Female Mice
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2021 ◽  
Vol 25 (6) ◽  
pp. 575-583
Author(s):  
Hyun-Jung Kim ◽  
Chang Mo Moon ◽  
Jihee Lee Kang ◽  
Eun-Mi Park

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew R. Evrard ◽  
Michael Li ◽  
Hui Shen ◽  
Sheryl S. Smith

AbstractAnxiety is increasingly reported, especially in adolescent females. The etiology is largely unknown, which limits effective treatment. Layer 5 prelimbic cortex (L5PL) increases anxiety responses but undergoes adolescent synaptic pruning, raising the question of the impact of pruning on anxiety. Here we show that preventing L5PL pruning increases anxiety in response to an aversive event in adolescent and adult female mice. Spine density of Golgi-stained neurons decreased ~ 63% from puberty (~ PND35, vaginal opening) to post-puberty (PND56, P < 0.0001). Expression of α4βδ GABAA receptors (GABARs) transiently increased tenfold in L5PL at puberty (P < 0.00001), but decreased post-pubertally. Both global and local knockdown of these receptors during puberty prevented pruning, increasing spine density post-pubertally (P < 0.0001), an effect reversed by blocking NMDA receptors (NMDARs). Pubertal expression of the NMDAR-dependent spine protein kalirin7 decreased (50%, P < 0.0001), an effect prevented by α4 knock-out, suggesting that α4βδ-induced reductions in kalirin7 underlie pruning. Increased spine density due to local α4 knockdown at puberty decreased open arm time on the elevated plus maze post-pubertally (62%, P < 0.0001) in response to an aversive stimulus, suggesting that increases in L5PL synapses increase anxiety responses. These findings suggest that prelimbic synaptic pruning is necessary to limit anxiety in adulthood and may suggest novel therapies.


2021 ◽  
Vol 11 (11) ◽  
pp. 1398
Author(s):  
Anlong Jiang ◽  
Le Wang ◽  
Justin Y. D. Lu ◽  
Amy Freeman ◽  
Charlie Campbell ◽  
...  

Fragile X syndrome (FXS) is an X-chromosome-linked dominant genetic disorder that causes a variable degree of cognitive dysfunction and developmental disability. Current treatment is symptomatic and no existing medications target the specific cause of FXS. As with other X-linked disorders, FXS manifests differently in males and females, including abnormalities in the dopamine system that are also seen in Fmr1-knockout (KO) mice. We investigated sex differences in dopamine signaling in Fmr1-KO mice in response to L-stepholidine, a dopamine D1 receptor agonist and D2 receptor antagonist. We found significant sex differences in basal levels of phosphorylated protein kinase A (p-PKA) and glycogen synthase kinase (GSK)-3β in wild type mice that were absent in Fmr1-KO mice. In wild-type mice, L-stepholidine increased p-PKA in males but not female mice, decreased p-GSK-3 in female mice and increased p-GSK-3 in male mice. Conversely, in Fmr1-KO mice, L-stepholidine increased p-PKA and p-GSK-3β in females, and decreased p-PKA and p-GSK-3β in males.


2021 ◽  
Vol 25 (6) ◽  
pp. 669-676
Author(s):  
E. I. Denisova ◽  
M. M. Savinkova ◽  
E. N. Makarova

The consumption of food rich in sugar and fat provokes obesity. Prenatal conditions have an impact on taste preferences and metabolism in the adult offspring, and this impact may manifest differently in different sexes. An increase in blood leptin level in pregnant females reduces the risk of obesity and insulin resistance in the offspring, although the mechanisms mediating this effect are unknown. Neither is it known whether maternal leptin affects taste preferences. In this study, we investigated the effect of leptin administration to pregnant mice on the development of diet-induced obesity, food choice, and gene expression in the liver and muscles of the offspring with regard to sex. Leptin was administered to female mice on days 11, 12, and 13 of pregnancy. In male and female offspring, growth rate and intake of standard chow after weaning, obesity development, gene expression in the liver and muscles, and food choice when kept on a high-calorie diet (standard chow, lard, sweet cookies) were recorded. Leptin administration to pregnant females reduced body weight in the female offspring fed on the standard diet. When the offspring were given a high-calorie diet, leptin administration inhibited obesity development and reduced the consumption of cookies only in males. It also increased the consumption of standard chow and the mRNA levels of genes for the insulin receptor and glucose transporter type 4 in the muscles of both male and female offspring. The results demonstrate that an increase in blood leptin levels in pregnant females has a sex-specific effect on the metabolism of the offspring increasing resistance to obesity only in male offspring. The mechanism underlying this effect includes a shift in food preference in favor of a balanced diet and maintenance of insulin sensitivity in muscle tissues.


2021 ◽  
Vol 20 (3) ◽  
pp. 46-53
Author(s):  
O. I. Kit ◽  
E. M. Frantsiyants ◽  
I. V. Neskubina ◽  
N. D. Cheryarina ◽  
A. I. Shikhlyarova ◽  
...  

Aim. To study the Bcl-2 level in mitochondria of various organs in female mice with standard and stimulated growth of an experimental B16/F10 melanoma.Materials and methods. The study included С57ВL/6 female mice (n = 168). The experimental animals were divided into the following groups: an intact group (n = 21), a group with modelled chronic neuropathic pain (CNP) (n = 21), an M group with B16/F10 melanoma (n = 63), and a CNP + M group (n = 63). The Bcl-2 concentration (ng / mg protein) in mitochondrial samples was determined by ELISA (Thermo Fisher Scientific, Austria). Statistical analysis of the results was carried out using Statistica 10.0.Results. Compared to the Bcl-2 levels in the intact animals, CNP decreased this parameter in the cardiac mitochondria by 1.3 times, while increasing it by 5.9 times in the skin mitochondria. In the dynamics of standard melanoma growth, the Bcl-2 content changed compared with the corresponding intact values in the mitochondria of the brain, heart, and skin, but did not change in the liver and kidneys. In the mitochondria in melanoma, the Bcl-2 levels were high throughout the entire period of standard tumor growth in comparison with the intact skin. The stimulated melanoma growth in CNP was involving more organs into the pathological process as the tumor was growing. Thus, in comparison with the values in the CNP group, the mitochondrial Bcl-2 levels changed in the heart at week 1; in the heart and skin – at week 2; in the heart, skin, and brain – at week 3. The Bcl-2 levels did not change in the liver and kidney mitochondria. In the mitochondria in the CNP-stimulated melanoma, the Bcl-2 levels were lower than in the skin mitochondria in CNP throughout the entire tumor growth period.Conclusion. The liver and kidney mitochondria are somewhat Bcl-2 stable in both standard and stimulated tumor growth. It is assumed that different Bcl-2 dynamics in the mitochondria in melanoma depending on the variant of tumor development reflects the modulating effect of CNP and the ability to change the Bcl-2 levels according to the growth phase.


2021 ◽  
Vol 30 (4) ◽  
pp. 467-477
Author(s):  
B Obermueller ◽  
C Castellani ◽  
H Till ◽  
B Reininger-Gutmann ◽  
G Singer

The aim of our study was to assess the nest-building behaviour of two mouse (Mus musculus) strains using different nesting materials and examine possible sex- and housing-specific effects. Adult mice of two strains (C57BL/6J; n = 64 and BALB/cAnNCrl; n = 99) were randomly allocated to the following housing groups: single-housed male, single-housed female, pair-housed male and pair-housed female. One of the following nest-building materials was placed in each home-cage in a random order: nestlets (Plexx BV, The Netherlands), cocoons (Carfil, Belgium), wooden wool, crinklets and compact (all three, Safe, Germany). The following day, nests were rated applying a nest-scoring scale ranging from 0 to 10, the nests were removed, and a different nest-building material provided. In both tested strains, nestlets achieved the highest nest-building scores when compared to the other four nest-building materials. All nest-building materials scored higher in BALB/c mice compared to C57BL/6J animals reaching statistical significance in crinklets only. Sex comparison revealed that female C57BL/6J mice only scored significantly higher using crinklets than males and BALB/c female mice were rated significantly higher using wooden wool, cocoons and compact than their male counterparts. While pair-housed C57BL/6J animals built higher-rated nests than single-housed mice in the C57BL/6J strain in all five materials tested, the scores were not significantly different in the BALB/c strain. Results of the present study reveal significant strain-, sex- and housing-related influences on the complexity of nests using different standardised building materials. Such observations need to be taken into account when planning the optimal enrichment programme for laboratory animals.


2021 ◽  
pp. 1-42
Author(s):  
Aatish Mahajan ◽  
Divika Sapehia ◽  
Beenish Rahat ◽  
Jyotdeep Kaur

Abstract Maternal folic acid and vitamin B12 (B12) status during pregnancy influence fetal growth. This study elucidated the effect of altered dietary ratio of folic acid and B12 on the regulation of H19/IGF2 locus in C57BL/6 mice. Female mice were fed diets with 9 combinations of folic acid and B12 for 4 weeks. They were mated and the offspring born (F1) were continued on the same diet for 6 weeks post-weaning and were allowed to mate. The placenta and fetal (F2) tissues were collected at day 20 of gestation. H19 overexpression observed under dietary deficiency of folate combined with normal B12 (BNFD) was associated with an increased expression of miR-675 in maternal and fetal tissues. Insulin-like growth factor 2 (IGF2), expression was decreased under folic acid deficient conditions combined with normal, deficient or over-supplemented state of B12 (BNFD, BDFD, BOFD) in fetal tissues along with B12 deficiency combined with normal folic acid (BDFN) in the placenta. The altered expression of imprinted genes under folic acid deficient conditions was related to decreased serum levels of folate and body weight (F1). Hypermethylation observed at the H19 differentially methylated region (DMR) (in BNFD) might be responsible for the decreased expression of IGF2 in female fetal tissues. IGF2 DMR2 was found to be hypomethylated and associated with low serum B12 levels with B12 deficiency in fetal tissues. Results suggest that the altered dietary ratio of folic acid and B12 affects the in-utero development of the fetus in association with altered epigenetic regulation of H19/IGF2 locus.


Author(s):  
Jazmin A Cole ◽  
Mackenzie N Kehmeier ◽  
Bradley R Bedell ◽  
Sahana Krishna Kumaran ◽  
Grant D Henson ◽  
...  

Abstract Vascular endothelial function declines with age on average, but there is high variability in the magnitude of this decline within populations. Measurements of frailty, known as frailty index (FI), can be used as surrogates for biological age, but it is unknown if frailty relates to the age-related decline in vascular function. To examine this relation, we studied young (4-9 months) and old (23-32 months) C57BL6 mice of both sexes. We found that FI was greater in old compared with young mice, but did not differ between old male and female mice. Middle cerebral artery (MCA) and mesenteric artery endothelium-dependent dilation (EDD) also did not differ between old male and female mice; however, there were sex differences in the relations between FI and EDD. For the MCA, FI was inversely related to EDD among old female mice, but not old male mice. In contrast, for the mesenteric artery, FI was inversely related to EDD among old male mice, but not old female mice. A higher FI was related to a greater improvement in EDD with the superoxide scavenger TEMPOL in the MCAs for old female mice and in the mesenteric arteries for old male mice. FI related to mesenteric artery gene expression negatively for extracellular superoxide dismutase (Sod3) and positively for interleukin-1β (Il1b). In summary, we found that the relation between frailty and endothelial function is dependent on sex and the artery examined. Arterial oxidative stress and pro-inflammatory signaling are potential mediators of the relations of frailty and endothelial function.


2021 ◽  
Vol 19 (1) ◽  
pp. 73-83
Author(s):  
M. S. Jahan ◽  
M. S. Islam ◽  
M. Gautam ◽  
M. E. R. Bhuiyan

Background: The experiment was conducted to evaluate the effect of different dosages of lead in the hematological parameters of mice and to observe the antitoxic role of Vitamin E and Selenium in induced lead toxicities. Moreover, the toxic effect of lead in the reproduction of female mice was also examined. Methods: A total of 72 (48 male and 24 female) Swiss albino mice were used in the experiment. After adaptation, 42 male mice were selected for hematological studies and divided into seven groups (n=6) where Group A represented healthy control mice and Group B, C, and D were treated with lead acetate at the rate of 0.5mg/kg, 1mg/kg and 2mg/kg respectively. Similarly, three other groups B+, C+, and D+ were treated with lead acetate plus Vitamin E and Selenium at the rate of 2ml per liter drinking water. A total of 24 female mice were divided into four groups (n=6), group E represented control mice and Group F, G, and H were treated with lead acetate at the rate of 0.5mg/kg, 1mg/kg, and 2mg/kg for three weeks followed by matting and treatment was continued for another one week of gestation. Blood sample was analyzed from the hematological study group. Result: The lead treatment caused a dose-dependent decrease in the value of Hb and PCV significantly whereas the value of TEC and TLC were significantly decreased in Group C and D in relation to Control. The value of ESR increased significantly in a dose-dependent manner in Group D in relation to Control whereas MCV and MCH values were significantly decreased than that of control. The value of TEC, Hb, PCV, ESR, and TLC improved in the Lead plus Vitamin E- Selenium treated group as compared to the Lead treated group but, only Group C+ showed significant improvement as compared to Group C. The value of neutrophil and monocyte were significantly decreased were as lymphocyte and eosinophil were significantly increased relative to control. There was a dose-dependent effect of lead in pregnancy of female mice with the highest effect (premature delivery and infant mortality) on high dose treated mice. Conclusion: It can be concluded that lead has a great impact on hematological parameters and has an effect on various systems of the body. Premature birth and abortion are major effects of lead toxicity. Our results suggest that hemolysis of RBC and or impairment of erythropoiesis may be caused by lead toxicity and the hematological values can be restored by the use of Vitamin E plus Selenium.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2801
Author(s):  
Ramkumar Mohan ◽  
Seokwon Jo ◽  
Elina Da Sol Chung ◽  
Eunice Oribamise ◽  
Amber Lockridge ◽  
...  

The nutrient-sensor O-GlcNAc transferase (Ogt), the sole enzyme that adds an O-GlcNAc-modification onto proteins, plays a critical role for pancreatic β-cell survival and insulin secretion. We hypothesized that β-cell Ogt overexpression would confer protection from β-cell failure in response to metabolic stressors, such as high-fat diet (HFD) and streptozocin (STZ). Here, we generated a β-cell-specific Ogt in overexpressing (βOgtOE) mice, where a significant increase in Ogt protein level and O-GlcNAc-modification of proteins were observed in islets under a normal chow diet. We uncovered that βOgtOE mice show normal peripheral insulin sensitivity and glucose tolerance with a regular chow diet. However, when challenged with an HFD, only female βOgtOE (homozygous) Hz mice developed a mild glucose intolerance, despite increased insulin secretion and normal β-cell mass. While female mice are normally resistant to low-dose STZ treatments, the βOgtOE Hz mice developed hyperglycemia and glucose intolerance post-STZ treatment. Transcriptome analysis between islets with loss or gain of Ogt by RNA sequencing shows common altered pathways involving pro-survival Erk and Akt and inflammatory regulators IL1β and NFkβ. Together, these data show a possible gene dosage effect of Ogt and the importance O-GlcNAc cycling in β-cell survival and function to regulate glucose homeostasis.


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