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Changes of adrenomedullin and its receptor components mRNAs expression in the brain stem and hypothalamus-pituitary-adrenal axis of stress-induced hypertensive rats.

In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the changes in mRNAs levels of preproadrenomedullin (ppADM) gene encoding adrenomedullin (ADM) and the essential receptor components of ADM, calcitonin receptor-like receptor (CRLR), and the receptor activity modifying protein 2 and 3 (RAMP2 and RAMP3) in the medulla oblongata, hypothalamus, midbrain, pituitary gland and adrenal gland of the stress-induced hypertensive rats. It was shown that chronic foot-shock and noise stress for 15 consecutive days induced a significant increase in systolic blood pressure (SBP) and unique changes in ppADM and its receptor components mRNAs in all areas studied. As compared with the control group, the level of ppADM mRNA, normalized against a glyceraldehydes-3-phosphate dehydrogenase (GAPDH) control, was up-regulated in the hypothalamus-pituitary-adrenal (HPA) axis, but down-regulated in the medulla oblongata and midbrain (P<0.01 and P<0.05, respectively). The relative amount of CRLR mRNA was higher in the hypothalamus than that in other areas. The level of CRLR mRNA expression was significantly increased in the medulla oblongata of the stress group (P<0.01), but decreased in the midbrain (P<0.01) as well as hypothalamus(P<0.05), as compared with that of the control group. Chronic stress for 15 consecutive days produced an increase in the level of RAMP2 mRNA expression in the medulla oblongata (P<0.01) and a decrease in the adrenal gland (P<0.01), as compared with the control. No significant stress-related changes in RAMP2 mRNA were observed in the midbrain, hypothalamus and pituitary gland. The amount of RAMP3 mRNA was relatively higher in the midbrain and hypothalamus than that in the medulla oblongata, adrenal gland and adrenal gland. Stress-induced hypertensive rats exhibited an increased RAMP3 mRNA expression in the hypothalamus and pituitary gland (P<0.01 and P<0.05, respectively) and a decrease in the adrenal gland and midbrain (P<0.05). No significant stress-related change in RAMP3 mRAN was observed in the medulla oblongata. Taken together, our results indicate that the significant changes in ppADM and its receptor components mRNAs expression in the HPA axis and autonomic centers may be related to the development of the stress-induced hypertension. Nevertheless, the pathophysiological significance of brain-derived ADM and its receptors in stress and blood pressure regulation and their roles in stress-induced hypertension still await further investigation.

Adrenomedullin↗

Birthdates of the growth hormone releasing factor cells of the rat hypothalamus: an autoradiographic study of immunocytochemically identified neurons.

Growth hormone releasing factor (GRF) neurons in the arcuate nucleus of the hypothalamus and somatostatin (SRIF) neurons in the anterior periventricular region of the hypothalamus act to control the release of growth hormone from the anterior pituitary. To investigate the possibility that the growth-controlling functions of these cells might be compromised by injuries to the developing brain, it is important to know the details of the production and differentiation of these small, specialized cell groups. The overall pattern of cell production in the hypothalamus is known from autoradiographic studies with general nuclear stains, but no data are available on the birthdates (times of final mitoses) of GRF-producing cells. The present study was undertaken to determine when the GRF cells form. Counts of immunocytochemically identified GRF cells labeled on given days were taken from serial coronal sections through the hypothalamus of adult rats labeled on the 10th-17th days of gestation (day of finding a vaginal plug = day 1). As has been shown for the hypothalamus in general, the GRF cells showed a gradient of production from anterior to posterior. The peak of anterior cell proliferation was on day 13, middle cells on day 14, and posterior cells on day 15. These dates are 1 or 2 days earlier than those of GRF-negative cells in the same regions. No lateral to medial gradient of formation was seen in GRF cells. Rather, the laterally placed cells along the base of the brain and those surrounding the ventromedial nucleus formed simultaneously with the GRF cells of the arcuate nucleus. The birthdating results presented here are in agreement with the results of studies of teratogens which suggest that rat postnatal growth is reduced most severely by exposure to neurotoxic agents on days 12 or 13 of gestation. On the basis of data for the whole hypothalamus, such treatments would appear to be too early to interfere with cell production for the arcuate nucleus, but the timing fits the period of vulnerability as defined by the birthdates determined in the present study for the subpopulation of cells destined to produce GRF.

Animals↗

A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats.

In order to determine critical sites within the hypothalamus responsible for the induction and maintenance of wakefulness (W), we performed microinjections of muscimol, a potent gamma-aminobutyric acid (GABA) agonist, in various lateral hypothalamic regions of freely moving cats. We found that bilateral injections of a small amount of muscimol (0.1-1.0 micrograms/0.5 microliters) in the preoptic and anterior hypothalamus and rostral mesencephalic tegmentum resulted in increased vigilance and insomnia. In contrast, microinjections of muscimol in the middle and anterior parts of the posterior hypothalamus induced long-lasting behavioral and electroencephalographic signs of sleep with short latency. The hypersomnia was characterized by a significant increase in both light and deep slow wave sleep (SWS), and a nearly complete suppression of paradoxical sleep (PS). Animals with muscimol microinjections in the ventrolateral part of the posterior hypothalamus, however, exhibited increased SWS followed by a significant increase in PS. When injected into the posterior hypothalamus of insomniac cats pretreated with p-chlorophenylalanine (PCPA), muscimol induced not only SWS but also PS with short latency. The present data thus support the hypotheses that the posterior hypothalamus plays a critical role in the mechanisms of W and that sleep might result from functional blockade of the hypothalamic waking center.

Animals↗

GABA receptors in the posterior hypothalamus regulate experimental anxiety in rats.

Blockade of gamma-aminobutyric acid (GABA) function in the posterior hypothalamus of rats elicits a pattern of physiological and behavioral arousal consisting of increases in heart rate, respiration and blood pressure as well as intense locomotor stimulation and a selective enhancement of avoidance responding. The present study was conducted to assess the possibility that GABA-mediated neurotransmission in the posterior hypothalamus of the rat may regulate anxiety. Male rats were trained in a 'conflict' schedule consisting of a high and a low intensity of punishment ('high' and 'low' conflict) capable of measuring decreases and increases in the level of 'anxiety', respectively. Guide cannulae were stereotaxically implanted bilaterally in the posterior hypothalamus of these rats at sites where microinjection of bicuculline methiodide (BMI) 25 ng caused increases in heart rate under anesthesia. After recovery, they were tested: (1) in the high conflict schedule after microinjection of saline and two doses of the GABAA receptor agonist muscimol; and (2) in the low conflict schedule after injecting saline, the GABAA receptor antagonists, BMI and picrotoxin, and the glycine antagonist, strychnine. Injection of muscimol caused a significant and selective anti-conflict effect while both BMI and, at appropriate doses, picrotoxin produced pro-conflict effects. Microinjection of strychnine into the posterior hypothalamus or muscimol and picrotoxin into the lateral hypothalamus did not influence conflict responding. These results suggest that endogenous GABA acts on GABAA receptors in a discrete area of the posterior hypothalamus to regulate the level of experimental anxiety in rats.

Animals↗

Short-day effects of melatonin on luteinizing hormone secretion in the ewe: evidence for central sites of action in the mediobasal hypothalamus.

Experiments were designed to localize the central sites of action of melatonin involved in the control of seasonal reproduction. Ewes were exposed to long days and received microimplants of melatonin in the preoptic area (n = 9), anterior hypothalamus (n = 4), dorsolateral hypothalamus (n = 4), or mediobasal hypothalamus (n = 12). The effects of implants were determined by comparison with control ewes (untreated or sham-operated, n = 10) and with ewes treated with an s.c. implant of melatonin (n = 8) or ewes subjected to short days (n = 8). All ewes were ovariectomized and treated s.c. with a silastic capsule of estradiol. Melatonin released in the preoptic area as well as in the anterior and lateral hypothalamus did not cause any difference as compared with the controls (no stimulation of LH secretion and no inhibition of prolactin secretion). In contrast, melatonin implanted in the mediobasal hypothalamus caused an increase in LH secretion in 7 of the 12 ewes on Day 53.0 +/- 4.2 after implantation (mean +/- SEM). Their response was not different compared with that of ewes treated s.c. with melatonin or exposed to short days either in terms of timing (Day 56.3 +/- 6.2 and 59.5 +/- 3.1, respectively, for controls) or of amplitude of the LH response. Similarly, melatonin caused only a reduction of prolactin secretion in the mediobasal, s.c., and short-day groups. It is concluded that the mediobasal hypothalamus or the surrounding tissues could be the sites of action of melatonin involved in the control of seasonal reproduction.

Animals↗

Organization of the medial hypothalamus for control of adrenocorticotropin in the cat.

To examine the role and interrelations of areas of the medial hypothalamus in the control of release of ACTH, we stimulated electrically (20-sec train, 200-microamperemeter amplitude at 100 Hz) 695 sites in the hypothalamus of 91 cats anesthetized with chloralose-urethane. Changes in ACTH were measured by RIA. Responses of arterial pressure could not account for changes of release of ACTH. Several ACTH-active areas were defined. The anatomical relations of these areas with known nuclei and pathways then were considered. Two ACTH facilitatory areas and one ACTH inhibitory area were identified in the lateral aspect of the medial hypothalamus. The dorsal facilitatory area appears to be an extension of the lateral division of the dorsolongitudinal fasciculus and to extend medially to join the Fields of Forel, the ventral tegmental area of Tsai, and the parvocellular, paraventricular, and periventricular nuclei. The ACTH inhibitory area appears to be an extension of portions of the central tegmental tract and to extend medially to the posterior hypothalamic area and the dorsal hypothalamic area and ventrally toward the basal hypothalamus. The ventral ACTH facilitatory area appears to be coincident with the medial forebrain bundle and to extend anteroventrally and medially through the supraoptic decussation to the suprachiasmatic, ventromedial, dorsomedial, periventricular, infundibular, and premammillary nuclei. Stimulation of the median eminence led to increased release of ACTH. The results suggest that ascending pathways from the lower brainstem mediating control of ACTH project to discrete areas of the hypothalamus and then converge on the medial basal hypothalamus.

Adrenocorticotropic Hormone↗

[Role of different regions of the hypothalamus in regulating the hypophyseal-adrenal cortex system in rats].

The effect of electrical stimulation of various structures of the medial hypothalamus on the corticosterone level in the peripheral blood was studied in rats with preliminarily destroyed individual areas of the hypothalamus. Injury of various structures of the medial hypothalamus led the first days after the operation to reduction of the response to the stimulation. Two-three weeks after destruction of the anterior and the middle portions of the hypothalamus reactivity of the hypophyseo-adrenocortical system was restored, although not always completely. Only in destruction of the premamillary nuclei there was no restoration of the reaction. A conclusion was drawn that the area of the posterior hypothalamus was of great necessity for functional regulation of the hypophysis-adrenal cortex system.

Adrenal Cortex↗

[Dopamine, noradrenaline and serotonin content in various parts of the hypothalamus in alloxan diabetes].

In male rats with various forms of alloxan diabetes ("prediabetes", latent and manifest diabetes) there was revealed an increase in noradrenaline level in the anterior and the medial-basal hypothalamus. A rise of dophamine content was noted in the hypothalamus of these animals. Serotonin level fell in all the parts of the hypothalamus of males with "prediabetes". The level of immunoreactive insulin on fasting stomach was diminished in manifest alloxan diabetes, particularly in its severe forms. The data obtained suggest the importance of the feedback mechanism between the metabolic disturbances as a result of insulin insufficiency and the changes in the monoamines level in the hypothalamus. The role of certain parts of the hypothalamus in the regulation of insulin secretion is stressed.

Alloxan↗

Organization of the ophidian amygdala: chemosensory pathways to the hypothalamus.

Although recent studies in squamate reptiles have importantly clarified how chemical information is processed in the reptilian brain, how the amygdala relays chemosensory inputs to the hypothalamus to influence chemically guided behaviors is still poorly documented. To identify these chemosensory pathways, the amygdalo-hypothalamic projections, intra-amygdaloid circuitry and afferents from the lateral cortex (LC) to the amygdala were investigated by injecting conjugated dextran-amines into the hypothalamus, amygdala, and LC of garter snakes. The amygdala was divided into olfactory recipient (ventral anterior and external amygdalae), vomeronasal recipient (nucleus sphericus, NS, and medial amygdala, MA), and nonchemosensory (e.g., posterior dorsal ventricular ridge, PDVR, and dorsolateral amygdaloid nucleus, DLA) subdivisions. Rostroventral (LCrv) and dorsocaudal subdivisions of the LC were distinguished. In addition to receiving afferents from the main olfactory bulb, the olfactory amygdala receives afferents from NS and projects to the NS, PDVR, and dorsal hypothalamus. The NS has only a minor projection to the lateral hypothalamus, whereas the MA, which receives afferents from the LCrv and NS, has projections to the ventromedial hypothalamic (VMH) and lateral posterior hypothalamic nuclei. Among the nonchemosensory amygdaloid structures, the PDVR receives afferents from the LCrv and the olfactory amygdala and projects to the VMH, whereas DLA receives afferents from the LCrv and NS, and projects to the periventricular hypothalamus. These results substantially clarify the olfactory and vomeronasal tertiary connections and demonstrate that parts of the nonchemosensory amygdala play a major role in relaying chemosensory information to the hypothalamus.

Amygdala↗

Early development of the hypothalamus of a wallaby (Macropus eugenii).

We have studied the development of the hypothalamus of an Australian marsupial, the tammar wallaby (Macropus eugenii), to provide an initial anatomic framework for future research on the developing hypothalamus of diprotodontid metatheria. Cytoarchitectural (hematoxylin and eosin), immunohistochemical (CD 15 and growth associated protein, GAP-43), tritiated thymidine autoradiography, and carbocyanine dye tracing techniques were applied. Until 12 days after birth (P12), the developing hypothalamus consisted of mainly a ventricular germinal zone with a thin marginal layer, but by P25, most hypothalamic nuclei were well differentiated, indicating that the bulk of hypothalamic cytoarchitectural development occurs between P12 and P25. Strong CD 15 immunoreactivity was found in radial glial fibers in the rostral hypothalamus during early developmental ages, separating individual hypothalamic compartments. Immunoreactivity for GAP-43 was used to reveal developing fiber bundles. The medial forebrain bundle was apparent by P0, and the fornix appeared at P12. Tritiated thymidine autoradiography revealed lateral-to-medial and dorsal-to-ventral neurogenetic gradients similar to those seen in rodents. Dye tracing showed that projections to the posterior pituitary arose from the supraoptic nucleus at P5 and from the paraventricular nucleus at P10. Projections to the medulla were first found from the lateral hypothalamic area at P0 and paraventricular nucleus at P10. In conclusion, the pattern of development of the wallaby hypothalamus is broadly similar to that found in eutheria, with comparable neurogenetic compartments to those identified in rodents. Because most hypothalamic maturation takes place after birth, wallabies provide a useful model for experimentally manipulating the developing mammalian hypothalamus.

Animals↗

Afferent connections to the amygdaloid complex of the rat and cat: II. Afferents from the hypothalamus and the basal telencephalon.

The projections from the basal telencephalon and hypothalamus to each nucleus of the amygdaloid complex of the rat, and to the central amygdala of the cat, were investigated by the use of retrograde transport of horseradish peroxidase (HRP). The enzyme was injected stereotaxically by microiontophoresis, using three different approaches. The ventral pallidum (Heimer, '78) and ventral part of the globus pallidus were found to project to the lateral and basolateral nuclei of the amygdala. The substantia innominata projects diffusely to the entire amygdaloid complex, except to the lateral nucleus and the caudal part of the medial nucleus. The anterior amygdaloid area shows a similar projection field, the only difference being that this structure does not project to any parts of the medial nucleus. The dorsal subdivision of the nucleus of the lateral olfactory tract sends fibers to the ipsilateral as well as the contralateral basolateral nucleus, and possibly to the ipsilateral basomedial and cortical amygdala. The ventral subdivision of the nucleus of the lateral olfactory tract was massively labeled after an injection in the ipsilateral central nucleus, but this injection affected the commissural component of the stria terminalis. The nucleus of the horizontal limb of the diagonal band of Broca connects with the medial, central, and anterior cortical nuclei, whereas the bed nucleus of stria terminalis and medial preoptic area are related to the medial nucleus predominantly. the lateral preoptic area is only weakly labeled after intra-amygdaloid HRP injections. The hypothalamo-amygdaloid projections terminate preponderantly in the medial part of the amygdaloid complex. Thus, axons from neurons in the area dorsal and medial to the paraventricular nucleus of the hypothalamus distribute to the medial nucleus and intra-amygdaloid part of the bed nucleus of stria terminalis. Most of the amygdalopetal fibers from the ventromedial, ventral premammillary, and arcuate nuclei of the hypothalamus end in the medial nucleus, but some extend into the central nucleus. A few fibers from the ventromedial nucleus of the hypothalamus reach the basolateral nucleus. The lateral hypothalamic area projects heavily to the central nucleus, and more sparsely to the medial and basolateral nuclei. The dorsal hypothalamic area and supramammillary nucleus show restricted projections to the central and basolateral nuclei, respectively. There are only a modest number of crossed hypothalamo-amygdaloid fibers. Most of these originate in the ventromedial nucleus of the hypothalamus and terminate in the contralateral medial nucleus. The projections from the basal telencephalon and hypothalamus to the central nucleus of the amygdala of the cat are similar to the corresponding projections in the rat.

Amygdala↗

Organization of central adrenergic pathways: I. Relationships of ventrolateral medullary projections to the hypothalamus and spinal cord.

We studied the organization of projections from the C1 adrenergic and A1 noradrenergic cell groups in the ventrolateral medulla (VLM) to the hypothalamus and the spinal cord by using a combination of retrograde transport of fluorescent tracers and immunocytochemistry. Three issues were addressed. Neurons in the VLM that stain immunohistochemically for phenylethanolamine N-methyltransferase (PNMT) have been assumed to be adrenergic. However, the presence of PNMT-immunoreactive neurons in the hypothalamus that do not stain for tyrosine hydroxylase (TH) prompted us to re-evaluate the VLM by an elution-restaining immunohistochemical procedure. We confirmed that nearly all of the rostral medullary PNMT-immunoreactive neurons also stained for TH. By contrast, in the caudal medulla, very few TH-positive neurons stained for PNMT. Neurons of the C1 group in the rostral VLM project both to the thoracic spinal cord and to the hypothalamus. To determine whether individual C1 neurons send collaterals to the hypothalamus and spinal cord, we injected different-colored fluorescent dyes (diamidino yellow or fast blue) into the thoracic spinal gray matter and either the median preoptic (MnPO) or paraventricular (PVH) nuclei of the hypothalamus. Very few double-labeled neurons were found in the VLM, indicating that hypothalamic and spinal cord projections arise from almost completely independent populations of cells. Approximately half of the neurons projecting to the spinal cord from rostral VLM were not immunoreactive for TH or PNMT, indicating that a substantial part of this projection is noncatecholaminergic. The MnPO and the PVH both receive extensive catecholaminergic inputs from the VLM. We also used fluorescent retrograde tracers to determine whether individual VLM neurons send collaterals to both hypothalamic sites. Approximately 20% of neurons projecting to the MnPO in the rostral two thirds of the VLM also sent collaterials to the PVH, nearly all of these neurons being TH-positive. The collateralization of the VLM catecholaminergic projection to the hypothalamus may provide an anatomical substrate for integration of fore-brain participation in cardiovascular regulation. In contrast, the adrenergic projection from the VLM to the intermediolateral column of the spinal cord arises from a separate population of neurons.

Adrenergic Fibers↗

Evidence for a functional and anatomical relationship between the lateral septum and the hypothalamus in the control of flank marking behavior in Golden hamsters.

Golden hamsters with established dominant/subordinate relationships communicate their social status by rubbing pheromone-producing flank glands against objects in the environment. This behavior, called flank marking, is controlled by vasopressin-sensitive neurons localized to the anterior hypothalamus. Vasopressinergic magnocellular neurons in the nucleus circularis and medial aspect of the supraoptic nucleus are thought to be a source of neurotransmitter for the initiation of flank marking. The present study was undertaken to examine the extrahypothalamic control of flank marking. The anatomical and functional connections between the lateral septum and the vasopressin-containing nuclear groups in and around the anterior hypothalamus were examined by: (1) tracing afferent and efferent connections following microinjection of horseradish peroxidase and Phaseolus vulgaris-leucoagglutinin into the lateral septum, and (2) recording odor-induced flank marking prior to and following ibotenate lesions in the septum. The greatest number of perikarya retrogradely labeled with horseradish peroxidase were found lateral to the anterior hypothalamus and ventral to the fornix in the area of the lateral hypothalamus. The vasopressin-containing nuclear groups, e.g., paraventricular, supraoptic, suprachiasmatic nuclei, and the nucleus circularis, were devoid of labeled perikarya. Nerve terminals anterogradely labeled with Phaseolus vulgaris-leucoagglutinin were primarily localized to the anterior hypothalamus, in and around the nucleus circularis, and the medial aspect of the supraoptic nucleus. The lateral aspect of the supraoptic nucleus was devoid of nerve terminals as were the paraventricular and suprachiasmatic nuclei. The anatomical connections between the lateral septum and the hypothalamus appear to be necessary for the control of flank marking, since the microinjection of ibotenate into this limbic site significantly reduced odor-induced flank marking as compared to control microinjections of 0.9% NaCl.

Animals↗

Galanin immunoreactive neurons in the human hypothalamus: colocalization with vasopressin-containing neurons.

Galanin (GA) is a recently described neuropeptide that has been demonstrated to be widely distributed in the hypothalamus of experimental animals. So far there is no immunohistochemical description of GA in the human hypothalamus and, in particular, no studies of the colocalization of this neuropeptide with other transmitter candidates in the human hypothalamus. We have now investigated this question immunohistochemically by using human brains fixed by vascular perfusion within 24 hours of death. Nerve cell bodies and fibers stained for GA were observed throughout the hypothalamus. Major populations of GA-ir cell bodies were found in the suprachiasmatic, intermediate, supraoptic, paraventricular, arcuate, tuberomammillary, and supramammillary nuclei. Scattered positive neurons were found in the periventricular preoptic area, the posterior hypothalamic nucleus, the lateral hypothalamic area, and zona incerta. A few positive cells were located in the dorsomedial and ventromedial hypothalamic nuclei. The number of GA-ir neurons estimated from three brains was 11,100 +/- 2,400 for the intermediate nucleus, 57,800 +/- 9,100 for the supraoptic nucleus and 47,400 +/- 13,900 for the paraventricular nucleus. GA-ir fibers were widely distributed in the hypothalamus. They were more dense in the periventricular and medial hypothalamic zones, whereas the lateral tuberal nuclei and the dorsolateral part of the supraoptic nucleus contained sparse positive fibers. The mammillary complex contained almost no GA-ir fibers. In the ventromedial tuberal region, GA-ir axons formed bundles travelling down in the infundibular stem. In the median eminence the vascular plexus was wrapped by GA-ir fiber networks. The coexistence of GA with arginine vasopressin (AVP), oxytocin (OXY), and tyrosine hydroxylase (TH) was examined in the supraoptic, paraventricular, and suprachiasmatic nuclei in adjacent paraffin sections. Neurons containing both GA and AVP were very common in the supraoptic nucleus and also occurred in the paraventricular and suprachiasmatic nuclei. The supraoptic and paraventricular nuclei also contained some neurons immunoreactive for both GA and OXY. Neurons positive for GA and TH were rare. The topographic distribution of GA-ir neuronal structures in the hypothalamus and the colocalization of GA, principally with AVP and to a lesser extent with OXY, in some hypothalamic nuclei constitute anatomical evidence that this neuropeptide may be involved in the regulation of endocrine, autonomic, and behavioural homeostatic responses.

Aged↗

Histaminergic system in the cat hypothalamus with reference to type B monoamine oxidase.

It is known that histamine (HA) and type B monoamine oxidase (MAO-B), an enzyme involved in its metabolism, are present in the posterior hypothalamus, but the sites where MAO-B intervenes in HA metabolism remain uncertain. The present study examined and compared the detailed distribution and morphology of neurons immunoreactive to HA (HA-ir) and MAO-B (MAO-B-ir) in the cat hypothalamus. HA-ir neurons were localized almost exclusively in the posterior hypothalamus with the largest group in the tuberomammillary nucleus and adjacent areas. MAO-B-ir staining was detected in the vast majority of HA-ir neurons, suggesting that the degradation of tele-methylhistamine (t-MHA), the direct metabolite of HA, may occur within these cells. Nevertheless, a few HA-ir cells showed no detectable or very weak MAO-B-ir labeling; a small group of neurons containing MAO-B alone was detected in the area dorsolateral to the caudal part of the arcuate nucleus. Numerous HA-ir axons and terminal-like structures were distributed unevenly in virtually all hypothalamic regions. One of their principal trajectories ascended through the ventrolateral part of the hypothalamus and rostrally formed an axon column, which ascended into the preoptic area and contributed fibers to the diagonal band of Broca and bed nucleus of the stria terminalis. Other HA-ir axons passed laterally, dorsal to the zona incerta or ventrally through a narrow zone dorsal to the optic tract. Numerous long HA-ir axons coursed dorsomedially from the ventrolateral posterior hypothalamus to the dorsal hypothalamic area. Many are oriented vertically to the thalamus in the midline. MAO-B-ir axons and fibers were detectable throughout the hypothalamus and overlapped the areas distributing HA-ir fibers. They were, however, weaker in staining intensity and apparently fewer than the HA-ir fibers. MAO-B-ir glial cells were numerous in all hypothalamic structures rich in HA-ir fibers. These results suggest that the metabolism of t-MHA may also occur within HA terminals and glial cells.

Animals↗

Interconnections between the neuroendocrine hypothalamus and the central autonomic system. Geoffrey Harris Memorial Lecture, Kitakyushu, Japan, October 1998.

Tract-tracing techniques in combination with immunohistochemistry and in situ hybridization were used in intact and operated rats (hypothalamic lesions, transections of neuronal pathways) to localize and characterize neuronal connections between the hypothalamus and autonomic centers. Viscerosensory and somatosensory signals which relay in the spinal cord and the medulla oblongata reach the hypothalamus through various catecholaminergic and noncatecholaminergic neuronal pathways. Vice versa, the hypothalamus influences autonomic activities through humoral and neurohumoral pathways. Descending hypothalamic efferents carry feedback signals to viscerosensory and brainstem catecholaminergic neurons and regulatory inputs to parasympathetic (dorsal vagal nucleus) and sympathetic (thoracolumbar intermediolateral cell column) preganglionic neurons. These fibers arise mainly from neurons of the paraventricular, arcuate, perifornical, and dorsomedial nuclei and the lateral hypothalamus. The major neuroanatomical observations are the following: (1) pathways between the hypothalamus and autonomic centers are bidirectional: the ascending and descending fibers may use the same avenues; (2) the descending axons are mainly peptidergic (CRF, vasopressin, oxytocin, somatostatin, enkephalin, POMC, and cANP), while the ascending fibers are both peptidergic (enkephalin, NPY, neurotensin, dynorphins) and catecholaminergic; (3) descending hypothalamic axons terminate directly on the sensory, preganglionic, and catecholaminergic neurons in the medulla and the spinal cord; (4) hypothalamic projections to the autonomic centers are always bilateral; (5) while medullary autonomic and catecholaminergic fibers innervate hypothalamic neurons directly, spinohypothalamic axons are relayed on neurons in the lateral hypothalamus.

Animals↗

In vivo release of endogenous GABA in the cat hypothalamus.

The posterior hypothalamus of anaesthetized cats was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of endogenous GABA from the hypothalamus into the superfusate was studied. The resting release of GABA varied rhythmically, since phases of high rate of release were separated from each other by phases of low rate of release. The time interval between two adjacent phases of high rate of release was about 70 min. Electrical stimulation of the posterior hypothalamus with the tip of the cannula enhanced the rate of release of GABA in a frequency-dependent way. Superfusion of the hypothalamus with CSF which contained a high concentration of potassium and a low concentration of sodium increased the rate of release of GABA; this effect was dependent on the presence of calcium ions in the superfusing fluid. Pretreatment of the cats with reserpine reduced the levels of GABA in hypothalamus and rest of brain and the concentration of GABA in the superfusate as well. Stimulation of the locus coeruleus with a bipolar electrode elicited an increased release of GABA in the hypothalamus.

Animals↗

Presence of beta-adrenoreceptors in the hypothalamus; their importance for the pressor response to hypothalamic stimulation.

The posterior hypothalamus of cats anaesthetized with pentobarbital sodium was superfused and electrically stimulated with a push-pull cannula. Superfusion of the hypothalamus with (+/-)-, (-)-propranolol, sotalol, practolol or metoprolol caused a concentration-dependent inhibiton of the pressor response to hypothalamic stimulation. (+/-)-Propranolol and a procaine concentration equi-anaesthetic to the concentration of (+/-)- and (-)-propranolol were ineffective. Lower concentrations of propranolol and metoprolol were needed to inhibit the pressor response than of sotalol or practolol. Superfusion with practolol and tolazoline impaired the pressor response to a greater extent than did superfusion with each of the drugs alone. Hypothalamic superfusion with isoproterenol elicited a concentration-dependent enhancement of the rise of blood pressure during electrical stimulation of the hypothalamus. It is concluded that beta-adrenorecptors are present in the posterior hypothalamus and that they are involved in the pressor response elicited by electrical stimulation of the hypothalamus. Propranolol and metoprolol seemed to possess a higher affinity to the beta-receptors of the hypothalamus than sotalol or practolol.

Animals↗