"HLA-C: evolution, epigenetics, and pathological implications in the major histocompatibility complex".

HLA-C, a gene located within the major histocompatibility complex, has emerged as a prominent target in biomedical research due to its involvement in various diseases, including cancer and autoimmune disorders; even though its recent addition to the MHC, the interaction between HLA-C and KIR is crucial for immune responses, particularly in viral infections. This review provides an overview of the structure, origin, function, and pathological implications of HLA-C in the major histocompatibility complex. In the last decade, we systematically reviewed original publications from Pubmed, ScienceDirect, Scopus, and Google Scholar. Our findings reveal that genetic variations in HLA-C can determine susceptibility or resistance to certain diseases. However, the first four exons of HLA-C are particularly susceptible to epigenetic modifications, which can lead to gene silencing and alterations in immune function. These alterations can manifest in diseases such as alopecia areata and psoriasis and can also impact susceptibility to cancer and the effectiveness of cancer treatments. By comprehending the intricate interplay between genetic and epigenetic factors that regulate HLA-C expression, researchers may develop novel strategies for preventing and treating diseases associated with HLA-C dysregulation.

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.

Acute intrahippocampal administration of melanin-concentrating hormone impairs memory consolidation and decreases the expression of MCHR-1 and TrkB receptors.

Interest in the role of melanin-concentrating hormone (MCH) in memory processes has increased in recent years, with some studies reporting memory-enhancing effects, while others report deleterious effects. Due to these discrepancies, this study seeks to provide new evidence about the role of MCH in memory consolidation and its relation with BDNF/TrkB system. To this end, in the first experiment, increased doses of MCH were acutely administered in both hippocampi to groups of male rats (25, 50, 200, and 500 ng). Microinjections were carried out immediately after finishing the sample trial of two hippocampal-dependent behavioral tasks: the Novel Object Recognition Test (NORT) and the modified Elevated Plus Maze (mEPM) test. Results indicated that a dose of 200 ng of MCH or higher impaired memory consolidation in both tasks. A second experiment was performed in which a dose of 200 ng of MCH was administered alone or co-administered with the MCHR-1 antagonist ATC-0175 at the end of the sample trial in the NORT. Results showed that MCH impaired memory consolidation, while the co-administration with ATC-0175 reverted this detrimental effect. Moreover, MCH induced a significant decrease in hippocampal MCHR-1 and TrkB expression with no modification in the expression of BDNF and NMDA receptor subunits NR1, NR2A, and NR2B. These results suggest that MCH in vivo elicits pro-amnesic effects in the rat hippocampus by decreasing the availability of its receptor and TrkB receptors, thus linking both endogenous systems to memory processes.

MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil.

Background: Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome. Methods: SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started. Results: We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24). Conclusion: Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.

Melanin-concentrating hormone regulates the hypercapnic chemoreflex by acting in the lateral hypothalamic area.

NEW FINDINGS: What is the central question of this study? Melanin-concentrating hormone (MCH) suppresses the hypercapnic chemoreflex: what is the mechanism by which this effect is produced? What is the main finding and its importance? MCH acting in the lateral hypothalamic area but not in the locus coeruleus in rats, in the light period, attenuates the hypercapnic chemoreflex. The data provide new insight into the role of MCH in the modulation of the hypercapnic ventilatory response. ABSTRACT: Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide involved in a broad range of homeostatic functions including regulation of the hypercapnic chemoreflex. We evaluated whether MCH modulates the hypercapnic ventilatory response by acting in the lateral hypothalamic area (LHA) and/or in the locus coeruleus (LC). Here, we measured pulmonary ventilation ( V ̇ E ${\dot V_{\rm{E}}}$ ), body temperature, electroencephalogram (EEG) and electromyogram (EMG) of unanaesthetized adult male Wistar rats before and after microinjection of MCH (0.4 mM) or MCH receptor 1 (MCH1-R) antagonist (SNAP-94847; 63 mM) into the LHA and LC, in room air and 7% CO2 conditions during wakefulness and sleep in the dark and light periods. MCH intra-LHA caused a decreased CO2 ventilatory response during wakefulness and sleep in the light period, while SNAP-94847 intra-LHA increased this response, during wakefulness in the light period. In the LC, MCH or the MCH1-R antagonist caused no change in the hypercapnic ventilatory response. Our results suggest that MCH, in the LHA, exerts an inhibitory modulation of the hypercapnic ventilatory response during the light-inactive period in rats.

Convergent Epigenetic Mechanisms Avoid Constitutive Expression of Immune Receptor Gene Subsets.

The gene pool encoding PRR and NLR immune receptors determines the ability of a plant to resist microbial infections. Basal expression of these genes is prevented by diverse mechanisms since their hyperactivity can be harmful. To approach the study of epigenetic control of PRR/NLR genes we here analyzed their expression in mutants carrying abnormal repressive 5-methyl cytosine (5-mC) and histone 3 lysine 9 dimethylation (H3K9me2) marks, due to lack of MET1, CMT3, MOM1, SUVH4/5/6, or DDM1. At optimal growth conditions, none of the mutants showed basal expression of the defense gene marker PR1, but all of them had greater resistance to Pseudomonas syringae pv. tomato than wild type plants, suggesting they are primed to stimulate immune cascades. Consistently, analysis of available transcriptomes indicated that all mutants showed activation of particular PRR/NLR genes under some growth conditions. Under low defense activation, 37 PRR/NLR genes were expressed in these plants, but 29 of them were exclusively activated in specific mutants, indicating that MET1, CMT3, MOM1, SUVH4/5/6, and DDM1 mediate basal repression of different subsets of genes. Some epigenetic marks present at promoters, but not gene bodies, could explain the activation of these genes in the mutants. As expected, suvh4/5/6 and ddm1 activated genes carrying 5-mC and H3K9me2 marks in wild type plants. Surprisingly, all mutants expressed genes harboring promoter H2A.Z/H3K27me3 marks likely affected by the chromatin remodeler PIE1 and the histone demethylase REF6, respectively. Therefore, MET1, CMT3, MOM1, SUVH4/5/6, and DDM1, together with REF6, seemingly contribute to the establishment of chromatin states that prevent constitutive PRR/NLR gene activation, but facilitate their priming by modulating epigenetic marks at their promoters.

Neonatal Reference Intervals for the Complete Blood Count Parameters MicroR and HYPO-He: Sensitivity Beyond the Red Cell Indices for Identifying Microcytic and Hypochromic Disorders.

OBJECTIVE: To create neonatal reference intervals for the MicroR and HYPO-He complete blood count (CBC) parameters and to test whether these parameters are sensitive early markers of disease at early stages of microcytic/hypochromic disorders while the CBC indices are still normal. STUDY DESIGN: We retrospectively collected the CBC parameters MicroR and HYPO-He, along with the standard CBC parameters, from infants aged 0-90 days at Intermountain Healthcare hospitals using Sysmex hematology analyzers. We created reference intervals for these parameters by excluding values from neonates with proven microcytic disorders (ie, iron deficiency or alpha thalassemia) from the dataset. RESULT: From >11 000 CBCs analyzed, we created reference intervals for MicroR and HYPO-He in neonates aged 0-90 days. The upper intervals are considerably higher in neonates than in adults, validating increased anisocytosis and polychromasia among neonates. Overall, 52% of neonates with iron deficiency (defined by reticulocyte hemoglobin equivalent <25 pg) had a MicroR >90% upper interval (relative risk, 4.14; 95% CI, 3.80-4.53; P < .001), and 68% had an HYPO-He >90% upper interval (relative risk, 6.64; 95% CI, 6.03-7.32; P < .001). These 2 new parameters were more sensitive than the red blood cell (RBC) indices (P < .001) in identifying 24 neonates with iron deficiency at birth. CONCLUSIONS: We created neonatal reference intervals for MicroR and HYPO-He. Although Sysmex currently designates these as research use only in the US, they can be measured as part of a neonate's CBC with no additional phlebotomy volume or run time and can identify microcytic and hypochromic disorders even when the RBC indices are normal.

Ecotoxicity of pesticides and semiochemicals used for control and prevention of conifer bark beetle (Dendroctonus spp.) outbreaks.

Application of pyrethroid pesticides and semiochemicals are two treatments used worldwide to control conifer bark beetles (Dendroctonus spp.); their residues can reach water reservoirs and water currents through run off and affect non-target organisms such as freshwater invertebrates. Therefore, we assessed the 48-h lethal toxicity, chronic toxicity (reproduction inhibition), and bioaccumulation of three pyrethroid pesticides (bifenthrin, cypermethrin, and deltamethrin) and two semiochemicals (verbenone and 3-methyl-2-cyclohexen-1-one) in two freshwater invertebrates: the cladoceran Alona guttata and the rotifer Lecane papuana. Bifenthrin was the most toxic of the five chemical compounds tested followed by deltamethrin and then cypermethrin, which was the least toxic pyrethroid for both species. Semiochemicals were far less toxic than pyrethroids and verbenone was most toxic than 3-methyl-2-cyclohexen-1-one for both species. For the rotifer Lecane papuana, the pyrethroid with the highest Bioconcentration Factor was bifenthrin, and for the semiochemicals it was 3-methyl-2-cyclohexen-1-one. For the cladoceran Alona guttata, the pyrethroid with the highest bioconcentration factor was cypermethrin and for the semiochemicals it was verbenone. The pyrethroid with highest body burdens both lethal and chronic was cypermethrin. Semiochemicals showed lethal and chronic body burdens 12-fold higher than pyrethroids and were therefore less toxic than pyrethroids. These results showed that the semiochemicals verbenone and 3-methyl-2-cyclohexen-1-one are a safe tool for the freshwater invertebrates tested when compared with pyrethroid pesticides. Cypermethrin was the least toxic of the pyrethroids tested and therefore could be considered as a good candidate to control outbreaks of the conifer bark beetle.

Ciliary melanin-concentrating hormone receptor 1 (MCHR1) is widely distributed in the murine CNS in a sex-independent manner.

Melanin-concentrating hormone (MCH) is a ubiquitous vertebrate neuropeptide predominantly synthesized by neurons of the diencephalon that can act through two G protein-coupled receptors, called MCHR1 and MCHR2. The expression of Mchr1 has been investigated in both rats and mice, but its synthesis remains poorly described. After identifying an antibody that detects MCHR1 with high specificity, we employed immunohistochemistry to map the distribution of MCHR1 in the CNS of rats and mice. Multiple neurochemical markers were also employed to characterize some of the neuronal populations that synthesize MCHR1. Our results show that MCHR1 is abundantly found in a subcellular structure called the primary cilium, which has been associated, among other functions, with the detection of free neurochemical messengers present in the extracellular space. Ciliary MCHR1 was found in a wide range of areas, including the olfactory bulb, cortical mantle, striatum, hippocampal formation, amygdala, midline thalamic nuclei, periventricular hypothalamic nuclei, midbrain areas, and in the spinal cord. No differences were observed between male and female mice, and interspecies differences were found in the caudate-putamen nucleus and the subgranular zone. Ciliary MCHR1 was found in close association with several neurochemical markers, including tyrosine hydroxylase, calretinin, kisspeptin, estrogen receptor, oxytocin, vasopressin, and corticotropin-releasing factor. Given the role of neuronal primary cilia in sensing free neurochemical messengers in the extracellular fluid, the widespread distribution of ciliary MCHR1, and the diverse neurochemical populations who synthesize MCHR1, our data indicate that nonsynaptic communication plays a prominent role in the normal function of the MCH system.

Regulation and neurochemical identity of melanin-concentrating hormone neurones in the preoptic area of lactating mice.

Neurones expressing the melanin-concentrating hormone (MCH) can be found in the medial preoptic area (mPOA) and ventral aspects of the periventricular preoptic nucleus of rats by mid-to-late lactation and this expression disappears after weaning. The transitory expression of MCH in the preoptic area suggests a role for these neurones in the control of the end of lactation. However, the neurochemical identity of mPOA MCH neurones and the regulatory factors that control the transient MCH expression remain largely unknown, especially in the mouse. In the present study, we showed that mice also present the transitory expression of MCH in the mPOA at late lactation. mPOA MCH cells did not colocalise significantly with markers of GABAergic (VGAT), glutamatergic (VGLUT2 and VGLUT3) or dopaminergic (tyrosine hydroxylase) neurones. mPOA MCH cells also did not express Kiss1 or oxytocin. By contrast, approximately 70% and 90% of mPOA MCH neurones colocalised with oestrogen receptor α and prolactin-induced phosphorylated signal transducer and activator of transcription 5 (STAT5), respectively. Finally, we demonstrated that the number of MCH neurones in the mPOA is significantly higher in females during the first lactation, compared to mice on the second lactation or pregnant mice during the first lactation or brain-specific STAT5 knockout mice during the first lactation. In summary, our findings indicate that MCH neurones in the mPOA of lactating mice are sensitive to oestrogens and prolactin. Thus, mPOA MCH expression is possibly influenced by hormonal variations. Furthermore, the STAT5 signalling pathway is likely involved in the regulation of MCH expression in the mPOA of lactating mice.

Melanin-concentrating hormone peptidergic system: Comparative morphology between muroid species.

Melanin-concentrating hormone (MCH) is a conserved neuropeptide, predominantly located in the diencephalon of vertebrates, and associated with a wide range of functions. While functional studies have focused on the use of the traditional mouse laboratory model, critical gaps exist in our understanding of the morphology of the MCH system in this species. Even less is known about the nontraditional animal model Neotomodon alstoni (Mexican volcano mouse). A comparative morphological study among these rodents may, therefore, contribute to a better understanding of the evolution of the MCH peptidergic system. To this end, we employed diverse immunohistochemical protocols to identify key aspects of the MCH system, including its spatial relationship to another neurochemical population of the tuberal hypothalamus, the orexins. Three-dimensional (3D) reconstructions were also employed to convey a better sense of spatial distribution to these neurons. Our results show that the distribution of MCH neurons in all rodents studied follows a basic plan, but individual characteristics are found for each species, such as the preeminence of a periventricular group only in the rat, the lack of posterior groups in the mouse, and the extensive presence of MCH neurons in the anterior hypothalamic area of Neotomodon. Taken together, these data suggest a strong anatomical substrate for previously described functions of the MCH system, and that particular neurochemical and morphological features may have been determinant to species-specific phenotypes in rodent evolution.

Rouleaux formation of white blood cells and platelets in leukemia / Formação de rouleaux de glóbulos brancos e plaquetas em leucemia

The objective of this study was to measure the effects of glucose and salt level on white blood cells, red blood cells and platelets (PLTs) in the blood of a leukemic patient by using a white light microscope. Different concentrations of glucose and salt in the range of 0 mM to 500 mM were admixed in the blood sample to prepare blood smear. We revealed that shape of erythrocytes, leukocytes and platelets changes and form aggregates. Increasing concentrations of glucose cause to increases aggregation process of white blood cells, red blood cells and platelets. And the increasing concentration of sodium chloride causes to increase rouleaux formation and aggregation of platelets but dehydration due to increased sodium chloride concentration causes to break the aggregation of white blood cells. Comparison of CBC reports of these samples with and without analytes shows that total leukocyte count (TLC) decreases gradually towards normal ranges of leukocytes which is favorable in the treatment of leukemia but at the same time decreasing level of hemoglobin HGB, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and increasing level of red blood cell (RBCs) causes to reduce oxygen supply which is in favor of cancer growth and anemia. This work provides us the base for translation this in vitro study towards the in vivo case of blood microvasculature as a non-invasive methodology.

O objetivo deste estudo foi medir os efeitos da glicose e do nível de sal nos glóbulos brancos, glóbulos vermelhos e plaquetas (PLTs) no sangue de um paciente leucêmico usando um microscópio de luz branca. Foram misturadas diferentes concentrações de glicose e sal na gama de 0 mM a 500 mM na amostra de sangue para preparar esfregaço de sangue. Descrevemos que a forma dos eritrócitos, leucócitos e plaquetas muda e forma agregados. O aumento das concentrações de glicose aumenta o processo de agregação de glóbulos brancos, glóbulos vermelhos e plaquetas. E a crescente concentração de cloreto de sódio causa o aumento da formação de rouleaux e a agregação de plaquetas, mas a desidratação devido ao aumento da concentração de cloreto de sódio causa a quebra da agregação de glóbulos brancos. A comparação dos relatórios de CBC dessas amostras com e sem analitos mostra que a contagem total de leucócitos (TLC) diminui gradualmente para os intervalos normais de leucócitos, o que é favorável no tratamento da leucemia, mas ao mesmo tempo diminui o nível de hemoglobina HGB, hemoglobina corpuscular média (MCH ), a concentração média de hemoglobina corpuscular (MCHC) e o aumento do nível de glóbulos vermelhos (RBCs) reduz o suprimento de oxigênio, o que é a favor do crescimento do câncer e da anemia. Este trabalho fornece a base para a tradução deste estudo in vitro para o caso in vivo de microvasculatura de sangue como uma metodologia não-invasiva.

Does MCH play a role on establishment or maintenance of social hierarchy in Nile tilapia?

Body coloration has a fundamental role in animal communication by signaling sex, age, reproductive behavior, aggression, etc. Nile-tilapia exhibits dominance hierarchy and the dominants are paler than subordinates. During social interactions in these animals, these color changes occur rapidly, and normally the subordinates become dark. In teleosteans, from the great number of hormones and neurotransmitters involved in color changes, melanocyte hormone stimulates (α-MSH) and melanin concentrates hormone (MCH) are the most remarkable. The aim of this project was to investigate the role of MCH in the establishment of hierarchical dominance of the Nile-tilapia. We analyzed the effect of background coloration in the dominance hierarchy. It was then compared to the melanophore sensibility of dominants and subordinates' fishes to MCH; finally, it was checked if the social rank affects the number of these pigment cells in dominants and subordinated fishes. Fishes which have a social hierarchy established and adjusted individually to the background exhibits paler body coloration when a visual contact was possible, independently of previous social rank and background color. Probably, even recognizing each other, fishes could be defending their new territory. Melanophores of the subordinate fishes were more sensible to MCH than dominants. It suggests that dominants fishes, which are paler than subordinates, could be under a chronic effect of MCH, which could be due a desensitization of melanophores to this hormone. The opposite effect seems to be occurring on subordinate fishes. It was not observed a significant change in the number of melanophores when the fishes were exposed to a prolonged period of agonistic interaction. It is possible that the exposure time for this interaction might not have been sufficient to have any change in the number of these cells of dominants and subordinate fishes.

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.

The Melanin-Concentrating Hormone as an Integrative Peptide Driving Motivated Behaviors.

The melanin-concentrating hormone (MCH) is an important peptide implicated in the control of motivated behaviors. History, however, made this peptide first known for its participation in the control of skin pigmentation, from which its name derives. In addition to this peripheral role, MCH is strongly implicated in motivated behaviors, such as feeding, drinking, mating and, more recently, maternal behavior. It is suggested that MCH acts as an integrative peptide, converging sensory information and contributing to a general arousal of the organism. In this review, we will discuss the various aspects of energy homeostasis to which MCH has been associated to, focusing on the different inputs that feed the MCH peptidergic system with information regarding the homeostatic status of the organism and the exogenous sensory information that drives this system, as well as the outputs that allow MCH to act over a wide range of homeostatic and behavioral controls, highlighting the available morphological and hodological aspects that underlie these integrative actions. Besides the well-described role of MCH in feeding behavior, a prime example of hypothalamic-mediated integration, we will also examine those functions in which the participation of MCH has not yet been extensively characterized, including sexual, maternal, and defensive behaviors. We also evaluated the available data on the distribution of MCH and its function in the context of animals in their natural environment. Finally, we briefly comment on the evidence for MCH acting as a coordinator between different modalities of motivated behaviors, highlighting the most pressing open questions that are open for investigations and that could provide us with important insights about hypothalamic-dependent homeostatic integration.

Preterm delivery among first-time Mexico-born mothers: a binational population-based comparison of deliveries in California and Mexico.

BACKGROUND: While studies have attributed the favourable birth outcomes of Mexico-born mothers in the USA to a 'healthy immigrant effect' that confers protection to immigrants, a comparison of immigrants with the source population in Mexico has been lacking. We compared preterm delivery (PTD) rates of Mexico-born immigrants who delivered in California with Mexico-born women who delivered in Mexico (WIMX) and with a subgroup who delivered in the five top immigrant sending states in Mexico. METHODS: Using 2009 birth records, we selected all live-born singletons of primiparous WIMX (699 129) and immigrants in California (33 251). We examined the unadjusted and adjusted association between place of delivery and any PTD (<37 weeks gestation), including PTD subcategories (early, moderate, late), using relative risks (RR) and 95% CIs. Multivariate models controlled for demographic and health system characteristics. RESULTS: PTD rates were higher among immigrants in California (6.7%) than WIMX (5.8%) and compared to women in the sending states (5.5%). The unadjusted risk of any PTD (RR=1.17 (1.12 to 1.22)), early/moderate PTD (<34 weeks gestation; RR=1.27 (1.18 to 1.38)) and late PTD (34-36 weeks; RR=1.14 (1.08 to 1.19)) was higher for immigrants than for WIMX and remained higher when controlling for age, education and healthcare variables. Birth weight <1500 g was also higher among immigrants (RR=1.27 (1.14 to 1.44)). Similar patterns were observed when comparing women in the sending states. CONCLUSIONS: We found no evidence of a 'healthy immigrant effect'. Further research must assess the comparability of gestational-age data in Mexican and Californian birth certificates.

Melanin-Concentrating Hormone (MCH): Role in REM Sleep and Depression.

The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons of the lateral sector of the posterior hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, including areas such as the dorsal (DR) and median (MR) raphe nuclei, which are involved in the control of sleep and mood. Major Depression (MD) is a prevalent psychiatric disease diagnosed on the basis of symptomatic criteria such as sadness or melancholia, guilt, irritability, and anhedonia. A short REM sleep latency (i.e., the interval between sleep onset and the first REM sleep period), as well as an increase in the duration of REM sleep and the density of rapid-eye movements during this state, are considered important biological markers of depression. The fact that the greatest firing rate of MCHergic neurons occurs during REM sleep and that optogenetic stimulation of these neurons induces sleep, tends to indicate that MCH plays a critical role in the generation and maintenance of sleep, especially REM sleep. In addition, the acute microinjection of MCH into the DR promotes REM sleep, while immunoneutralization of this peptide within the DR decreases the time spent in this state. Moreover, microinjections of MCH into either the DR or MR promote a depressive-like behavior. In the DR, this effect is prevented by the systemic administration of antidepressant drugs (either fluoxetine or nortriptyline) and blocked by the intra-DR microinjection of a specific MCH receptor antagonist. Using electrophysiological and microdialysis techniques we demonstrated also that MCH decreases the activity of serotonergic DR neurons. Therefore, there are substantive experimental data suggesting that the MCHergic system plays a role in the control of REM sleep and, in addition, in the pathophysiology of depression. Consequently, in the present report, we summarize and evaluate the current data and hypotheses related to the role of MCH in REM sleep and MD.

Melanin-concentrating hormone in the medial preoptic area reduces active components of maternal behavior in rats.

Melanin-concentrating hormone (MCH) is an inhibitory neuropeptide mainly synthesized in neurons of the lateral hypothalamus and incerto-hypothalamic area of mammals that has been implicated in behavioral functions related to motivation. During lactation, this neuropeptide is also expressed in the medial preoptic area (mPOA), a key region of the maternal behavior circuitry. Notably, whereas MCH expression in the mPOA progressively increases during lactation, maternal behavior naturally declines, suggesting that elevated MCHergic activity in the mPOA inhibit maternal behavior in the late postpartum period. To explore this idea, we assessed the maternal behavior of early postpartum females following bilateral microinfusions of either MCH (50 and 100 ng/0.2 µl/side) or the same volume of vehicle into the mPOA. As expected, females receiving 100 ng MCH into the mPOA exhibited significant deficits in the active components of maternal behavior, including retrieving and nest building. In contrast, nursing, as well as other behaviors, including locomotor activity, exploration, and anxiety-like behavior, were not affected by intra-mPOA MCH infusion. The present results, together with previous findings showing elevated expression of this neuropeptide toward the end of the postpartum period, suggest that modulation of mPOA function by MCH may contribute to the weaning of maternal responsiveness characteristic of the late postpartum period.