in the hypothalamus comprise a discrete nucleus that contains from 22 to 45 cells on each side [mean = 32.6 +/- 6.6 (SD)]. The DA nucleus descends from only four of the 16-cell blastomeres. The two dorsal midline blastomeres (D1.1) are the major progenitors, and in all embryos studied they contributed to the DA nucleus. The two dorsal lateral blastomeres (D1.2) contribute to the DA nucleus in only about half of the embryos. Thus, the DA nucleus descends only from a discrete group of progenitors, and the participation of some of the progenitors in the DA lineage is only probabilistic. The number of DA neurons generated by the same blastomere varied greatly in different animals. This variation in cell number correlated with the degree of coherence and the density of the clone in the hypothalamus, rather than with clonal ancestry. Bilateral deletion of the major 32-cell progenitor (D1.1.1) resulted in a nearly complete restitution of the DA nucleus in 74% of the embryos that successfully completed gastrulation and neurulation. In the rest, the hypothalamus was smaller than normal or missing, and the DA nucleus was significantly reduced in size or absent. These results show that the DA nucleus can be restored after its normal lineage is deleted, but complete regulation is not always accomplished. Several blastomere progenitors dramatically altered their contribution to the DA nucleus after D1.1.1 ablation, including two blastomeres that normally do not contribute to the DA lineage. Thus, the fate to produce DA neurons is not determined at cleavage stages.

Animals↗

The anatomy and embryology of the hypothalamus in relation to hypothalamic hamartomas.

The hypothalamus is involved in a variety of autonomic, endocrine, neurological and behavioural functions including temperature, osmostatic and autonomic nervous system regulation, pituitary, thyroid, adrenal and gonadal control, thirst, appetite and weight control, memory and emotional behaviour including aggression and laughter, and biological (circadian) rhythms. The functional anatomy of the hypothalamus and its major afferent and efferent neurological connections are described, with particular reference to hypothalamic hamartomas (HH), gelastic seizures, MRI of the hypothalamus, and potential effects of surgery for HH. Normal development of the hypothalamus is reviewed in relation to models of forebrain development, descriptive hypothalamic embryology and the importance of known transcription factors. Potential environmental antecedents to HH development are discussed, and the significance for sporadic, isolated HH of several syndromes associated with HH is explored.

Animals↗

[Evoked activity of the cat hypothalamus and amygdala under food motivation and in emotional stress].

Amplitude-latency characteristics of auditory evoked potentials (EPs) recorded in bilateral points of the lateral hypothalamus and amygdala were studied under food motivation, in emotional stress (presentation of dogs) and tentative reactions. In the state of hunger, as compared with safety, the latencies of P1, N2 components of EP in hypothalamus, and P1, N2, N3 in amygdala were decreased and their amplitudes were changed. Changes in the left side of both structures were more pronounced. During presentation of dogs, decreases of latencies of all EP components including N1 occurred in hypothalamus and amygdala, changes in hypothalamic potentials were more pronounced on the right side, whereas in the amygdala--on the left side. During tentative responses to emotional-neutral stimuli, the latency of EP increased. It was concluded that sensory reactivity of hypothalamus and amygdala increased in motivational-emotional states. It was supposed that the side of dominance of structure may be related both to the factors of active or passive behavior during fear and the genesis of emotion (motivational or informational).

Amygdala↗

[Studies of Calotes versicolor on the sexual function amelioration mechanism by hypothalamus inhibition in immature male rats].

OBJECTIVE: To study the amelioration mechanism of Calotes versicolor petroleum ether extracts (CVPEE) on hypothalamus inhibition sexual function induced by morphine in immature male rats. METHODS: The hypothalamus inhibition induced by morphine in immature male rats was used as model of the testis reproductive functional disturbance. The rats was given CVPEE for 21 days. The levels of testosterone (T) and follicle stimulating hormone (FSH) in serum were determined by the radio-immunoassay. The nitrogen monoxide (NO) contents in serum and penis tissue were determined by nitrate reductase method. The sexual organ and auxiliary sexual organ coefficient were calculated and the histopathological changes in the testes and epididymides were observed with microscope. RESULTS: CVPEE groups (low and high dosage groups) significantly enhanced the level of serum T, compared with model group (P < 0.05); the low dosage group decreased obviously the level of FSH. CVPEE had the tendency to increase NO contents in serum and penile tissue. The microscopic examination results showed that the testis tissue in CVPEE group was damaged more gently than those in model group. CONCLUSION: CVPEE can enhance the level of serum T and NO contents in penile tissue, improve the sexual functional disturbance in hypothalamus inhibition induced by morphine in immature male rats. It indicated that CVPEE had the effects by the hypothalamus-hypophysis-gonad axial function.

Androgens↗

[Effects of electroacupuncture on CRH, IL-2 and beta-EP contents in the hypothalamus in the rat of adjuvant arthritis].

OBJECTIVE: To explore Mechanisms of electroacupuncture in anti-inflammation and immunoregulation, and to compare differences among "Dazhui" (GV 14), "Mingmen "(GV 4) and non-acupoint in these actions. METHODS: Adjuvant arthritis rat model was made. The rats were divided into 5 groups: normal group, model group, "Dazhui" (GV 14) electroacupuncture group, "Mingmen" (GV 4) electroacupuncture group and non-acupoint electroacupuncture group. Effects of electroacupuncture on local joint inflammation and corticotropin-releasing hormone (CRH), beta-endorphin (betaEP) and interleukin-2 (IL-2) contents in the hypothalamus were observed and differences of the actions among different points were compared. RESULTS: CRH content in the hypothalamus in the "Dazhui" (GV 14) electroacupuncture group decreased as compared with the model group (P < 0.05); there was no significant change in beta-EP and IL-2 contents of the hypothalamus in the 3 electroacupuncture groups as compared with the model group (P > 0.05); there was positive correlation between CRH and IL-2 contents, and between IL-2 and beta-EP contents in the hypothalamus. The swelling rate of the toe in the "Dazhui" (GV 14) group and the "Mingmen" (GV 4) group was lower than that in the non-acupoint group (P < 0 05). CONCLUSION: Electroacupuncture exerts anti-inflammation and immunoregulation possibly via regulation of CRH, IL-2 and beta-EP each other, and the anti-inflammation action of "Dazhui" (GV 14) and "Mingmen" (GV 4) is stronger than that of non-acupoint.

Acupuncture Points↗

Brain and behaviour: morphological and functional aspects of the hypothalamus in the rat.

In a short historical overview some developments in the behavioural research of the hypothalamus of the rat are introduced. Especially the ventromedial and the lateral hypothalamus have received much attention in the past. Numerous different behavioural effects have been described as the result of some kind of activation or inactivation of parts of the hypothalamus in the rat. Questions concerning the topographical distribution and the specificity of the effects observed, are addressed in the later parts. These behavioural observations were very important for the comparison with our anatomical observations concerning the hypothalamus, including the topographical organization of some afferent and efferent relationships. Non-synaptic or paracrine communication may play an important role in the hypothalamic effects on the organization of behaviour.

Animals↗

Leptin and long form of leptin receptor genes expression in the hypothalamus and pituitary during the luteal phase and early pregnancy in pigs.

Leptin is a polypeptide that plays a key role in the regulation of energy homeostasis and is also linked, among others, to mechanisms controlling reproductive processes. Data concerning the involvement of leptin in controlling reproductive functions at the level of hypothalamus and pituitary in the pig are limited. Therefore, in the present study, an expression of genes coding for leptin and long-form leptin receptor (Ob-Rb) was determined by a semiquantitative reverse transcription polymerase chain reaction (RT-PCR) in the discrete areas of porcine hypothalamus (medial basal hypothalamus - MBH, preoptic area - POA, stalk median eminence - SME) and pituitary (anterior - AP and posterior/neural - NP parts) during the luteal phase of the cycle (days 10-12 and 14-16) and two early stages of pregnancy (days 14-16 and 30-32). Leptin gene expression in MBH was found to be higher in the mid- than in the late-luteal phase, whereas in other structures studied it remained unchanged during these periods. More pronounced differences were noted in expression of Ob-Rb gene, which was increased in MBH, AP and NP during the late-luteal phase in comparison to the mid-luteal one, whilst the relationship in the POA was reversed. In turn, during pregnancy, leptin gene expression in all tested areas of hypothalamus as well as Ob-Rb mRNA content in MBH were higher on days 30-32 than on days 14-16. In contrast, in the anterior pituitary, Ob-Rb gene expression was more pronounced on days 14-16 than during later stage of pregnancy. Comparison of leptin and Ob-Rb mRNA content in studied structures between the mid-luteal phase and days 14-16 of pregnancy revealed inhibition of leptin gene expression in almost all examined tissues (MBH, POA, SME, NP) during early pregnancy whereas Ob-Rb gene expression was inhibited in POA but stimulated in both parts of the pituitary during this stage. In summary, obtained results suggest an involvement of leptin in the regulation of hypothalamic-pituitary axis activity during both the luteal phase of the cycle and early pregnancy in pigs.

Animals↗