Dimorphic Nucleus Of Preoptic Area Research Articles

A Potential Role for the Existence of Pericytes in the Neurovascular Unit of the Sexually Dimorphic Nucleus of the Rat Preoptic Area to Control Blood-Brain Barrier Function.

The present study aimed at determining pericytes, a missing component in the previously proposed living neurovascular unit (NVU) of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in rats. Calbindin D28K-immunoreactivities (CB28-irs) were used to delineate the SDN-POA in which CD13-immunoreactivities (CD13-irs) or alpha-smooth muscle actinimmunoreactivities (αSMA-irs), two pericyte biomarkers serving the indexes of pericytes, were tagged using two adjacent brain sections (90-micron intervals). In addition, the nestinimmunoreactive (nestin-ir) cells in the SDN-POA were counted as pericytes referring to additional standards: location and nucleic and cellular morphology. Male SDN-POA volume (5.0±0.3x10-3 mm3) was significantly larger than the female (1.7±0.3x10-3 mm3). Within the SDN-POA, the CD13-irs were characterized as dots, densely packed and net-like in distribution, while the αSMAirs, excluding pipe-like or circular structures, appeared as short rod-like structures that were sparsely distributed. The immunoreactive counts of alpha-smooth muscle actin were 353±57/mm2 in males and 124±46/mm2 in females (p<0.05). On the other hand, densities of the dot-like CD13-irs were similar between males (4009±301/mm2) and females (4018±414/ mm2). There was no difference between the male and the female in the nestin-ir pericyte count in the SDN-POA. In conclusion, the present study adds new information concerning pericytes to the living NVU of the SDN-POA. There is a difference of sex in the count of the αSMA-irs in the living NVU of the SDN-POA. However, why such a difference exists warrants further investigations.

Anti-Müllerian hormone may regulate the number of calbindin-positive neurons in the sexually dimorphic nucleus of the preoptic area of male mice

BackgroundThe male brain is putatively organised early in development by testosterone, with the sexually dimorphic nucleus of the medial preoptic area (SDN) a main exemplifier of this. However, pubescent neurogenesis occurs in the rat SDN, and the immature testes secrete anti-Müllerian hormone (AMH) as well as testosterone. We have therefore re-examined the development of the murine SDN to determine whether it is influenced by AMH and/or whether the number of calbindin-positive (calbindin+ve) neurons in it changes after pre-pubescent development.MethodsIn mice, the SDN nucleus is defined by calbindin+ve neurons (CALB-SDN). The number and size of the neurons in the CALB-SDN of male and female AMH null mutant (Amh-/-) mice and their wild-type littermates (Amh+/+) were studied using stereological techniques. Groups of mice were examined immediately before the onset of puberty (20 days postnatal) and at adulthood (129–147 days old).ResultsThe wild-type pre-pubertal male mice had 47% more calbindin+ve neurons in the CALB-SDN than their female wild-type littermates. This sex difference was entirely absent in Amh-/- mice. In adults, the extent of sexual dimorphism almost doubled due to a net reduction in the number and size of calbindin+ve neurons in females and a net increase in neuron number in males. These changes occurred to a similar extent in the Amh-/- and Amh+/+ mice. Consequently, the number of calbindin+ve neurons in Amh-/- adult male mice was intermediate between Amh+/+ males and Amh+/+ females. The sex difference in the size of the neurons was predominantly generated by a female-specific atrophy after 20 days, independent of AMH.ConclusionsThe establishment of dimorphic cell number in the CALB-SDN of mice is biphasic, with each phase being subject to different regulation. The second phase of dimorphism is not dependent on the first phase having occurred as it was present in the Amh-/- male mice that have female-like numbers of calbindin+ve neurons at 20 days. These observations extend emerging evidence that the organisation of highly dimorphic neuronal networks changes during puberty or afterwards. They also raise the possibility that cellular events attributed to the imprinting effects of testosterone are mediated by AMH.

Distribution of retinoic acid receptor-α immunoreactivity in the human hypothalamus

Retinoids, a family of molecules that is derived from vitamin A, are involved in a complex signaling pathway that regulates gene expression and controls neuronal differentiation in the central nervous system. The physiological actions of retinoids are mainly mediated by retinoic acid receptors. Here we describe the distribution of retinoic acid receptor α (RARα) in the human hypothalamus by immunohistochemistry. RARα immunoreactivity showed a widespread pattern throughout the hypothalamus, with high density in the suprachiasmatic nucleus (SCN), paraventricular nucleus (PVN), supraoptic nucleus (SON), infundibular nucleus and medial mamillary nucleus. No staining was observed in the sexually dimorphic nucleus of preoptic area, tuberomamillary nucleus and lateral hypothalamic area. RARα was co-localized with vasopressin (AVP) neurons in the SCN, PVN and SON, and co-localized with corticotropin releasing hormone (CRH) neurons in the PVN. These findings provide a neurobiological basis for the participation of retinoids in the regulation of various hypothalamic functions. As shown earlier, the co-localization of RARα in CRH neurons suggests that retinoids might directly modulate the hypothalamus-pituitary-adrenal axis in the PVN, which may have implications for the stress response and its involvement in mood disorders. Functional studies in the other sites of RARα localization have to follow in the future.

Transient Transcription of the Somatostatin Gene at the Time of Estrogen-Dependent Organization of the Sexually Dimorphic Nucleus of the Rat Preoptic Area

In situ hybridization detected a transient, sex-specific transcription of somatostatin gene in the central part of the rat medial preoptic nucleus, which coincides with the sexually dimorphic nucleus of the preoptic area (SDN-POA), during, but not after, the establishment of sex difference. On postnatal d 1 (day of birth), somatostatin mRNA was detected in the SDN-POA of both sexes. On d 8 through 35, the area of somatostatin mRNA-positive cells was significantly larger in males than in females. In males the area attained its maximum size on d 15 and diminished gradually thereafter. In females the area did not change in size during this period. On d 60 expression of somatostatin mRNA was low and not different between sexes. Throughout the observed period, Nissl staining and calbindin immunohistochemistry enabled visualization of the typical SDN-POA in the same region. As with Nissl staining and calbindin immunohistochemistry, somatostatin mRNA hybridization on d 15 revealed a reversal of the sexual dimorphism in the size of the SDN-POA in males that had been neonatally orchidectomized or females given estrogen as pups, showing that sex steroid milieu during the organizational period determines the area occupied by somatostatin mRNA-positive cells. Sex-specific, transient transcription of the somatostatin gene may causally relate to the estrogen-dependent organization of the SDN-POA.

Lack of maternal dietary exposure effects of bisphenol A and nonylphenol during the critical period for brain sexual differentiation on the reproductive/endocrine systems in later life.

Two potential endocrine-disrupting chemicals, bisphenol A (BPA) and nonylphenol (NP), were assessed for their long-lasting effects on endocrine/reproductive systems following transplacental and lactational exposure to rat offspring during a time-window that included the critical period for brain sexual differentiation. Each chemical was mixed with diet at concentrations of 60, 600 and 3000 ppm and was provided to maternal Sprague-Dawley rats from gestational day (GD) 15 to postnatal day (PND) 10. Ethinylestradiol (EE) at 0.5 ppm was used as an estrogenic reference drug. During pregnancy and lactation, including the exposure period, a soy-free rodent diet was provided to eliminate possible modification of the study results by plant-derived phytoestrogens. Effects on endocrine/reproductive systems were evaluated by examining the anogenital distance, organ weights before puberty, onset of puberty, estrous cyclicity, and organ weights and histopathology of adult endocrine organs (at 11 weeks of age), as well as the volume of the sexually dimorphic nucleus of preoptic area. Both NP and BPA, at high doses, caused decreases in maternal body weights and retardation of offspring growth, but neither affected any of the endocrine/reproductive endpoints of offspring, whereas EE induced irreversible changes in estrous cyclicity and histopathology of ovaries and uterus of adult females. The results indicated that maternal dietary exposure to NP or BPA at concentrations up to 3000 ppm from GD 15 through PND 10 do not exert any apparent adverse effects on the endocrine/reproductive systems of offspring.

Impact of dietary exposure to methoxychlor, genistein, or diisononyl phthalate during the perinatal period on the development of the rat endocrine/reproductive systems in later life.

To evaluate the impact of dietary exposure to endocrine disrupting chemicals (EDCs) during the sensitive period of brain sexual differentiation, maternal Sprague-Dawley rats were fed three representative chemicals, methoxychlor (MXC; 24, 240, and 1200 ppm), genistein (GEN; 20, 200, and 1000 ppm), or diisononyl phthalate (DINP; 400, 4000, and 20,000 ppm), from gestational day 15 to postnatal day 10. Soy-free diet was used as a basal diet to eliminate possible estrogenic effects from the standard diet. Offspring were examined in terms of anogenital distances, prepubertal organ weights, onset of puberty, estrous cyclicity, and organ weights and histopathology of endocrine organs at adult stage (week 11) as well as the volumes of sexually dimorphic nucleus of preoptic area (SDN-POA). All chemicals caused signs of maternal toxicity at high doses. MXC, at 1200 ppm, facilitated and delayed the onset of puberty in females and males, respectively, females also showing endocrine disrupting effects thereafter, such as irregular estrous cyclicity and histopathological alterations in the reproductive tract and anterior pituitary. GEN, at all doses, reduced body weight (BW) at week 11, but did not affect endocrine parameters. Treatment with DINP at 20,000 ppm resulted in degeneration of meiotic spermatocytes and Sertoli cells in the testis and decrease of corpora lutea in the ovary at week 11, although changes remained minimal or slight. The SDN-POA volume remained unchanged with all three chemicals. The results demonstrated that perinatal dietary exposure to EDCs for a limited period causes endocrine disruption in offspring only at high doses.

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.