scholarly journals Paternally expressed gene 3 (Pw1/Peg3) promotes sexual dimorphism in metabolism and behavior

PLoS Genetics ◽  
2022 ◽  
Vol 18 (1) ◽  
pp. e1010003
Author(s):  
Karo Tanaka ◽  
Vanessa Besson ◽  
Manon Rivagorda ◽  
Franck Oury ◽  
Giovanna Marazzi ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Sex Steroid ◽  
Steroid Dependent ◽  
Insulin Dependent ◽  
Dependent Growth ◽  
Male Specific ◽  
And Behavior ◽  
The Brain ◽  
Deficient Mice

The paternally expressed gene 3 (Pw1/Peg3) is a mammalian-specific parentally imprinted gene expressed in stem/progenitor cells of the brain and endocrine tissues. Here, we compared phenotypic characteristics in Pw1/Peg3 deficient male and female mice. Our findings indicate that Pw1/Peg3 is a key player for the determination of sexual dimorphism in metabolism and behavior. Mice carrying a paternally inherited Pw1/Peg3 mutant allele manifested postnatal deficits in GH/IGF dependent growth before weaning, sex steroid dependent masculinization during puberty, and insulin dependent fat accumulation in adulthood. As a result, Pw1/Peg3 deficient mice develop a sex-dependent global shift of body metabolism towards accelerated adiposity, diabetic-like insulin resistance, and fatty liver. Furthermore, Pw1/Peg3 deficient males displayed reduced social dominance and competitiveness concomitant with alterations in the vasopressinergic architecture in the brain. This study demonstrates that Pw1/Peg3 provides an epigenetic context that promotes male-specific characteristics through sex steroid pathways during postnatal development.

scholarly journals Male Reproductive Defects Caused by Puromycin-Sensitive Aminopeptidase Deficiency in Mice

2001 ◽  
Vol 15 (6) ◽  
pp. 960-971 ◽  
Author(s):  
Tomoharu Osada ◽  
Gen Watanabe ◽  
Shunzo Kondo ◽  
Masashi Toyoda ◽  
Yoshiyuki Sakaki ◽  
...  
Keyword(s):  
Reproductive Performance ◽  
Sertoli Cells ◽  
Steroid Receptors ◽  
Copulatory Behavior ◽  
Sex Steroid ◽  
Signal Pathways ◽  
Biological Processes ◽  
The Brain ◽  
Principal Elements ◽  
Deficient Mice

Abstract Male reproductive performance is composed of two principal elements, copulation and spermatogenesis. A wealth of literature has described the intricate web of endocrine events underlying these biological processes. In the present study we show that puromycin-sensitive aminopeptidase (Psa)-deficient mice are infertile, lack copulatory behavior, and have impaired spermatogenesis. The reproductive deficits of the mutants are not restored by androgen administration, although no aberrant localization of the sex steroid receptors was detectable in their brains and testes. Considering the strong expression of the Psa gene in the brain and Sertoli cells and the degenerative morphology of Sertoli cells in Psa-deficient mice, Psa may participate in testosterone-mediated reproductive signal pathways in the brain and testis.

scholarly journals Sexual Dimorphism of Growth Hormone in the Hypothalamus: Regulation by Estradiol

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1898-1907 ◽  
Author(s):  
Melisande L. Addison ◽  
Emilie F. Rissman
Keyword(s):  
Sexual Dimorphism ◽  
Arcuate Nucleus ◽  
Estrogen Receptor Α ◽  
Brain Regions ◽  
Brain Cell ◽  
Pituitary Hormone ◽  
Sexual Dimorphisms ◽  
Anterior Pituitary Hormone ◽  
And Behavior ◽  
The Brain

GH is best known as an anterior pituitary hormone fundamental in regulating growth, differentiation, and metabolism. GH peptide and mRNA are also present in brain, in which their functions are less well known. Here we describe the distribution of GH neurons and fibers and sex differences in Gh mRNA in adult mouse brain. Cell bodies exhibiting GH immunoreactivity are distributed in many brain regions, particularly in the hypothalamus in which retrograde labeling suggests that some of these cells project to the median eminence. To determine whether Gh mRNA is sexual dimorphic, we carried out quantitative RT-PCR on microdissected brain nuclei. Ovary-intact mice had elevated Gh mRNA in the arcuate nucleus and medial preoptic area (MPOA) compared with gonad-intact males. In males, castration increased Gh mRNA in the MPOA, whereas ovariectomy decreased Gh mRNA in both regions. When gonadectomized adults of both sexes were treated with estradiol Gh mRNA increased in females but had no effect in castrated males. Tamoxifen was able to blunt the rise in Gh mRNA in response to estradiol in females. In addition, we found that estrogen receptor-α is coexpressed in GH neurons in the MPOA and arcuate nucleus. In summary, the findings reveal sexual dimorphisms in Gh gene expression in areas of the brain associated with reproduction and behavior. Interestingly, estradiol enhances Gh mRNA in females only, suggesting that multiple factors orchestrate this sexual dimorphism.

Review of Self-regulation of the Brain and Behavior.

1985 ◽  
Vol 30 (12) ◽  
pp. 999-999
Author(s):  
Gerald S. Wasserman
Keyword(s):  
Self Regulation ◽  
Brain And Behavior ◽  
And Behavior ◽  
The Brain

LC-MS/MS Method Development and Validation for the Determination of Ilexsaponin A1 and Its Application in Intestinal Bacterial Metabolic Study

2020 ◽  
Vol 16 (6) ◽  
pp. 774-781
Author(s):  
Liang Wu ◽  
An Kang ◽  
Yujie Lin ◽  
Chenxiao Shan ◽  
Zhu Zhou ◽  
...  
Keyword(s):  
Method Development ◽  
Ischemia Reperfusion ◽  
Scientific Evidence ◽  
Potential Effect ◽  
Bacterial Strains ◽  
Metabolic Potential ◽  
Bifidobacterium Adolescentis ◽  
Metabolic Behavior ◽  
And Behavior

Background: Ilexsaponin A1, one of the most representative triterpene saponin components in the roots of I. pubescens, showed its effects in anticoagulation and antithrombosis, attenuating ischemia-reperfusion-induced myocardial, angiogenesis and inhibiting phosphodiesterase. Objective: Reveal the key intestinal bacterial strains responsible for ilexsaponin A1 metabolism, and clarify their metabolic behavior. Methods: An accurate and sensitive LC-MS/MS method for the determination of “ilexsaponin A1 in General Anaerobic Medium (GAM) broth” was established and systematically validated. Then it was applied to screen and study the metabolic potential of the intestinal bacterial strains in an anaerobic incubation system. Results: Quantitation of ilexsaponin A1 could be performed within an analytical run time of 14.5 min, in the linear range of 2 - 2000 ng/ml. Enterobacter sakazakii, Bifidobacterium breve, Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Bifidobacterium angulatum were identified to have a potential effect to metabolize ilexsaponin A1 to different extents; and further bacterial metabolic studies were performed to clarify their metabolic capacity and behavior. Conclusion: This paper contributes to a better understanding of the intestinal bacterial metabolism of ilexsaponin A1 and provides scientific evidence for its clinical application. Additionally, the importance of intestinal bacterial strains in the disposition of natural products was also highlighted.

Simultaneous Determination of Imatinib and N-Desmethyl Imatinib in Rat Plasma and Tissues Using LC-MS/MS

2019 ◽  
Vol 15 (2) ◽  
pp. 121-129
Author(s):  
Zhi Rao ◽  
Bo-xia Li ◽  
Yong-Wen Jin ◽  
Wen-Kou ◽  
Yan-rong Ma ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Oral Administration ◽  
Parent Drug ◽  
Gradient Elution ◽  
Biological Tissues ◽  
Rat Plasma ◽  
Running Water ◽  
Liver And Kidney ◽  
The Brain

Background: Imatinib (IM) is a chemotherapy medication metabolized by CYP3A4 to Ndesmethyl imatinib (NDI), which shows similar pharmacologic activity to the parent drug. Although methods for determination of IM and/or NDI have been developed extensively, only few observations have been addressed to simultaneously determine IM and NDI in biological tissues such as liver, kidney, heart, brain and bone marrow. Methods: A validated LC-MS/MS method was developed for the quantitative determination of imatinib (IM) and N-desmethyl imatinib (NDI) from rat plasma, bone marrow, brain, heart, liver and kidney. The plasma samples were prepared by protein precipitation, and then the separation of the analytes was achieved using an Agilent Zorbax Eclipse Plus C18 column (4.6 × 100 mm, 3.5 µm) with gradient elution running water (A) and methanol (B). Mass spectrometric detection was achieved by a triplequadrupole mass spectrometer equipped with an electrospray source interface in positive ionization mode. Results: This method was used to investigate the pharmacokinetics and the tissue distributions in rats following oral administration of 25 mg/kg of IM. The pharmacokinetic profiles suggested that IM and NDI are disappeared faster in rats than human, and the tissue distribution results showed that IM and NDI had good tissue penetration and distribution, except for the brain. This is the first report about the large penetrations of IM and NDI in rat bone marrow. Conclusion: The method demonstrated good sensitivity, accuracy, precision and recovery in assays of IM and NDI in rats. The described assay was successfully applied for the evaluation of pharmacokinetics and distribution in the brain, heart, liver, kidney and bone marrow of IM and NDI after a single oral administration of IM to rats.

CCR5 deficiency decreases susceptibility to experimental cerebral malaria

Blood ◽  
2003 ◽  
Vol 101 (11) ◽  
pp. 4253-4259 ◽  
Author(s):  
Elodie Belnoue ◽  
Michèle Kayibanda ◽  
Jean-Christophe Deschemin ◽  
Mireille Viguier ◽  
Matthias Mack ◽  
...  
Keyword(s):  
T Cells ◽  
Cerebral Malaria ◽  
Cd8 T Cells ◽  
Cytokine Production ◽  
Wild Type ◽  
Experimental Cerebral Malaria ◽  
Pathologic Features ◽  
Th1 Cytokine ◽  
The Brain ◽  
Deficient Mice

Abstract Infection of susceptible mouse strains with Plasmodium berghei ANKA (PbA) is a valuable experimental model of cerebral malaria (CM). Two major pathologic features of CM are the intravascular sequestration of infected erythrocytes and leukocytes inside brain microvessels. We have recently shown that only the CD8+ T-cell subset of these brain-sequestered leukocytes is critical for progression to CM. Chemokine receptor–5 (CCR5) is an important regulator of leukocyte trafficking in the brain in response to fungal and viral infection. Therefore, we investigated whether CCR5 plays a role in the pathogenesis of experimental CM. Approximately 70% to 85% of wild-type and CCR5+/- mice infected with PbA developed CM, whereas only about 20% of PbA-infected CCR5-deficient mice exhibited the characteristic neurologic signs of CM. The brains of wild-type mice with CM showed significant increases in CCR5+ leukocytes, particularly CCR5+ CD8+ T cells, as well as increases in T-helper 1 (Th1) cytokine production. The few PbA-infected CCR5-deficient mice that developed CM exhibited a similar increase in CD8+ T cells. Significant leukocyte accumulation in the brain and Th1 cytokine production did not occur in PbA-infected CCR5-deficient mice that did not develop CM. Moreover, experiments using bone marrow (BM)–chimeric mice showed that a reduced but significant proportion of deficient mice grafted with CCR5+ BM develop CM, indicating that CCR5 expression on a radiation-resistant brain cell population is necessary for CM to occur. Taken together, these results suggest that CCR5 is an important factor in the development of experimental CM.

Individual Uniqueness in the Neonatal Functional Connectome

2021 ◽  
Author(s):  
Qiushi Wang ◽  
Yuehua Xu ◽  
Tengda Zhao ◽  
Zhilei Xu ◽  
Yong He ◽  
...  
Keyword(s):  
Individual Differences ◽  
Individual Identification ◽  
Imaging Data ◽  
Functional Connectome ◽  
Middle Range ◽  
Human Connectome Project ◽  
The Individual ◽  
And Behavior ◽  
Identification Analysis ◽  
The Brain

Abstract The functional connectome is highly distinctive in adults and adolescents, underlying individual differences in cognition and behavior. However, it remains unknown whether the individual uniqueness of the functional connectome is present in neonates, who are far from mature. Here, we utilized the multiband resting-state functional magnetic resonance imaging data of 40 healthy neonates from the Developing Human Connectome Project and a split-half analysis approach to characterize the uniqueness of the functional connectome in the neonatal brain. Through functional connectome-based individual identification analysis, we found that all the neonates were correctly identified, with the most discriminative regions predominantly confined to the higher-order cortices (e.g., prefrontal and parietal regions). The connectivities with the highest contributions to individual uniqueness were primarily located between different functional systems, and the short- (0–30 mm) and middle-range (30–60 mm) connectivities were more distinctive than the long-range (>60 mm) connectivities. Interestingly, we found that functional data with a scanning length longer than 3.5 min were able to capture the individual uniqueness in the functional connectome. Our results highlight that individual uniqueness is present in the functional connectome of neonates and provide insights into the brain mechanisms underlying individual differences in cognition and behavior later in life.

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