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Evidence of a direct action of angiotensin II on neurones in the septum and in the medial preoptic area.

Angiotensin II (AII) was microiontophoretically applied on neurones located in the septum and the medial preoptic area (MPOA). All the septal neurones sensitive to AII (15/37) responded by an inhibition to the peptide application. Of 44 units tested in the MPOA 21 cells (48%) were sensitive to AII and responded either by an increase (11/21) or decrease (10/21) in their firing. The specificity of these responses were ascertained by simultaneous application of the antagonist Sar-Ile-Angiotensin II. These data suggest that Angiotensin II acts directly on neurones of the septum and medial preoptic area, structures implicated in the control of drinking behaviour.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Oxytocin but not vasopressin facilitates social recognition following injection into the medial preoptic area of the rat brain.

Social recognition of juvenile rats by adult male residents has been shown to be modulated by peripheral administration of neurohypophyseal hormones vasopressin and oxytocin. In the present study, the effects of these peptides on social recognition were investigated after local injection into the medial preoptic area of the hypothalamus. It was found that oxytocin given in a wide range of doses (0.3-1000 pg) facilitated social recognition. This effect was not blocked by pretreatment with oxytocin receptor antagonist desGly(NH2)9-d(CH2)5[Tyr(Me)2Thr4]OVT. Oxytocin injected into the septum in doses of 0.03-3 pg was not effective. Administration of vasopressin (100 or 1000 pg), [pGlu4,Cyt6]AVP-(4-8) (200 pg) or [pGlu4,Cyt6]AVP-(4-9) (200 pg) into the medial preoptic area did not influence social recognition. It is concluded that the medial preoptic area is a sensitive brain site for the oxytocin-induced facilitation of social recognition in rats.

Angiotensin Receptor Antagonists↗

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.

Animals↗

Fos expression in luteinizing hormone-releasing hormone neurons of guinea pigs, with knife cuts separating the preoptic area and the hypothalamus, demonstrating luteinizing hormone surges.

LHRH neurons in guinea pigs, as in primates and other non-rodent species, are broadly distributed in the basal forebrain. In this study, knife cuts were made in the anterior hypothalamus, effectively separating more caudally positioned hypothalamic LHRH neurons from those in rostral preoptic areas. Guinea pigs with knife cuts displayed an LH surge in response to steroid administration. There was no significant difference in the number of LHRH neurons that expressed Fos in conjunction with an LH surge, although fewer total LHRH neurons were detected in the forebrain of knife-cut versus sham-cut animals. Knife-cut animals displayed a larger percentage of LHRH/Fos neurons in one region of the caudal hypothalamus than sham-cut animals. The area and perimeter of the LHRH reaction product within the cytoplasm of LHRH/Fos neurons were smaller than those of single-labeled LHRH neurons in sham-cut animals and in the caudal hypothalamus, but not the rostral preoptic area, of knife-cut animals. We conclude that caudal hypothalamic LHRH neurons separated from rostral preoptic regions are capable of sustaining an LH surge in guinea pigs. This finding is important, as LHRH neurons are present in the caudal hypothalamus, as well as in preoptic areas, of a large number of mammalian species, including humans.

Animals↗

Synaptogenesis in the neonatal preoptic area grafted into the aged brain.

The medial preoptic area (POA) of newborn female rats was transplanted into the third ventricle of young adult (2 months of age) and aged (27 months of age) female rats. The grafted POA tissues were examined ultrastructurally 2 months after transplantation. The mean numbers of axodendritic shaft and spine synapses in the POA transplants in both young adult and aged female rats were much greater than those in the medial POA of newborn female rats. These results suggest that the neuronal substrates in the medial POA grafts develop well in the brain of the aged female rats.

Aging↗

Why the medial preoptic area is important for sleep regulation.

The medial preoptic area (mPOA) is one of the many areas in the brain that control sleep. Apart from sleep, the mPOA is important for the regulation of body temperature, and other important body functions aimed at energy homeostasis. In sleep regulation, the major function of this area is to maintain sleep. Though the mPOA controls sleep and body temperature through independent neuronal circuits, it is essential for organising the sleep architecture, as per the thermoregulatory requirement. The functional integrity of the mPOA may be essential for the regulation of energy homeostasis, in response to alterations in the ambient temperature, heat producing physical activity and sleep-wakefulness. Thus, the mPOA forms part of the brain that integrates regulations aimed at preservation of self. The mPOA is important for maintaining the "set point" for not only body temperature, but it is also important for maintaining the "set point" for several physiological parameters including sleep-wakefulness.

Animals↗

Stimulation of cholinergic receptors in the medial preoptic area affects sleep and cortical temperature.

The medial preoptic area (MPA), a cholinoceptive brain area devoid of cholinergic cells, plays an important role in the regulation of different physiological functions, particularly sleep control and thermoregulation. To investigate the effects of the stimulation of cholinergic receptors in this area on sleep and cortical temperature (Tcort), carbachol (a mixed cholinergic agonist) was directly microinjected into the MPA of freely moving rats. Carbachol (0.25 and 0.5 microgram, corresponding to 1.37 and 2.74 nmol) microinjection induced an increase in wakefulness and an inhibition of both slow wave and desynchronized sleep phases. The temperature of the cerebral cortex was reduced in comparison with control conditions (saline microinjection). Sterile needle insertion and saline microinjections induced a significant increase in Tcort, but no changes in the sleep-wake cycle compared with the handling of the animal. The results suggest that 1) carbachol microinjection into the MPA can activate an arousal-generating system and affect thermoregulatory mechanisms, and 2) sleep and temperature responses may be dissociated.

Animals↗

Sex differences in dentritic patterns in hamster preoptic area.

Sexual dimorphism is described in the dentritic field pattern of Golgi-stained neurons from the dorsomedial preoptic area of adult golden hamsters (Mesocricetus auratus). Data were obtained through a mathematical reconstruction of dentritic densities of neurons sampled from this area in males and females. Males tended to have a central concentration, while females showed an irregular dendritic density distribution with concentrations dorsolateral, ventral and medial to the area of highest dentriic density in the males. These results suggest sex differences in the afferent inputs to neurons in the dorsomedial preoptic area which may be related to functional sexual dimorphism in physiology and behavior.

Animals↗

Effects of postweaning rearing condition on recovery of copulatory behavior from lesions of the medial preoptic area in rats.

Bilateral lesions of the medial preoptic area (MPOA)-anterior hypothalamus of adult male rats markedly disrupt male copulatory behavior. In contrast, more group--reared then isolated male rats receiving bilateral MPOA lesions as juveniles copulated to ejaculation as adults. The present experiment was designed to analyze the role of rearing condition in promoting copulatory recovery from MPOA lesions in juvenile male rats. Juvenile male rats were given bilateral MPOA lesions or a sham operation and reared in isolation without handling, in isolation with daily handling, across a perforated Plexiglas divider from a male peer, or together with a male peer (social). Socially reared and handled males, but not isolated and divided males, with MPOA lesions showed evidence of copulatory recovery (combined socially reared and handled males vs combined isolated and divided males). These results support previous findings that postweaning rearing condition can affect copulatory recovery following juvenile MPOA lesions, but indicate that play experiences involving physical contact with peers are not necessary for such recovery to occur.

Animals↗

Neurotropic effects of estrogen on the neonatal preoptic area grafted into the adult rat brain.

The preoptic area (POA) or cerebral cortex taken from newborn female rats were transplanted into the third ventricle of ovariectomized adult rats. From the day of transplantation, estradiol-17 beta in a silastic capsule was implanted subcutaneously into host animals for 4 weeks. The POA or cerebral cortex transplants were examined at light- and electron-microscopic levels 4 weeks after transplantation. All of the POA or cortical grafts showed an appearance similar to normal neural tissue. Estrogen exposure for 4 weeks via the host induced a significant increase in the volume of the POA grafts. The neuronal population of the POA grafts exposed to estrogen was not significantly different from that of the POA grafts without estrogen treatment. However, the number of axodendritic shaft and spine synapses of the POA grafts exposed to estrogen was significantly greater than that of the POA grafts without estrogen treatment. In contrast, there was no significant difference in the volume of the cortical tissues transplanted into the brain between the control and estrogen-treated groups. These results suggest that estrogen has a stimulatory effect on the development of neuronal substrates in the intraventricular POA graft, increasing its volume and synaptic population.

Animals↗

Neonatal testosterone modifies LH secretion in the adult female rat by altering the opioid-noradrenergic interaction in the medial preoptic area.

Noradrenergic-opioid interaction in the medial preoptic area (MPOA) was examined in ovariectomised adult rats which were oestrogen-treated and had been injected neonatally with either testosterone propionate (TP) or vehicle (oil). The first experiment involved electrical stimulation of the ventral noradrenergic tract (VNAT) in anaesthetised rats. Blood samples were collected before and after the stimulation to determine plasma levels of luteinising hormone (LH). Approximately half of the animals received naloxone i.v. 15 min before the onset of stimulation. In all groups, stimulation of VNAT elicited a significant increase in plasma LH concentration. However, pretreatment with naloxone in androgenised rats, but not in oil-treated animals, almost doubled the LH increment due to stimulation. Naloxone had no effect on plasma LH concentrations in unstimulated control rats. In the second experiment hypothalamic slices containing the MPOA were preincubated with [3H]noradrenaline [( 3H]NA) and then subjected to electrical field stimulation under the conditions of (a) no drug added and (b, c) morphine superfusion without and with naloxone. The opioid agonist morphine significantly reduced the net release of [3H]NA in normal and TP-treated female rats. Addition of equimolar naloxone reversed this effect in normal females, whereas in the androgenised group it not only reversed this effect but elicited a significant increase in [3H]NA release. From these data we conclude that (1) neonatal testosterone treatment alters noradrenergic-opioid interaction regulating LH secretion in adult females and (2) the site of this change may be the presynaptic opioid input to the noradrenergic terminals in the MPOA.

Animals↗

Ontogeny of the expression of some catecholamine synthesising enzymes in the female porcine preoptic area.

Ontogeny of the catecholaminergic system of the preoptic area (PA) was studied in various animal species including mice, rats, cats and lower vertebrates. Until now, there has been no data about development of catecholaminergic structures in the porcine PA. To study this problem, hypothalami from six groups of animals were collected. Three groups of foetuses (70, 84 and 112 days old) and three groups of female pigs (1 day, 10 weeks and 7-8 months old) were used. Nerve structures immunoreactive for the studied substances: tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DbetaH) and phenylethanoloamine-N-metylthransferase (PNMT) were observed in different periods. In PA, TH-IR (immunoreactive) structures appeared before 70th day of foetal life, DbetaH-IR between 70th and 84th day of foetal live and PNMT-IR only in 10-week old and adult animals. In the PA of 70-day old foetuses, single smooth and varicose nerve fibres immunoreactive only to TH were found. In PA of 84-day old foetuses, additionally, single nerve cell bodies immunoreactive to TH were shown and some of them also contained immunoreactivity to DbetaH. In PA of 1-day old piglets, moderate numbers of nerve fibres immunoreactive to TH and only single TH/DbetaH-IR nerve terminals were observed. TH-IR nerve cell bodies were also moderate in number and many of them contained simultaneously immunoreactivity to DbetaH. In PA of 10-week old pigs, a moderate number of immunopositive nerve fibres was observed. They contained mainly TH, but part of them stained also for TH/DbetaH. Only very few nerve fibres containing exclusively DbetaH were found. These nerve terminals were observed in a close vicinity of blood vessels. In PA, moderate numbers of TH-IR nerve cell bodies were found, some of them contained also immunoreactivity to DH but never to PNMT. Perikarya containing PNMT were TH-negative. In the PA of sexually mature sows, additional, single, large nerve cell bodies (about 35 microm in a diameter) containing TH only were found. In many cases, TH- and DbetaH-IR "basket-like" structures surrounding nerve cell bodies were seen, suggesting an influence of those fibres on the neuronal activity.

Animals↗

Sex differences in estrogen receptor and progestin receptor induction in the guinea pig hypothalamus and preoptic area.

Quantitative in vitro autoradiography was used to determine if regional sex differences in estrogen receptor (ER) content and/or estrogen responsiveness, as indicated by an increase in progestin receptor (PR), are present in the adult guinea pig brain. Adult male and female guinea pigs were gonadectomized 1 week before subcutaneous injection of 25 micrograms estradiol benzoate (EB)/kg body wt or the sesame oil vehicle. Animals were killed by decapitation 44 h after injection. Unoccupied PRs, and unoccupied and occupied ERs, were measured in discrete brain regions by quantitative in vitro autoradiography using [3H]R5020 and [3H]estradiol as ligands, respectively. In vehicle-injected controls, a higher level of ER was found in the arcuate nucleus (ARC), dorsal medial nucleus (DMN) and ventrolateral nucleus (VLN) of females as compared to males. At 44 h after EB injection, 32-55% of the ERs were occupied; however, EB treatment caused a marked down-regulation of total receptor (calculated as occupied+ unoccupied receptor) in most of the brain regions examined, including the periventricular preoptic area (PVP), medial preoptic area (MPO), bed nucleus of the stria terminalis, paraventricular nucleus, ARC, ventrolateral hypothalamus (VLH), VLN, and DMN. In EB-treated animals, PR binding was detectable in the PVP, MPO, ARC, VLH, and VLN, with higher levels of binding observed in the PVP, MPO, and VLN of the female as compared to the male. No PR binding was observed in oil-injected control animals. These results demonstrate region-specific sex differences in ER as well as estrogen-induced regulation of progestin and ERs in the guinea pig brain. The discordance between the regional distributions of sex differences in ER and estrogen-induced PR implies that sex differences in ER and estrogen-induced PR implies that sex differences in estrogen response may not be clearly linked to a sex difference in receptor number. Instead, sex differences in response may involve differences in receptor number within specific subpopulations of estrogen target cells or may involve differences in ER dynamics.

Animals↗

Cardiovascular effects produced by R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin in the preoptic area of conscious rats.

Experiments were designed to test the hypothesis that activation of forebrain 5-HT1A receptors elicits cardiovascular responses. The microinjection of R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin [(+)-8-OH-DPAT], a selective 5-HT1A receptor agonist, in the preoptic area of conscious rats increased blood pressure and heart rate at doses of 0.2-20 nmol; lower doses (0.002 and 0.02 nmol) were ineffective. The concomitant administration of methiothepin, a non-selective 5-HT receptor antagonist, into the preoptic area attenuated the responses. In addition, the tachycardia elicited by (+)-8-OH-DPAT was abolished by the peripheral beta-adrenoceptor antagonist sotalol, but not by atropine methyl nitrate. Finally, the tachycardia, but not the hypertension, was also produced by (+)-8-OH-DPAT in urethane-anesthetized rats. These results suggest that activation of 5-HT1A receptors in the preoptic area or an adjacent region of the forebrain produces: (1) an increase in heart rate consistent with sympathoadrenal activation; and (2) an increase in blood pressure which might be the result of sympathoexcitation or secondary to behavioral arousal.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Fos expression within regions of the preoptic area, hypothalamus and brainstem during pregnancy and parturition.

Vaginocervical stimulation, that occurs during mating or with the birth of pups, is believed to induce specific sexual and maternal behaviours in the rat as well as stimulating a number of neuroendocrine responses including the secretion of oxytocin, prolactin and luteinizing hormone. Since the medial preoptic area has been implicated in the induction of maternal behaviour, the expression of the immediate-early gene product Fos was compared between non-pregnant, late pregnant and parturient rats. Although no difference was detected in the number of Fos-positive neuronal profiles in the preoptic area of non-pregnant and late-pregnant rats, a large increase was observed in the medial preoptic nucleus and the anteroventral periventricular region, as well as in the hypothalamic supraoptic nucleus, of parturient rats. Double labelling for Fos and tyrosine hydroxylase immunoreactivity in the brainstem of parturient rats showed the activation of catecholaminergic neurons in both the nucleus of the tractus solitarius and in the ventrolateral medulla that may form part of the afferent pathway from the uterus and cervix to the preoptic area and hypothalamus.

Afferent Pathways↗

GABAergic and catecholaminergic innervation of mediobasal hypothalamic beta-endorphin cells projecting to the medial preoptic area.

In the absence of cellular estrogen receptors or proven direct estrogen action in the rat, it is assumed that estrogen indirectly regulates the secretory activity of the preoptic area luteinizing hormone-releasing hormone-producing cells. We have previously shown that pro-opiomelanocortin neurons in the arcuate nucleus of the rat send axons rostrally to connect with luteinizing hormone-releasing hormone neurons of the preoptic area. An experiment combining retrograde tracing and double-immunostaining was used to test the hypothesis that rat GABAergic and/or catecholaminergic neurons can influence luteinizing hormone-releasing hormone-producing cells via mediobasal hypothalamic beta-endorphin neurons. The retrograde tracer horseradish peroxidase was injected into the medial preoptic area; two days later, arcuate nucleus Vibratome sections were double-immunostained for beta-endorphin and glutamate decarboxylase or tyrosine hydroxylase. Light and electron microscopic analysis of these triple-labeled sections demonstrated that a population of beta-endorphin-immunoreactive neurons concentrated in the ventromedial arcuate nucleus contain retrogradely transported horseradish peroxidase granules and form synaptic contacts with glutamate decarboxylase- and tyrosine hydroxylase-immunoreactive axon terminals. The present data suggest that arcuate nucleus GABA and catecholamine fibers may influence luteinizing hormone-releasing hormone-containing neurons via projective pro-opiomelanocortin cells.

Animals↗

Osmosensitive neurons in the rat's preoptic area: medial-lateral comparison.

For the first time, brain-recording data were brought to bear directly on the question of a critical osmosensitive zone in the lateral preoptic area as specifically delimited in the rat by Blass and Epstein, and in the rabbit by Peck and Novin. Our data clearly showed that this critical zone in the lateral preoptic area of the rat contains cells that are osmosensitive. Simultaneous recording from cell populations (a) inside the critical zone and (b) in a zone medial to it showed that the net acceleratory response to challenge for the former was much greater than it was for the latter. These findings constitute new evidence for the critical importance of the lateral preoptic area in cellular dehydration thirst.

Animals↗

Fos expression in rat pontine tegmental neurons following activation of the medial preoptic area.

Fos immunohistochemistry was used to map the distribution of pontine neurons excited by activation of the medial preoptic area (MPO). Although we have previously shown that Barrington's nucleus receives a very dense focal input from the MPO, electrical stimulation of the preoptic area unexpectedly induced very little Fos expression in Barrington's neurons. These results suggest that the MPO-->Barrington's projection utilizes a transmitter(s) that does not involve transduction of the Fos protein; alternatively, MPO afferents to Barrington's nucleus may be inhibitory in nature. As Barrington's nucleus plays a critical role in micturition, MPO projections to Barrington's nucleus may regulate voiding reflexes during sexual behavior. Interestingly, while the locus coeruleus (LC) proper receives only a sparse projection from the MPO, extensive Fos expression was present in LC. The finding of Fos immunoreactive LC neurons suggests that the excitatory influence of MPO may regulate LC neuronal activity and NE release during reproductive behaviors.

Animals↗