Increase in serum prolactin levels in females improves the performance of spatial learning by promoting changes in the circuital dynamics of the hippocampus.

Beyond the direct physiological functions associated with motherhood in mammals, previous studies have suggested the potential role of prolactin (Prl) in distinct brain processes such as neuroprotection, neurogenesis, and stress responses. However, the cognitive influence of Prl remains unclear, particularly regarding the mechanisms of acquisition, consolidation and retrieval of information in the brain. Using chronic implanted electrodes in freely moving female mice combined with behavioral tests, we investigated the rhythmic activity changes induced by Prl in a model of hippocampus-dependent learning and memory. Our results show that Prl improves the learning of a spatial memory task in the acquisition stage. The main variations at the circuitry level were in the theta frequency band (4-8 Hz and 8-12 Hz), marked by a faster change in oscillatory activity with no modifications to higher frequencies. These results show that Prl plays a significant role in the acquisition of information during learning of a spatial memory task, suggesting that an increase in Prl levels may induce changes in circuital network plasticity.

Prolactin enhances hippocampal synaptic plasticity in female mice of reproductive age.

Dynamic signaling between the endocrine system (ES) and the nervous system (NS) is essential for brain and body homeostasis. In particular, reciprocal interaction occurs during pregnancy and motherhood that may involve changes in some brain plasticity processes. Prolactin (PRL), a hormone with pleiotropic effects on the NS, promotes maternal behavior and has been linked to modifications in brain circuits during motherhood; however, it is unclear whether PRL may regulate synaptic plasticity. Therefore, the main aim of the present work was to determine the cellular and molecular mechanisms triggered by PRL that regulate synaptic plasticity in the hippocampus. By analyzing extracellular recordings in CA3-CA1 synapses of hippocampal slices, we report that PRL modifies short and long-term synaptic plasticity in female mice of reproductive age, but not in sexually immature females or adult males. This effect is carried out through mechanisms that include participation of GABAA receptors and activation of the JAK2-mediated signaling pathway. These findings show for the first time how PRL enhances the synaptic strength in hippocampal circuits and that this effect is sexually dimorphic, which would influence complex brain processes in physiological conditions like pregnancy and lactation.

The expansion of adult stem/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy.

Extensive evidence has revealed variations in the number of hormone-producing cells in the pituitary gland, which occur under physiological conditions such as gestation and lactancy. It has been proposed that new hormone-producing cells differentiate from stem cells. However, exactly how and when this takes place is not clear. In this work, we used immunoelectron microscopy to identify adult pituitary stem/progenitor cells (SC/P) localized in the marginal zone (MZ), and additionally, we detected GFRa2-, Sox2-, and Sox9-positive cells in the adenoparenchyma (AP) by fluorescence microscopy. Then, we evaluated fluctuations of SC/P mRNA and protein level markers in MZ and AP during gestation and lactancy. An upregulation in stemness markers was shown at term of gestation (AT) in MZ, whereas there were more progenitor cell markers in the middle of gestation and active lactancy. Concerning committed cell markers, we detected a rise in AP at beginning of lactancy (d1L). We performed a BrdU uptake analysis in MZ and AP cells. The highest level of BrdU uptake was observed in MZ AT cells, whereas in AP this was detected in d1L, followed by a decrease in both the MZ and AP. Finally, we detected double immunostaining for BrdU-GFRa2 in MZ AT cells and BrdU-Sox9 in the AP d1L cells. Taken together, we hypothesize that the expansion of the SC/P niche took place mainly in MZ from pituitary rats in AT and d1L. These results suggest that the SC niche actively participates in pituitary plasticity during these reproductive states, contributing to the origin of hormone cell populations.

Characterization of paneth cells in alpacas (Vicugna pacos, Mammalia, Camelidae).

Paneth cells are secretory epithelial cells of the innate immune system of the intestine of several mammals, including alpacas. Little is known about the latter; thus, in the present study we described the morphology and histochemical characteristics of Paneth cells in healthy fetuses, and young and adult alpacas. For this purpose, samples of duodenum, jejunum and ileum were taken from 6 fetuses at different days of pregnancy (between days 221-330), 66 offsprings (between 0 and 45-days-old) and 5 adult alpacas (>2-years-old). Samples were fixed in 10% buffered formalin and processed for histological and morphometrical analysis using HE and Masson Trichomics technique. Immunohistochemistry was used to identify Paneth cells using anti-lysozyme antibody. In addition, the lectinhistochemichal binding-pattern of Paneth cells granules was evaluated. Lyzozyme was immunohistochemically detected in the granules of Paneth cells from day 283 of pregnancy in all the small intestinal sections of the studied fetuses. In newborn alpacas Paneth cells were initially found in the duodenum, but the following days (days 18-21 after birth) they were also found in the ileum. Their size gradually increased after birth, but then no significant differences were found. In adult alpacas the number was lower than offsprings. We suggest that Paneth cells early differentiate in the small intestine of alpacas, and the increase in their number during the first two weeks of life strongly support their possible involvement in the intestinal defensive functions against the enteric diseases that occur during the lactancy stage.

ß-defensin-2 in breast milk displays a broad antimicrobial activity against pathogenic bacteria / ß-defensina 2 no leite materno mostra uma ampla atividade antimicrobiana contra bactérias patogênicas

OBJECTIVE: To describe the antimicrobial activity of ß-defensin-2 produced in the mammary gland and secreted in human breast milk. METHODS: The peptide production was performed by DNA cloning. ß-defensin-2 levels were quantified in 61 colostrum samples and 39 mature milk samples from healthy donors, by an indirect enzyme-linked immunosorbent assay (ELISA). Using halo inhibition assay, this study assessed activity against seven clinical isolates from diarrheal feces of children between 0 and 2 years of age. The activity of ß-defensin-2 against three opportunistic pathogens that can cause nosocomial infections was determined by microdilution test. RESULTS: The peptide levels were higher in colostrum (n = 61) than in mature milk samples (n = 39), as follows: median and range, 8.52 (2.6-16.3) µg/ml versus 0.97 (0.22-3.78), p < 0.0001; Mann-Whitney test. The recombinant peptide obtained showed high antimicrobial activity against a broad range of pathogenic bacteria. Its antibacterial activity was demonstrated in a disk containing between 1-4 µg, which produced inhibition zones ranging from 18 to 30 mm against three isolates of Salmonella spp. and four of E. coli. ß-defensin-2 showed minimum inhibitory concentrations (MICs) of 0.25 µg/mL and 0.5 µg/mL for S. marcescen and P. aeruginosa, respectively, while a higher MIC (4 µg/mL) was obtained against an isolated of multidrug-resistant strain of A. baumannii. CONCLUSIONS: To the authors' knowledge, this study is the first to report ß-defensin-2 levels in Latin American women. The production and the activity of ß-defensin-2 in breast milk prove its importance as a defense molecule for intestinal health in pediatric patients. .

OBJETIVO: Descrever a atividade antimicrobiana da defensina-beta 2 na glândula mamária e secretada no leite materno humano. MÉTODOS: A produção de peptídeos foi realizada por clonagem de DNA. Os níveis de defensina-beta 2 foram quantificados em 61 amostras de colostro e 39 de leite maduro de doadoras saudáveis pelo teste ELISA indireto. Por um ensaio de halo de inibição, avaliamos a atividade contra sete isolados clínicos diarreicos de crianças entre 0 e 2 anos. A atividade da defensina 2 contra três patógenos oportunistas que podem causar infecções nosocomiais foi determinada pelo teste de microdiluição. RESULTADOS: Os níveis de peptídeos estavam significativamente maiores nas amostras de colostro (n = 61) que de leite maduro (n = 39), como segue: 8,52 (2,6-16,3 µg/mL) mediana e faixa em comparação a 0,97 (0,22-3,78), p < 0,0001; teste de Mann-Whitney. O peptídeo recombinante foi obtido da alta atividade antimicrobiana demonstrada contra uma ampla gama de bactérias patogênicas. Sua atividade antibacteriana foi demonstrada em um disco contendo entre 1-4 µg, que produziu zonas de inibição entre 18 e 30 mm contra três isolados de Salmonella spp. e quatro de E. coli. A defensina-beta 2 demonstrou concentrações inibitórias mínimas (CIMs) de 0,25 µg/mL e 0,5 µg/mL para S. marcescen and P. aeruginosa, ao passo que uma CIM maior (4 µg/mL) foi obtida contra um isolado de cepa multirresistente de A. baumannii. CONCLUSÕES: Até onde sabemos, este estudo é o primeiro a relatar níveis de defensina em mulheres da América Latina. A produção e a atividade da defensina 2 no leite materno comprovam sua importância como uma molécula de defesa para a saúde intestinal em pacientes pediátricos. .

ß-defensin-2 in breast milk displays a broad antimicrobial activity against pathogenic bacteria.

OBJECTIVE: To describe the antimicrobial activity of ß-defensin-2 produced in the mammary gland and secreted in human breast milk. METHODS: The peptide production was performed by DNA cloning. ß-defensin-2 levels were quantified in 61 colostrum samples and 39 mature milk samples from healthy donors, by an indirect enzyme-linked immunosorbent assay (ELISA). Using halo inhibition assay, this study assessed activity against seven clinical isolates from diarrheal feces of children between 0 and 2 years of age. The activity of ß-defensin-2 against three opportunistic pathogens that can cause nosocomial infections was determined by microdilution test. RESULTS: The peptide levels were higher in colostrum (n=61) than in mature milk samples (n=39), as follows: median and range, 8.52 (2.6-16.3) µg/ml versus 0.97 (0.22-3.78), p<0.0001; Mann-Whitney test. The recombinant peptide obtained showed high antimicrobial activity against a broad range of pathogenic bacteria. Its antibacterial activity was demonstrated in a disk containing between 1-4 µg, which produced inhibition zones ranging from 18 to 30 mm against three isolates of Salmonella spp. and four of E. coli. ß-defensin-2 showed minimum inhibitory concentrations (MICs) of 0.25 µg/mL and 0.5 µg/mL for S. marcescen and P. aeruginosa, respectively, while a higher MIC (4 µg/mL) was obtained against an isolated of multidrug-resistant strain of A. baumannii. CONCLUSIONS: To the authors' knowledge, this study is the first to report ß-defensin-2 levels in Latin American women. The production and the activity of ß-defensin-2 in breast milk prove its importance as a defense molecule for intestinal health in pediatric patients.

Role of leptin and its receptor on bovine mammary gland / Papel de la leptina y su receptor en la glándula mamaria bovina / Papel da leptina e seu receptor na glândula mamária bovina

Leptin is a hormone-like protein involved in physiological processes related to the regulation of energy metabolism, reproduction, immunity, cancer, breastfeeding, among others. Leptin receptor is expressed in almost all tissues and generates six isoforms from a single mRNA. The predominant isoform in bovine mammary gland is the Ob-Rb, which triggers a signaling cascade through JAK-STAT molecules to induce proliferation, differentiation and apoptosis, according to the female reproductive stage. In small ruminants, such as sheep and goats, leptin and its receptor levels vary widely, being high at the beginning of pregnancy, tending to fall in mid-gestation, and remaining low until the end of lactation. An expression pattern of leptin receptor has not yet been established for the various reproductive stages in bovine mammary gland. Such study is considered important and necessary to understand the effect of leptin via its receptor in mammary gland, especially during lactation when the gland undergoes tissue remodeling to sustain high milk production. This review presents a hypothesis about the signaling pathway triggered by leptin receptor in the mammary gland during bovine lactation.

La leptina es una hormona proteínica que participa en procesos fisiológicos relacionados con la regulación del metabolismo energético, reproducción, inmunidad, cáncer, lactancia, entre otros. Su receptor se expresa en casi la totalidad de los tejidos, presentando seis isoformas a partir de un mismo ARNm. La isoforma predominante en la glándula mamaria bovina es la Ob-Rb, a través de la cual se puede desencadenar una cascada de señalización por medio de las moléculas JAK-STAT, para inducir proliferación, diferenciación y apoptosis celular de acuerdo al estadio reproductivo de la hembra. En pequeños rumiantes, tales como ovejas y cabras, los niveles de leptina y su receptor varían considerablemente durante la preñez y lactancia: son altos al inicio de la gestación, tienden a descender hasta la mitad de esta etapa y permanecen bajos hasta la finalización de la lactancia. En la glándula mamaria de bovinos aún no se ha establecido un patrón de expresión de los receptores durante diferentes etapas reproductivas, estudio que se considera importante y necesario para comprender el efecto de la leptina sobre su receptor en glándula mamaria, especialmente durante la lactancia, período durante el cual sufre una remodelación celular del tejido glandular para sostener una alta producción láctea. En la presente revisión se plantea una hipótesis de cómo podría ser la vía de señalización desencadenada por el receptor de leptina en la glándula mamaria durante la lactancia.

A leptina é um hormônio protéico envolvido em processos fisiológicos relacionados com a regulação do metabolismo energético, reprodução, imunidade, câncer, lactação, entre outros. Seu receptor é expresso em quase todos os tecidos e apresenta seis isoformas a partir do mesmo mRNA. A isoforma predominante na glândula mamária bovina é a Ob-Rb, através da qual é desencadeada uma cascata de sinalização através das moléculas JAK-STAT para induzir a diferenciação, proliferação e apoptose de acordo com o estágio reprodutivo da fêmea. Em pequenos ruminantes, como ovinos e caprinos, os níveis de leptina e seu receptor variam consideravelmente durante a gravidez e a lactação. São altos no início da gravidez, tendem a cair na metade dessa fase e permanecem baixos até o final da lactação. Ainda não foi estabelecido um padrão de expressão do receptor de leptina na glândula mamária de bovinos durante diferentes estágios reprodutivos. O estudo deste tema é importante e necessário para entender o efeito da leptina sobre o seu receptor na glândula mamária, especialmente durante a lactação, periodo no qual a glândula mamária sofre remodelação do tecido glandular com a finalidade de sustentar a alta produção de leite. A presente revisão apresenta uma hipótese sobre a via de sinalização que é desencadeada pelo receptor da leptina na glândula mamária durante a lactação.