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[The hypothalamo-hypophyseo-ovarian systems in rats after deafferentiation of the mediobasal hypothalamus].

Complete surgical deafferentation of the medio-basal hypothalamus (MBH) in rats entails suppression of the oestrus cycle as well as a decrease of luteinizing hormone, estrogens and progesterone release into the blood due to a sharp fall of the luliberine content in the median eminence and arquate nuclei. No connection was revealed between the character of oestrus disturbances and the extent of damage or isolation of the arquate, ventromedial, supraoptic and paraventricular nuclei and the amount of Homori-positive neurosecreted in the MBH. In development of permanent diestrus the MBH isolation was more complete than in the preservation of irregular cycle. The luliberine seems to be produced mainly in the anterior hypothalamus of rats whereas the MBH alone fails to maintain even its tonic secretion. Even in complete surgical isolation of the MBH, separate fibers of the luliberinergic cells penetrate into the MBH maintaining there a certain amount of luliberin and preserving synthesis of the luteinizing hormone in the hypophysis with its decreased release into the blood.

5-Hydroxytryptophan↗

[Modulation of the activity of neurons of Deiter's nucleus upon electric stimulation of the hypothalamus and limbic structures of the brain].

In immobilized cats, stimulation of the lateral hypothalamus facilitates the activity of vestibular neurons; stimulation of the hypothalamic ventro-medial nucleus and dorsal hippocampus suppresses the unit activity, mainly. The effects of stimulation of the basolateral amygdalar nucleus were excitatory as well as inhibitory. Prevalence of the long-latency tonic responses indicates that the modulating effects of the hypothalamus and limbic structures are fulfilled through either mesencephalic RF or thalamic nuclei.

Amygdala↗

[Effect of unilateral extirpation of the superior cervical sympathetic ganglion and electric stimulation of the posterior hypothalamus on the rate of reflex conditioning in the dog].

The influence of the sympathetic nervous system and the posterior hypothalamus on the rate of conditioning and the magnitude of conditioned reflexes was studied on dogs by motor defensive method. Extirpation of the superior cervical sympathetic ganglion reduced the conditioned reflex magnitude, delayed the elaboration of positive reflexes facilitating the formation of the inhibitory process. Stimulation of the posterior hypothalamus with electrical current of medium strength (50 mcA) promoted the enhancement of positive conditioned reflexes, and while not substantially affecting the rate of their formation, facilitated elaboration of internal inhibition.

Animals↗

[Intrahypothalamic connections of the rostral and caudal portions of the hypothalamus (retrograde axonal horseradish peroxidase transport study)].

Unilateral injections of 0.2--0.3 mkl 30% horseradish peroxidase (HP) Sigma VI were performed to 4 groups of rats: into the medial and lateral preoptic areas, into the medial and lateral areas of the caudal hypothalamus. After all injections performed the predominant amount of HP-positive neurons was found to situate ipsilaterally in the middle (tuberal) hypothalamic area, mainly in the frontal and lateral hypothalamic fields. Owing to the data obtained, it is possible to conclude that the tuberal hypothalamic areas mentioned are the source of the afferent innervation within the hypothalamus for its rostral and caudal parts.

Afferent Pathways↗

[Functional interactions between the rabbit hypothalamus and neocortex].

In acute experiments on rabbits under chloralose-nembutal anaesthesia, studies have been made on the distribution and the pattern of the evoked potentials (EP) in neocortical structures of the brain cortex during electrical stimulation of different hypothalamic nuclei. It was found that during stimulation of the supramammilar area of the hypothalamus, the focus of maximum activity of cortical responses of the negative-positive configuration is localised in the median parts of precentral agranular region. During stimulation of the posterior hypothalamic area, the EP were of the positive-negative-positive type. Registration of the EP in different cortical layers during stimulation of the posterior hypothlamic nuclei showed that from 100 to 100 micrograms the amplitude of EP components decreases, whereas at the level of 600 mu the inversion of the EP takes place. At the depth of 1.800 mu the EP elicited by stimulation of the posterior hypothalamus had a form of a positive oscillation with a long latent period. It is concluded that the posterior hypothalamic nuclei have a vast representation in rabbit neocortex, this representation being realized by both polysynaptic and olygosynaptic systems of connections.

Animals↗

[Effect of electrostimulation of the medial portion of the hypothalamus of cats on features of sciatic nerve fiber restructuring in experimental neuritis].

In order to study the processes of rearrangement in nerve fibers of the ischiatic nerve and its nervi nervorum at experimentally induced neuritis, the middle part of the hypothalamus was electrically stimulated in 74 mature cats. Twenty three cats were electrically stimulated with alternating current of a rectangular form, 50 Hz 1 m/sec, 1.5 V, for 30 min on each side of the hypothalamic subtubercle. Seven days after electrode implantation, the experimental neuritis was produced by inserting aseptic mica plates subepineurally into the ischiatic nerve. Samples of the nerve stem were taken from the traumatized area and histological sections and film preparations were made. The material was treated after Foot, Ramon y Cajal, Rasskazova, Bielschowsky-Gross-Kampos, Sokoliansky, McManus. As demonstrated the analysis of the preparations, at early stages of the experiments the nerve fibers were preserved better under the electrostimulation than in the intact hypothalamus. However, by the 60th day, resulting from the pathology of the diencephalon, some distrophic changes developed in the peripheral nerve. Lateral branching processes were forming on the axonal cylinders. Nervi nervorum were spreading and forming long and dense wrappings around the endoneural sheaths where they terminated with loops simulating Perroncito's spirals.

Animals↗

Feeding behavior in the rat with isolated medial hypothalamus.

After complete, unilateral, frontolateral, dorsal isolation of the medial hypothalamus, VMH included, or fornix section above the hypothalamus, total food consumption and diurnal pattern of food intake were followed 85 days postoperatively. It is suggested that the saftety signals are generated not only in VMH nucleus, but in a VMH-retrochiasmatic region located anteriorly to the VMH.

Animals↗

Postmortem anterograde tracing of intrahypothalamic projections of the human dorsomedial nucleus of the hypothalamus.

Together with the paraventricular nucleus (PVN), the dorsomedial nucleus of the hypothalamus (DMH) acts as one of the hypothalamic centers that integrate autonomic and central information. The DMH in the rat brain has extensive intrahypothalamic connections and is implicated in a wide variety of functions. Up until now, no knowledge has been available to indicate that the human DMH might have functions similar to those of the rat DMH. In the present study, intrahypothalamic efferent projections of the human DMH were revealed by a recently developed in vitro postmortem tracing method. It was found that the most densely innervated areas are the PVN, the ventromedial nucleus of the hypothalamus, and the area below the PVN. Other significant terminal fields include the periventricular nucleus, the lateral hypothalamic area, and the medial part of the anteroventral hypothalamic area. Scarce fibers project to the suprachiasmatic nucleus, infundibular nucleus, posterior hypothalamic nucleus, and posterior part of the bed nucleus of the stria terminals. The projections of the ventral and dorsal part of the DMH show some differences. The dorsal part of the DMH has denser projections to the dorsal part of the PVN than to the ventral part of the PVN. In contrast, the ventral part of the DMH has denser projections to the ventral part of the PVN. Labeled fibers in the PVN from ventral and dorsal DMH appear to run near many vasopressin and oxytocin neurons of different sizes, and also near some corticotropin- releasing hormone neurons, suggesting that the DMH neurons may directly affect the functioning of these PVN neurons. In many aspects, the observed projections of the human DMH resemble those of the rat, indicating that the organization of DMH intrahypothalamic projections of human is similar to that of rat. The functional significance of DMH intrahypothalamic connections is discussed.

Brain Mapping↗

Tyrosine hydroxylase-expressing and/or aromatic L-amino acid decarboxylase-expressing neurons in the mediobasal hypothalamus of perinatal rats: differentiation and sexual dimorphism.

In this quantitative and semiquantitative immunocytochemical study, the authors evaluated the differentiation of neurons expressing tyrosine hydroxylase (TH) and/or aromatic L-amino acid decarboxylase (AADC) in the mediobasal hypothalamus (MBH) of male and female rats on embryonic day 18 (E18), E20, and postnatal day 9 (P9). Four neuronal populations were distinguished according to either enzyme expression or neuron location. The earliest and most prominent first population was represented by TH-immunoreactive (IR)/AADC-immunonegative (IN) neurons that were detected initially at E18 and always were located in the ventrolateral region of the MBH. The second population of TH-IN/AADC-IR neurons was observed first at E20 and, after that time, was distributed dorsomedially. The third minor population of TH-IR/AADC-IR neurons initially was detected at E20 and was located dorsomedially. The fourth population was represented by TH-IR/AADC-IN neurons that were distributed in the dorsomedial region at any studied age. The numbers of TH-IR and AADC-IR neurons increased from their initial detection at E18 and E20 until P9. The area of TH-IR and AADC-IR neurons also increased from E18 to E20 and from E20 to P9, respectively. Both TH-IR and AADC-IR neurons showed sex differences in the neuron number, size, and optic density (OD). The numbers of TH-IR neurons in males exceeded those of females at E20 and at P9, although, at P9, sexual dimorphism was a characteristic only of the ventrolateral population. The area and OD of TH-IR neurons from females exceeded those from males in the entire mediobasal hypothalamus (MBH) at E18 and E20 but only in its dorsomedial region at P9. Sexual dimorphism also was an attribute of AADC-IR neurons at E20 and P9. Their number, size, and OD were significantly higher in females than in males. Thus, the MBH of perinatal rats contained two major populations of TH-IR/AADC-IN or TH-IN-AADC-IR neurons and a minor population of TH-IR/AADC-IR neurons. The differentiating neurons expressing either enzyme showed sexual dimorphism.

Age Factors↗

Receptors and neural effects of oxytocin in the rodent hypothalamus and preoptic region.

Vasopressin and oxytocin are produced in and secreted from not only hypothalamo-hypophysial neurons which shed their products into the circulation to act as hormones or releasing factors, but also from neurons whose axons form tracts which remain within the central nervous system. Using tritiated or radioiodinated ligands, binding sites for vasopressin and for oxytocin have been detected by in vitro autoradiography. In the rat hypothalamus binding sites for vasopressin are present in the suprachiasmatic, sigmoid and arcuate nuclei, and oxytocin receptors in the area of the ventromedial nucleus. Electrophysiological evidence obtained using single cell recordings in slices suggests that oxytocin-binding sites present in the ventromedial hypothalamus and in the bed nucleus of the stria terminalis mostly represent functional, neuronal receptors. The expression of these receptors (but not of the vasopressin receptors) depends on gonadal steroid hormones, as does that of uterine and mammary gland oxytocin receptors. Modifications of the hormonal status associated with, for example, puberty and lactation cause 'up-regulation' of central and peripheral oxytocin receptors. The central administration of oxytocin facilitates (and the administration of oxytocin agonists inhibits) maternal behaviour and the milk ejection reflex, therefore the hormonal and neural actions of oxytocin appear to be complementary in ensuring the birth and development of the offspring.

Animals↗

Glucose hypometabolism of hypothalamus and thalamus in narcolepsy.

It has been hypothesized that hypothalamus is involved in narcolepsy. The relative difference between cerebral glucose metabolism of 24 narcoleptic patients and 24 normal controls was studied using 18F-fluorodeoxy glucose positron emission tomography. Patients with narcolepsy showed significantly reduced cerebral glucose metabolism in bilateral rectal and subcallosal gyri, the medial convexity of right superior frontal gyrus, bilateral precuneus, right inferior parietal lobule, and in left supramarginal gyrus (uncorrected p < 0.001). Bilateral posterior hypothalami and mediodorsal thalamic nuclei showed hypometabolism with significance at the level of corrected p < 0.05, with small volume correction. This study showed cerebral glucose hypometabolism of the hypothalamus-thalamus-orbitofrontal pathways in the narcoleptic brain.

Adolescent↗

The hypothalamus in Parkinson disease.

The hypothalamus was systematically examined in 30 patients with pathologically documented idiopathic parkinsonism. Using Lewy body formation as a marker for nerve cell degeneration, we observed abnormalities in every hypothalamus examined. Of the thirteen hypothalamic nuclei that could be individually identified, none were exempt from Lewy body degeneration. The tuberomamillary nucleus and the lateral and posterior hypothalamic nuclei demonstrated the highest average Lewy body counts (16, 9, and 3, respectively); they were also the most frequently involved nuclei. These findings may aid in interpretation of the autonomic and endocrine abnormalities in patients with Parkinson disease.

Aged↗

AMPA glutamate receptor subunits in the guinea pig hypothalamus: distribution and colocalization with progesterone receptor.

Excitatory amino acids (EAAs), particularly glutamate, have been implicated in the control of luteinizing hormone (LH) secretion through facilitation of gonadotropin-releasing hormone release. The effects of EAAs are mediated by means of ionotropic glutamate receptors, which are divided into N-methyl-D-aspartate (NMDA) and non-NMDA (kainate and AMPA) subtypes. Moreover, ovarian steroids are responsible for inducing the preovulatory surge of LH and are involved in the actions of EAAs on LH release. Progesterone is directly involved in the potentiating effect of ovarian steroids on the stimulating effect of AMPA neurotransmission on gonadotropin secretion. To broaden our understanding of the role of hypothalamic AMPA receptors in the steroid-induced LH surge, we determined the cellular localization of AMPA receptors in the hypothalamus of guinea pigs by using antibodies that recognize the GluR1, GluR2, GluR2/3, or GluR4 subunits, and then we examined the neuroanatomic relationships between these receptors and the progesterone receptor (PR). Different patterns of immunostaining within the preoptic area and hypothalamus were evident with the antibodies to the four subunits with marked contrasts between moderate staining for GluR1, intensely stained structures for GluR2 and GluR2/3, and little specific staining for GluR4. Immunoreactive (IR) neurons were visualized in many regions, including the two regions known to contain a dense population of estradiol-induced PR-IR cells: the preoptic periventricular and ventrolateral hypothalamic nuclei. Approximately 60% of GluR1-IR and 39% of GluR2-IR cells in the preoptic region possessed PR, whereas 46% of GluR1-IR and 54% of GluR2-IR cells in the ventrolateral nucleus expressed PR. These neuroanatomic results suggest that the coordinated actions of progesterone and glutamatergic inputs on mammalian reproductive functions are integrated at the cellular level.

Animals↗

Stereologic analysis of estrogen receptor alpha (ER alpha) expression in rat hypothalamus and its regulation by aging and estrogen.

The estrogen receptor alpha (ERalpha) in the hypothalamus plays important roles in the regulation of reproductive development, physiology, and behavior. However, the expression of the ERalpha may change during aging or in response to varying estrogen levels. The present study measured changes in the numbers of ERalpha-expressing cells in specific hypothalamic and preoptic nuclei of ovariectomized female Sprague-Dawley rats at three ages (young [3-4 months], middle-aged [10-12 months], or old [24-26 months]) and with or without estrogen replacement. Numbers of ERalpha-immunoreactive neurons were quantified in four regions relevant to reproductive function: the anteroventral periventricular nucleus (AVPV), medial preoptic nucleus (MPN), arcuate nucleus (ARH), and ventromedial nucleus (VMN), using an unbiased stereologic approach. In the AVPV and VMN, significant age-related increases in the numbers of ERalpha-expressing cells from the middle-aged to the old group were detected, and no differences were observed in the MPN and ARH, indicating that ERalpha neuron number is maintained or even elevated during aging. No significant effects of estrogen on ERalpha cell number were detected in any of the four regions studied. Therefore, ERalpha cell number in the rat hypothalamus and preoptic area changes with aging in a region-specific manner.

Aging↗

Anatomic relationships between aromatase and androgen receptor mRNA expression in the hypothalamus and amygdala of adult male cynomolgus monkeys.

This study mapped the regional locations of cells expressing cytochrome P450 aromatase (P450AROM) and androgen receptor (AR) mRNAs in the adult male macaque hypothalamus and amygdala by in situ hybridization histochemistry using monkey-specific cRNA probes. High densities of P450AROM and AR mRNA-containing neurons were observed in discrete hypothalamic areas involved in the regulation of gonadotropin secretion and reproductive behavior. P450AROM mRNA-containing neurons were most abundant in the medial preoptic nucleus, bed nucleus of the stria terminalis, and anterior hypothalamic area, whereas AR mRNA-containing neurons were most numerous in the ventromedial nucleus, arcuate nucleus, and tuberomamillary nucleus. Moderate to heavily labeled P450AROM mRNA-containing cells were present in the cortical and medial amygdaloid nuclei, which are known to have strong reciprocal inputs with the hypothalamus. Heavily labeled P450AROM mRNA-containing cells were found in the accessory basal amygdala nucleus, which projects to the cingulate cortex and hippocampus, areas that are important in the expression of emotional behaviors and memory processing. In contrast to P450AROM, the highest density of AR mRNA labeling in the temporal lobe was associated with the cortical amygdaloid nucleus and the pyramidal cells of the hippocampus. All areas that contained P450AROM mRNA-expressing cells also contained AR mRNA-expressing cells, but there were areas in which AR mRNA was expressed but not P450AROM mRNA. The apparent relative differences in the expression of P450AROM and AR mRNA-containing neurons within the monkey brain suggests that T acts through different signaling pathways in specific brain areas or within different cells from the same region.

Amygdala↗

Ontogeny of the projections from the anteroventral periventricular nucleus of the hypothalamus in the female rat.

Neurons in the anteroventral periventricular nucleus of the hypothalamus (AVPV) mediate a variety of autonomic functions. In adults they primarily innervate neuroendocrine nuclei in the periventricular zone of the hypothalamus, including the paraventricular and arcuate nuclei (PVH, ARH). Ascending projections from the AVPV also provide inputs to the ventrolateral septum (LSv) and the principal division of the bed nuclei of the stria terminalis (BSTp). Consistent with a role in regulating preovulatory luteinizing hormone secretion, rostral projections from the AVPV contact gonadotropin-releasing hormone (GnRH) neurons surrounding the vascular organ of the lamina terminalis (OVLT). To study the development of these pathways, we placed implants of the lipophilic tracers DiI and CMDiI into the AVPV of female rats ranging in age from embryonic day 19 (E19) through adulthood. The earliest projections targeted a population of GnRH neurons, with apparent contacts from labeled fibers observed as early as E19. These connections appeared to be fully developed before birth, as similar numbers of appositions from AVPV projections onto the GnRH-immunoreactive cells were observed at all ages examined. Caudal projections were delayed relative to projections to the OVLT. Labeled AVPV fibers reached the PVH during the first postnatal week, and fibers targeting the BSTp and LSv were not observed until the second and third postnatal weeks, respectively. Labeled AVPV fibers were not seen in the ARH of animals at any age. Our results demonstrate that projections from the AVPV develop with both spatial and temporal specificity, innervating each target with a unique developmental profile.

Aging↗

Catecholamine distribution in feline hypothalamus.

Catecholamine distribution was examined in cat hypothalamus using the histochemical fluorescence technique of Falck and Hillarp. The heaviest accumulations of catecholamine-containing varicosities were seen within the: anterior periventricular nucleus; dorsal hypothalamic area; bed nucleus of the inferior thalamic peduncle; doral component of the paraventricular nucleus; dorsomedial nucleus; infundibular nucleus; bed nucleus of the stria terminalis-medial division; and supraoptic nucelus. Catecholaminergic perikarya were observed within periventricular, dorsal, and caudal hypothalamic areas as well as within the supramamillary nucleus and caudal diencephalon. Catecholamine distribution in cat hypothalamus possesses both similarities and dissimilarities in relation to distributions reported in other mammals.

Animals↗

Taste pathways to hypothalamus and amygdala.

The projections of a third order gustatory relay in the dorsal pons of rats have been traced using tritiated proline autoradiography and antidromic activation of pontine neurons from electrodes in the thalamus and amygdala. Labelled axons collect in the central tegmental tract and ascend to the thalamic taste area in the medial extension of the ventrobasal complex. The majority of the fibers remain ipsilateral, but a few cross in the rostral pons and midbrain. The largest crossing occurs at the level of the thalamic termination. Many fascicles of fibers continue rostrally by passing beneath the thalamic taste area, piercing the medial lemniscus, and spreading out along the dorsomedial corner of the internal capsule (IC). The terminal field at this level caps IC from the subthalamic nucleus down into the far-lateral hypothalamus. Labelled axons grandually penetrate through the internal capsule, and ramify throughout the underlying substantia innominata. This terminal zone extends laterally into the rostral end of the central nucleus of the amygdala, which is densely labelled to its caudal exremity. At the caudal end of the amygdala labelled fibers are visible in one component of the stria terminalis. These fibers can be followed over the dorsal thalamus into a smaller, but equally dense terminal area in the dorsolateral bed nucleus of the stria terminalis. The electrophysiological data demonstrate that pontine gustatory units can be antidromically activated by electrodes located in or near the central nucleus of the amygdala. Since many of the same units can also be driven from the thalamic taste area, at least some of the axons traced autoradiographically probably convey gustatory information to the hypothalamus and amygdala.

Amygdala↗