scholarly journals Deletion of Rptor in pre‐osteoblasts reveals a role for the mTORC1 complex in dietary‐induced changes to bone mass and glucose homeostasis in female mice

JBMR Plus ◽  
2021 ◽  
Author(s):  
Pawanrat Tangseefa ◽  
Sally K. Martin ◽  
Agnieszka Arthur ◽  
Vasilios Panagopoulos ◽  
Amanda J. Page ◽  
...  
Keyword(s):  
Bone Mass ◽  
Glucose Homeostasis ◽  
Female Mice ◽  
Induced Changes

scholarly journals Female Mice Lacking Estrogen Receptor-Alpha in Osteoblasts Have Compromised Bone Mass and Strength

2014 ◽  
Vol 29 (2) ◽  
pp. 370-379 ◽  
Author(s):  
Katherine M Melville ◽  
Natalie H Kelly ◽  
Sohaib A Khan ◽  
John C Schimenti ◽  
F Patrick Ross ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Mass ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha ◽  
Female Mice

scholarly journals Mutation of the Galectin-3 Glycan Binding Domain (Lgals3-R200S) Enhances Cortical Bone Expansion in Male and Trabecular Bone Mass in Female Mice

2020 ◽  
Author(s):  
Kevin A. Maupin ◽  
Daniel Dick ◽  
VARI Vivarium ◽  
Transgenics Core ◽  
Bart O. Williams
Keyword(s):  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Mutant Mice ◽  
Slight Variation ◽  
Female Mice ◽  
Bone Phenotype ◽  
Bone Expansion ◽  
Galectin 3 ◽  
Trabecular Bone Mass

AbstractThe study of galectin-3 is complicated by its ability to function both intracellularly and extracellularly. While the mechanism of galectin-3 secretion is unclear, studies have shown that the mutation of a highly conserved arginine to a serine in human galectin-3 (LGALS3-R186S) blocks glycan binding and secretion. To gain insight into the roles of extracellular and intracellular functions of galectin-3, we generated mice with the equivalent mutation (Lgals3-R200S) using CRISPR/Cas9-directed homologous recombination. Consistent with a reduction in galectin-3 secretion, we observed significantly reduced galectin-3 protein levels in the plasma of heterozygous and homozygous mutant mice. We observed a similar increased bone mass phenotype in Lgals3-R200S mutant mice at 36 weeks as we previously observed in Lgals3-KO mice with slight variation. Like Lgals3-KO mice, Lgals3-R200S females, but not males, had significantly increased trabecular bone mass. However, only male Lgals3-R200S mice showed increased cortical bone expansion, which we had previously observed in both male and female Lgals3-KO mice and only in female mice using a separate Lgals3 null allele (Lgals3). These results suggest that the trabecular bone phenotype of Lgals3-KO mice was driven primarily by loss of extracellular galectin-3. However, the cortical bone phenotype of Lgals3-KO mice may have also been influenced by loss of intracellular galectin-3. Future analyses of these mice will aid in identifying the cellular and molecular mechanisms that contribute to the Lgals3-deficient bone phenotype as well as aid in distinguishing the extracellular vs. intracellular roles of galectin-3 in various signaling pathways.

scholarly journals Analgesic effects of optogenetic inhibition of basolateral amygdala inputs into the prefrontal cortex in nerve injured female mice

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Vinicius M. Gadotti ◽  
Zizhen Zhang ◽  
Junting Huang ◽  
Gerald W. Zamponi
Keyword(s):  
Prefrontal Cortex ◽  
Nerve Injury ◽  
Basolateral Amygdala ◽  
Thermal Hyperalgesia ◽  
Pyramidal Cells ◽  
Male Mice ◽  
Female Mice ◽  
Analgesic Effects ◽  
Induced Changes ◽  
Thermal Stimuli

AbstractPeripheral nerve injury can lead to remodeling of brain circuits, and this can cause chronification of pain. We have recently reported that male mice subjected to spared injury of the sciatic nerve undergo changes in the function of the medial prefrontal cortex (mPFC) that culminate in reduced output of layer 5 pyramidal cells. More recently, we have shown that this is mediated by alterations in synaptic inputs from the basolateral amygdala (BLA) into GABAergic interneurons in the mPFC. Optogenetic inhibition of these inputs reversed mechanical allodynia and thermal hyperalgesia in male mice. It is known that the processing of pain signals can exhibit marked sex differences. We therefore tested whether the dysregulation of BLA to mPFC signaling is equally altered in female mice. Injection of AAV-Arch3.0 constructs into the BLA followed by implantation of a fiberoptic cannula into the mPFC in sham and SNI operated female mice was carried out, and pain behavioral responses were measured in response to yellow light mediated activation of this inhibitory opsin. Our data reveal that Arch3.0 activation leads to a marked increase in paw withdrawal thresholds and latencies in response to mechanical and thermal stimuli, respectively. However, we did not observe nerve injury-induced changes in mPFC layer 5 pyramidal cell output in female mice. Hence, the observed light-induced analgesic effects may be due to compensation for dysregulated neuronal circuits downstream of the mPFC.

scholarly journals Sclerostin Antibody–Induced Changes in Bone Mass Are Site Specific in Developing Crania

2019 ◽  
Vol 34 (12) ◽  
pp. 2301-2310 ◽  
Author(s):  
Amanda L Scheiber ◽  
David K Barton ◽  
Basma M Khoury ◽  
Joan C Marini ◽  
Donald L Swiderski ◽  
...  
Keyword(s):  
Bone Mass ◽  
Site Specific ◽  
Induced Changes ◽  
Sclerostin Antibody

scholarly journals SAT-657 The Gut Microbiome Regulates Host Glucose Homeostasis via Peripheral Serotonin

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Damien Keating
Keyword(s):  
Gut Microbiota ◽  
Glucose Homeostasis ◽  
Gut Microbiome ◽  
Microbiota Composition ◽  
Serotonin Synthesis ◽  
Pharmacological Inhibition ◽  
Genetic Deletion ◽  
Underlying Mechanisms ◽  
Induced Changes ◽  
Host Metabolism

Abstract The gut microbiome is an established regulator of aspects of host metabolism, such as glucose handling. Despite the known impacts of the gut microbiota on host glucose homeostasis, the underlying mechanisms are unknown. The gut microbiome is also a potent mediator of gut-derived serotonin synthesis, and this peripheral source of serotonin is itself a regulator of glucose homeostasis. Here, we determined whether the gut microbiome influences glucose homeostasis through effects on gut-derived serotonin. Using both pharmacological inhibition and genetic deletion of gut-derived serotonin synthesis, we find [1] that the improvements in host glucose handling caused by antibiotic-induced changes in microbiota composition are dependent on the synthesis of peripheral serotonin. [1] The gut microbiome regulates host glucose homeostasis via peripheral serotonin. Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):19802-19804. Martin AM, Yabut JM, Choo JM, Page AJ, Sun EW, Jessup CF, Wesselingh SL, Khan WI, Rogers GB, Steinberg GR, Keating DJ.

Sign in / Sign up

Export Citation Format

Share Document