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At least 19 recordsLinked to original sources
PubMed1997

Neonatal treatment with tamoxifen causes immediate alterations of the sexually dimorphic nucleus of the preoptic area and medial preoptic area in male rats.

Tamoxifen is an antiestrogen widely used for the treatment of breast cancer. Current evolutions in preventive strategies to include healthy premenopausal women warrant the study of its developmental toxicity. Perinatal treatment of male rodents with tamoxifen caused reproductive tract lesions and sexual behavior deficits similar to those induced by diethylstilbestrol (DES). Those abnormalities could originate, at least in part, from lesions of the hypothalamic-pituitary axis. The initial alterations caused by tamoxifen in the hypothalamic medial preoptic area (MPOA) and sexually dimorphic nucleus of the preoptic area (SDN-POA) were studied in 6-day-old male rat pups treated with 100 micrograms tamoxifen (group 1), 1 microgram DES (group 2) or vehicle (group 3) from PN1 to 5. In situ hybridization was performed to analyze the expression of the GAP-43 gene, a marker of neuronal differentiation, and morphometry was used to study the neuronal density in the SDN-POA and MPOA and the volume and number of neurons in the SDN-POA. Tamoxifen reduced severely the volume and neuron numbers in the SDN-POA (46.1% and 47.8% of controls, respectively). The neuronal density of the MPOA was not modified. GAP-43 gene expression was decreased as demonstrated by a greater percentage of unlabeled neurons (grade 0) mirrored by a lesser percentage of intensely labeled ones (grade 2) in the SDN-POA and MPOA. In contrast to the effects of the antiestrogen, DES did not affect the above endpoints. These data indicated that developmental exposure of male rat pups to tamoxifen-induced immediate neuronal loss in one and altered differentiation in two hypothalamic areas crucial to reproduction. How those initial alterations contribute to the pathogenesis of the reproductive disorders observed in the adult male needs further investigation.

Animals↗
PubMed1996

Estrogen uncouples noradrenergic activation of Fos expression in the female rat preoptic area.

The preoptic area of the rat brain is a site at which gonadal steroids act to regulate sexual behaviour and gonadotrophin secretion. The expression of the immediate-early gene product, Fos, in the preoptic area was investigated in conscious ovariectomised, vehicle and estrogen-treated animals which had received an intracerebroventricular (i.c.v.) infusion of noradrenaline, and also in anaesthetised proestrous and ovariectomised rats following electrical stimulation of the brainstem A1 or A2 noradrenergic cell groups. In ovariectomised oil-treated rats, a third ventricular infusion of noradrenaline (45 micrograms) resulted in a significant (P < 0.05) increase in the numbers of Fos-immunoreactive cell nuclei throughout the preoptic area, compared to vehicle controls. In contrast, Fos expression in animals which had received estrogen replacement showed no change in response to i.c.v. noradrenaline compared with saline-treated controls. In anaesthetised, ovariectomised animals electrical stimulation of the A1 cell group resulted in a significant increase (P < 0.05) in Fos-like immunoreactivity compared with sham controls, specifically within the ventral preoptic area whilst stimulation of the A2 cell group had no significant effect. In anaesthetised, proestrous rats receiving electrical stimulation no significant changes in Fos-like immunoreactivity were detected within the preoptic area after either A1 or A2 stimulation compared with paired controls. These results show that noradrenaline-induced Fos expression in the preoptic area is dependent on estrogen status and suggest that the estrogenic regulation of reproductive functions may thus involve altered responses to noradrenaline in sub-populations of preoptic neurones.

Animals↗
PubMed2002

Sexual differentiation of astrocyte morphology in the developing rat preoptic area.

The preoptic area is an important brain region controlling sex-typic behaviour and physiology, and astrocytes of this region are responsive to steroids perinatally. Utilizing glial fibrillary acidic protein immunocytochemistry, the morphology of astrocytes in the preoptic area of male and female rat pups was examined on the day of birth and on postnatal day 3. As early as the day of birth, astrocytes of the male preoptic area exhibit both significantly greater primary process length and number of primary processes, and these differences remain at postnatal day 3. Application of exogenous steroid to females suggested that gonadal steroids, in particular oestradiol, mediate the sex difference. Pups received 100 micro g of steroid on the day of birth and again on postnatal day 1, and astrocyte morphology was assessed on postnatal day 3. Both oestradiol and testosterone induced significant changes in process length and number compared to vehicle-treated controls. Astrocytes of oestradiol-treated females did not differ on PN3 from those of PN3-untreated males. Exposure to the nonaromatizable steroid, dihydrotestosterone, had no effect on any attribute of astrocyte morphology. This suggests the effects induced by testosterone are mediated by oestradiol following local aromatization of the steroid, and not through direct activation of the androgen receptor. Astrocytes are important in synapse formation and efficacy, and we hypothesize a role for astrocyte complexity and differentiation in the establishment of synaptic patterning.

Aging↗
PubMed1996

Concurrent androgenic stimulation of the ventral tegmental area and medial preoptic area: synergistic effects on male-typical reproductive behaviors in house mice.

Cannulae containing testosterone proprionate (T) were bilaterally implanted into the medial preoptic area (MPO), the ventral tegmental area (VTA), or both areas concurrently (MPO/VTA) of castrated male house mice. A fourth group of castrates in which the intracranial implants missed their targets (MIMP) served as controls. In addition, other castrates were implanted subcutaneously with empty silastic capsules (BSIL) or silastic capsules containing T (TSIL). All subjects were examined for the following male-typical behaviors: mounting, attraction to female urine, ultrasonic mating vocalizations and urinary scent marking. In addition, the males were tested for activity levels to insure that they were not motorically impaired. In general, TSIL implants restored all male-typical behaviors to normal levels, whereas BSIL and MIMP implants were generally ineffective. Similar to previous findings, MPO implants alone completely restored ultrasonic vocalizations, partially restored urine marking, and had little or no effect upon mounting or urine preference. In contrast, VTA implants alone were ineffective at restoring any of these male-typical behaviors. However, the combined MPO/VTA implants were the most effective in restoring male-typical behaviors. In fact, a synergism between concurrent hormone action in the MPO and VTA was seen for mounting and urine preference. We interpret these data to indicate that androgen may act simultaneously in the MPO and VTA for more complete expression of some male-typical reproductive behaviors.

Animals↗
PubMed1995

Sleep-waking changes after c-fos antisense injections in the medial preoptic area.

The preoptic hypothalamus has been consistently implicated in the homeostatic regulation of sleep and waking. Recently, it was shown that periods of either spontaneous or forced wakefulness result in the induction in this region of the immediate-early gene c-fos. In this study, antisense oligonucleotides complementary to c-fos mRNA were employed to interfere with the expression of Fos protein. Injections in the rat medial preoptic area of c-fos antisense, but not of sense, oligonucleotides blocked the expression of Fos protein detected immunocytochemically. Rats receiving bilateral antisense injections showed a higher percentage of wakefulness the day after the injection than controls receiving sense or sham injections or antisense injections outside the preoptic area. These results suggest that blocking the expression of Fos protein in the preoptic hypothalamus may interfere with the homeostatic regulation of sleep and wakefulness.

Animals↗
PubMed1997

Estrogen regulation of GABA transmission in rat preoptic area.

The medial preoptic area represents a brain region where gonadal steroids act upon classical nuclear receptors to alter brain function. Of all the neuronal phenotypes shown to express estrogen receptors in the preoptic area, GABA neurones are the most abundant and known to be located in several nuclei of the medial preoptic area. Investigators utilising techniques capable of assessing endogenous GABA levels have shown that estrogen increases both basal and stimulated extracellular GABA concentrations within the preoptic area. Experiments have also shown that estrogen is able to modulate the actions of noradrenaline upon preoptic GABA neurones. The precise nature of estrogen's stimulatory influence on preoptic GABA concentrations is not understood fully but appears to involve changes in both the release and reuptake of GABA. As estrogen does not influence glutamic acid decarboxylase activity or gene expression in the preoptic area, the subcellular mechanism(s) through which estrogen enhances GABA release remain unknown. Recent investigations indicate that estrogen upregulates transcription of the GAT-1 GABA transporter gene in the preoptic area, and that this may contribute the stimulatory effect of estrogen on extracellular GABA concentrations. Further studies have identified effects of estrogen on GABA(A) receptor expression and ligand binding and, together with the above observations, demonstrate a coordinated and multifaceted upregulation of the preoptic GABA network by estrogen. It is suggested that estrogen acts directly upon GABA neurones expressing estrogen receptors to alter the dynamics of inhibitory transmission within specific neuronal networks of the preoptic area. This is likely to be of functional significance to the "feedback" influence of estrogen on the neural regulation of reproduction.

Animals↗
PubMed2003

Evidence for vesicular glutamate transporter synapses onto gonadotropin-releasing hormone and other neurons in the rat medial preoptic area.

The medial preoptic area is a key structure in the control of reproduction. Several data suggest that excitatory amino acids are involved in the regulation of this function and the major site of this action is the medial preoptic region. Data concerning the neuromorphology of the glutamatergic innervation of the medial preoptic area are fragmentary. The present investigations were focused on: (i) the morphology of the vesicular glutamate transporter 1 (VGluT1)- and vesicular glutamate transporter 2 (VGluT2)-immunoreactive nerve terminals, which are considered to be specific to presumed glutamatergic neuronal elements, in the medial preoptic area of rat; and (ii) the relationship between these glutamate transporter-positive endings and the gonadotropin-releasing hormone (GnRH) neurons in the region. Single- and double-label immunocytochemistry was used at the light and electron microscopic level. There was a weak to moderate density of VGluT1- and a moderate to intense density of VGluT2-immunoreactive elements in the medial preoptic area. Electron microscopy revealed that both VGluT1- and VGluT2-immunoreactive boutons made asymmetric type synaptic contacts with unlabelled neurons. VGluT2-labelled, but not VGluT1-labelled, axon terminals established asymmetric synaptic contacts on GnRH-immunostained neurons, mainly on their dendrites. The present findings are the first electron microscopic examinations on the glutamatergic innervation of the rat medial preoptic area. They provide direct neuromorphological evidence for the existence of direct glutamatergic innervation of GnRH and other neurons in the rat medial preoptic area.

Animals↗
PubMed1989

Branching projections from subcoeruleus area neurons to medial preoptic area and cervical spinal cord revealed by double retrograde neuronal labeling.

In this study we utilized a double retrograde axonal tracing technique to investigate the possible existence of collateralized axonal projections of subcoeruleus area neurons to both 'medial preoptic area (MPA) and cervical (C1-C3) spinal cord'. Following microinjections of fluorescent tracers (Fast blue (FB) and Diamidino yellow (DY) within MPA and C1-C3, substantial numbers of FB and DY single-labeled neurons as well as FB-DY double-labeled branched neurons have been found within subcoeruleus area.

Amidines↗
PubMed1980

Some characteristics of the darkly stained area of the medial preoptic area of rats.

Male rats have larger darkly stained area (DSA) within the medial preoptic area (MPOA) than female rats and this sex difference appears at the age of day 5 and continues to persist up to senescence. This sex dimorphism seems to be independent of gonadal hormones in the adult. In male rats the DSA has higher neuron density and larger neurons than the surrounding non-DSA. The total neuron number in MPOA is not different between young male rats and young female rats. In old age, neuron number of MPOA decreased in female rats but not in male rats.

Aging↗
PubMed1980

The preoptic area of the domestic fowl. II. Ultrastructure of the medial preoptic area.

Numerous secretory parvocellular perikarya were found in the preoptic region of the domestic fowl (Gallus gallus). The dense-core secretory vesicles belong to two categories: vesicles with a diameter of (i)80-90 nm and (ii) 110-140 nm. Scattered magnocellular elements display larger dense-core granules. The parvocellular neurons form unit-like clusters, showing also zones of direct apposition of neuronal membranes. The surrounding neuropil is rich in synaptic structures, formed by at least three types of axon terminals, distinguishable on the basis of vesicular morphology. These observations confirm the findings in other avian species. The hypothetical function of this system of peptidergic neurons in the rostral hypothalamus of birds is discussed.

Animals↗
PubMed1983

Effects of discrete lesions of the sexually dimorphic nucleus of the preoptic area or other medial preoptic regions on the sexual behavior of male rats.

The sexually dimorphic nucleus of the rat medial preoptic area (SDN-POA) has a volume five times larger in the adult male compared with that of the adult female. In the present study, the effects of discrete electrolytic destruction of the SDN-POA or other specific medial preoptic (MPOA) regions on masculine sexual behavior were determined in adult, sexually experienced male rats. Small lesions encompassing the SDN-POA had no effect on the maintenance of copulatory behavior. Lesions of similar size placed within the ventral or anterio-dorsal MPOA also did not consistently affect the display of masculine sexual behavior. However, animals that received small lesions within their dorsal MPOA showed a substantial, long-term decrease in number of mounts, intromissions, and ejaculations compared to these parameters in sham-lesioned control rats, thus indicating a lesion-induced disruption of those neural mechanisms mediating these behaviors. Collectively these data suggest that the SDN-POA is not critical for a full expression of male sexual behavior and that the dorsal MPOA may be more important than other MPOA regions for copulatory behavior.

Animals↗
PubMed1989

[Ultrastructural organization of the hypothalamic medial preoptic area and its changes under the effect of pyrogens].

In order to study structural bases of central mechanisms of thermoregulation, a comparative electron microscopic analysis of various cellular groups in one of thermosensitive zones of the cat hypothalamic area--the medial preoptic area--have been carried out under conditions of experimental fever. The latter is produced by injection of pyrogen of bacterial origin--pyrogenal--to the animals. Pyrogenal, increasing the body temperature, produces a stimulatory effect on various cellular elements, first of all on leucocytes, monocytes and macrophages in the medial preoptic area, as well as on endotheliocytes of the terminal vessels. Under pyrogenal effect activation of microglial cells and pericytes also takes place, and as a result of the rearrangements, occurring in the structure, they change into macrophages. This is an evidence of their active participation in the immune protection of the brain. According to the data from other investigations, all these activated cells produce peptide interleukin-1, one of the mediators of fever and stimulator of the immune system. Pyrogenal is stated to produce a stimulating effect on the astroglia and on some neurons of the medial preoptic area, that respond with cytoplasm increase and accumulation of numerous organelles. The reactive changes at fever in some neurons of the medial preoptic area can demonstrate that they belong to the thermosensitive pool. A conclusion is made, concerning a complex effect of pyrogenal, that results in a cooperative response of a number of cellular systems of the organism.

Animals↗
PubMed2002

Fos expression induced by warming the preoptic area in rats.

The preoptic area (POA) occupies a crucial position among the structures participating in thermoregulation, but we know little about its efferent projections for controlling various effector responses. In this study, we used an immunohistochemical analysis of Fos expression during local warming of the preoptic area. To avoid the effects of anesthesia or stress, which are known to elicit Fos induction in various brain regions, we used a novel thermode specifically designed for chronic warming of discrete brain structures in freely moving rats. At an ambient temperature of 22 degrees C, local POA warming increased Fos immunoreactivity in the supraoptic nucleus (SON) and the periaqueductal gray matter (PAG). Exposure of animals to an ambient temperature of 5 degrees C induced Fos immunoreactivity in the magnocellular paraventricular nucleus (mPVN) and the dorsomedial region of the hypothalamus (DMH). Concurrent warming of the POA suppressed Fos expression in these areas. These findings suggest that thermal information from the preoptic area sends excitatory signals to the SON and the PAG, and inhibitory signals to the mPVN and the DMH.

Animals↗
PubMed2001

GABA exerts opposite influence on warm and cold sensitive neurons in medial preoptic area in rats.

The preoptic area regulates body temperature. GABA-ergic terminals and receptors are present in this area. Local microinjection studies have shown that GABA, its agonist, and its antagonist in this area may modulate body temperature. However, there are warm and cold sensitive neurons, and they are known to be affected by local and peripheral temperatures. In order to understand the mechanism of action of GABA in temperature regulation at the cellular level it was necessary to study the effect of GABA on individual thermosensitive neurons in in vivo preparations. Hence, in this study the responses of preoptic area thermosensitive and insensitive neurons to microiontophoretic application of picrotoxin, a GABA-A antagonist, were studied in anaesthetized rats. It was observed that a majority of both the thermosensitive and insensitive neurons were affected by microiontophoretic application of picrotoxin. Although almost an equal number of cold and warm sensitive neurons were affected, a majority of the cold sensitive neurons were excited, while a majority of the warm sensitive neurons were inhibited by picrotoxin. The results suggested that in normal conditions GABA acts through GABA-A receptor in modulating the spontaneous activity of thermosensitive neurons in the preoptic area. Furthermore, the results of the present study taken together with other reports suggest that normally GABA exerts a direct inhibitory action on the cold sensitive neurons, while it acts on presynaptic heteroreceptors, possibly on norepinephrinergic afferent input terminals on the warm sensitive neurons, for mediating its action.

Animals↗
PubMed1992

Identification of a sexually dimorphic neural population immunoreactive for calcitonin gene-related peptide (CGRP) in the rat medial preoptic area.

The medial preoptic area (MPOA) of the rat exhibits morphological sex differences and is implicated in sex-specific functioning and behaviour. Using immunocytochemistry, the distribution and numbers of cells containing calcitonin gene-related peptide (CGRP) were examined in the MPOA of adult male and female rats. In the intact female rat, CGRP-immunoreactive (-IR) cells were found in a continuum within the MPOA extending from the caudal aspects of the organum vasculosum of the lamina terminalis through the anteroventral periventricular nucleus (AVPv) to the region of the medial preoptic nucleus (MPN). An additional small group of CGRP-IR cells was noted at the level of the caudal MPNin the ventrolateral (VL) region. Compared with males, the AVPv and MPN regions of the female contained over 25-fold more CGRP-IR cells (P < 0.01). The VL region contained similar numbers of CGRP-IR cells in both sexes. Ovariectomy 1 month earlier, with or without subsequent 17-beta estradiol treatment, had no effect on the numbers or distribution of CGRP-IR cells in the MPOA. Gonadectomy of male rats resulted in a significant increase (P < 0.01) in the numbers of CGRP-IR cells in the AVPv and MPN regions. Subsequent administration of testosterone propionate for 1 week reduced (P < 0.05) numbers of CGRP-IR cells to levels observed in the intact male. Neurones containing CGRP in the VL group were not altered by gonadal steroid manipulation. This study shows that CGRP neurones in the AVPv/MPN region are sexually dimorphic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Estrogen receptor beta modulates estradiol induction of progestin receptor immunoreactivity in male, but not in female, mouse medial preoptic area.

The medial preoptic area (mPOA) of the hypothalamus contains many neurons that express estrogen receptor alpha (ER) and/or ERbeta. We examined the distribution of these receptors and assessed responses to estradiol (E2) in the adult mouse mPOA. Gonadectomized adult male and female mice were killed, and brains were processed for immunocytochemistry for ERalpha and ERbeta. More ERalpha immunoreactive (-ir) than ERbeta-ir neurons were present in the mouse mPOA. Numbers of ERalpha-ir cells were equivalent between males and females, but males had significantly more ERbeta-ir neurons than females. Using breeders that were heterozygous for disrupted ERalpha and ERbeta genes, we produced offspring with varying numbers (0, 1, or 2) of functional and disrupted ERalpha and ERbeta genes. After gonadectomy, half the mice received E2 for 5 d before they were killed. Estradiol treatment, sex, and genotype each had independent effects on numbers of PR-ir neurons in the mPOA. In all cases, brains that lacked at least one functional copy of ERalpha had reduced PR-ir cell numbers. In gonadectomized, untreated mice, one functional copy of the ERbeta gene was correlated with the largest amount of PR-ir. After E2 treatment, both sexes had greatly enhanced numbers of PR-ir containing neurons. In females, maximal PR induction required the presence of at least one functional copy of ERalpha, whereas in males, at least a single copy of both functional ERbeta and ERalpha genes was needed for maximal PR-ir induction. We hypothesize that the two ERs have dependent and independent roles in sexual differentiation of neuroendocrine function.

Animals↗
PubMedDate not supplied

Gating of the dorsal penile nerve inputs by norepinephrine at the medial preoptic area in rats.

The medial preoptic area neurons related to male sexual behaviour in rats were identified by their responses to dorsal penile nerve stimulation. These neurons were further tested with norepinephrine applied iontophoretically. From the 21 medial preoptic area neurons recorded in urethane anaesthetized rats, 17 neurons responded to dorsal penile nerve stimulation. Excitatory and inhibitory responses were found in almost equal number of neurons. 14 neurons responded to norepinephrine application, out of which six neurons were excited and eight were inhibited. The direction of changes produced by dorsal penile nerve stimulation and norepinephrine application were similar in 10 neurons. The results suggest that the sensory inputs from the genitalia are possibly gated by norepinephrine at the level of the medial preoptic area. Afferent information from the genitalia carried by dorsal penile nerve and the availability of norepinephrine at the level of the medial preoptic area probably help in maintaining adequate level of sexual arousal.

Action Potentials↗
PubMed2005

Effects on sleep of microdialysis of adenosine A1 and A2a receptor analogs into the lateral preoptic area of rats.

Evidence suggests that adenosine (AD) is an endogenous sleep factor. The hypnogenic action of AD is mediated through its inhibitory A1 and excitatory A2A receptors. Although AD is thought to be predominantly active in the wake-active region of the basal forebrain (BF), a hypnogenic action of AD has been demonstrated in several other brain areas, including the preoptic area. We hypothesized that in lateral preoptic area (LPOA), a region with an abundance of sleep-active neurons, AD acting via A1 receptors would induce waking by inhibition of sleep-active neurons and that AD acting via A2A receptors would promote sleep by stimulating the sleep-active neurons. To this end, we studied the effects on sleep of an AD transport inhibitor, nitrobenzyl-thio-inosine (NBTI) and A1 and A2A receptor agonists/antagonists by microdialyzing them into the LPOA. The results showed that, in the sleep-promoting area of LPOA: 1) A1 receptor stimulation or inhibition of AD transport by NBTI induced waking and 2) A2A receptor stimulation induced sleep. We also confirmed that NBTI administration in the wake promoting area of the BF increased sleep. The effects of AD could be mediated either directly or indirectly via interaction with other neurotransmitter systems. These observations support a hypothesis that AD mediated effects on sleep-wake cycles are site and receptor dependent.

Adenosine↗