The increase in the number of amylin neurons in the medial preoptic area throughout the lactational period and its relationship with melanin-concentrating hormone.

The amylin and the melanin-concentrating hormone [MCH] are two peptides related to energetic homeostasis. During lactation, it is possible to locate neurons expressing these peptides in the preoptic area of rat dams. In addition, it was demonstrated that the number of MCH neurons in this region is modulated by litter size. Taken together, the aims of this work were (1) to verify the time course of amylin immunoreactivity during lactation; (2) to verify whether litter size modulates the number of amylin-ir neurons (3) to verify whether there is colocalization between the amylin-ir and MCH-ir neurons. Our results show that (1) there is an increase in the number of amylin-ir neurons during lactation, which reaches a peak at postpartum day 19 and drastically reduces after weaning; (2) there is no correlation between litter size and the number of amylin-ir neurons; and (3) there is minimal overlap between amylin-ir and MCH-ir neurons.

Melanin-concentrating hormone regulation by estradiol and progesterone in the incerto-hypothalamic area.

Melanin-concentrating hormone (MCH) is a peptide related to the reproductive function by interacting with the hypothalamus-pituitary-gonadal axis. In addition to the MCH central production, it is also found in the blood with a putative role as a neurohormone. Thereby, our focus is on steroid hormones' role in regulating centrally produced MCH in the incerto-hypothalamic area (IHy) and the peripheral MCH in the serum. For this, we investigated the effect of estradiol and/or progesterone injection on the number of MCH immunoreactive (MCH-ir) neurons at the IHy and serum levels. For further study of the role of progesterone, we analyzed the effect of blockade of progesterone receptors by its antagonist on MCH-ir neurons at the IHy and serum. To identify whether such regulation over MCH is established before sexual maturation, we assessed the effect of peripubertal removal of steroid hormones on MCH-ir neurons at the IHy and serum levels at adult age. Our results show that injecting estradiol in ovariectomized female rats reduces the number of MCH-ir neurons in the IHy, in addition to its serum levels. Blockade of progesterone receptors in intact females increases the number of MCH-ir neurons in the IHy and its serum concentration. The regulation of these hormones over the MCH peptidergic system is established before sexual maturation, once the peripubertal removal of the ovaries changes the serum levels of MCH and the number of MCH-ir neurons in the IHy of adult females. Such results support the inhibitory role of steroid hormones over the MCH system.

The effect of estrogen and progesterone on melanin-concentrating hormone producing-neurons in brain areas related to reproductive behavior in lactating dams.

The hypothalamus plays a role in reproductive cycle control, and it is a site of action of steroid hormones. Throughout the production of melanin-concentrating hormone (MCH), the hypothalamus shows adaptive changes during lactation. Therefore, in this work, we aimed to test the effects of estrogen and progesterone manipulation on MCH-immunoreactive (ir) neurons in hypothalamic brain areas related to reproductive behavior and on the MCH serum concentration. Our results show that the removal of steroid hormones by ovariectomy increases the number of MCH-ir neurons in the medial preoptic area (MPOA) and incerto-hypothalamic area (IHy) but not in the anterior part of the paraventricular nucleus of the hypothalamus (PVHa). The MCH in the serum levels also increases. In accordance, the injection of estradiol alone or estradiol and progesterone decreased the number of MCH-ir neurons in the MPOA and IHy, as well as its serum levels. The MPOA and IHy are the brain areas targeted by the steroid hormone inhibitory effect of the MCH system during lactation. This effect is also reflected in the MCH serum levels.

Effects of ovariectomy on the inputs from the medial nucleus of the amygdala to the ventromedial nucleus of the hypothalamus in young adult rats.

During puberty, sexual hormones induce crucial changes in neural circuit organization, leading to significant sexual dimorphism in adult behaviours. The ventrolateral division of the ventromedial nucleus of the hypothalamus (VMHvl) is the major neural site controlling the receptive component of female sexual behaviour, which is dependent on ovarian hormones. The inputs to the VMHvl, originating from the medial nucleus of the amygdala (MeA), transmit essential information to trigger such behaviour. In this study, we investigated the projection pattern of the MeA to the VMHvl in ovariectomized rats at early puberty. Six-week-old Sprague-Dawley rats were ovariectomized (OVX) and, upon reaching 90 days of age, were subjected to iontophoretic injections of the neuronal anterograde tracer Phaseolus vulgaris leucoagglutinin into the MeA. Projections from the MeA to the VMHvl and to other structures included in the neural circuit responsible for female sexual behaviour were analysed in the Control and OVX groups. The results of the semi-quantitative analysis showed that peripubertal ovariectomy reduced the density of intra-amygdalar fibres. The stereological estimates, however, failed to find changes in the organization of the terminal fields of nerve fibres from the MeA to the VMHvl in the adult. The present data show that ovariectomized rats during the peripubertal phase did not undergo significant changes in MeA fibres reaching the VMHvl; however, they suggest a possible effect of ovariectomy on MeA connectivity under amygdalar subnuclei.

Effects of ovariectomy on inputs from the medial preoptic area to the ventromedial nucleus of the hypothalamus of young adult rats.

Puberty is an important phase of development when the neural circuit organization is transformed by sexual hormones, inducing sexual dimorphism in adult behavioural responses. The principal brain area responsible for the control of the receptive component of female sexual behaviour is the ventrolateral division of the ventromedial nucleus of the hypothalamus (VMHvl), which is known for its dependency on ovarian hormones. Inputs to the VMHvl originating from the medial preoptic nucleus (MPN) are responsible for conveying essential information that will trigger such behaviour. Here, we investigated the pattern of the projection of the MPN to the VMHvl in rats ovariectomized at the onset of puberty. Sprague Dawley rats were ovariectomized (OVX) at puberty and then subjected to iontophoretic injections of the neuronal anterograde tracer Phaseolus vulgaris leucoagglutinin into the MPN once they reached 90 days of age. This study analysed the connectivity pattern established between the MPN and the VMH that is involved in the neuronal circuit responsible for female sexual behaviour in control and OVX rats. The data show the changes in the organization of the connections observed in the OVX adult rats that displayed a reduced axonal length for the MPN fibres reaching the VMHvl, suggesting that peripubertal ovarian hormones are relevant to the organization of MPN connections with structures involved in the promotion of female sexual behaviour.

Litter size determines the number of melanin-concentrating hormone neurons in the medial preoptic area of Sprague Dawley lactating dams.

Melanin-concentrating hormone [MCH] is an important neuromodulator related to motivated behaviors. The MCH-containing neurons are mainly located in the lateral hypothalamic area, zona incerta, and incerto-hypothalamic area. In the medial preoptic area [MPOA], a key region for the regulation of maternal behavior, Pmch mRNA expression and MCH synthesis can be detected exclusively during the lactation period. As litter size affects different parameters of maternal physiology, the aim of this study was to verify whether litter size can modulate the number of MCH-containing neurons in the MPOA of lactating rats. The dams were divided into the following groups: postpartum day 12, 15, or 19, with a large, small or reduced litter. Our results show that the number of MCH-immunoreactive neurons in the MPOA is positively correlated with the number of pups in the litter and that artificially reducing the number of pups can also decrease the number of MCH-immunoreactive neurons in the MPOA.

Melanin-concentrating hormone and sleep.

The melanin-concentrating hormone (MCH) is an essential neuromodulator involved with homeostatic regulation and motivated behaviors. The majority of MCH neurons are localized within the zona incerta, lateral hypothalamic and incerto-hypothalamic areas but others regions, as the olfactory turbecle, the laterodorsal tegmental nucleus, the paramediam pontine reticular formation and the medial preoptic area, can also express the peptide depending on the gender and metabolic state of the animal. If the MCH on these novel sites of expression are also related with the control of wake-sleep cycle will be discuss in this review.