scholarly journals Sex Differences in Animal Models of Sodium-Valproate-Induced Autism in Postnatal BALB/c Mice: Whole-Brain Histoarchitecture and 5-HT2A Receptor Biomarker Evidence

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 79
Author(s):  
Balaji Gouda ◽  
Sukesh Narayan Sinha ◽  
Meram Chalamaiah ◽  
Validandi Vakdevi ◽  
Patangay Shashikala ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Purkinje Cells ◽  
Morphological Changes ◽  
Autism Spectrum ◽  
Nervous System Development ◽  
Receptor Protein ◽  
Morphological Observation ◽  
Male And Female ◽  
Treated Male ◽  
Female Mice

Autism spectrum disorder (ASD) is characterised by problems with social interaction, verbal and nonverbal communication and repetitive behaviour. In mice, the 14th postnatal day is believed to correspond to the third trimester of human embryonic development and is considered a vital period for central nervous system development. It has been shown that ASD affects 2 to 3 times more male than female individuals. In the present study, ASD was induced in 14 postnatal day (PND) BALB/c mice using valproic acid (VPA). VPA administration brought about substantial differences in the histoarchitecture of the brain in both male and female mice, linked to behavioural deficits. We observed that both male and female mice showed similar morphological changes in the prefrontal cortex, hippocampus and Purkinje cells. We also observed hair loss from PND 17 to 25, which was again similar between male and female mice. However, there were higher rates of change in the cerebral cortex, frontal cortex and temporal lobe and hippocampus in VPA-treated male animals. With respect to the cerebellum, we did not observe any alterations by haematoxylin and eosin (H&E) staining, but detailed morphological observation using scanning electron microscopy (SEM) showed a higher rate of phenotype changes in VPA-treated male animals. Moreover, 5-HT2A receptor protein levels were upregulated in the cerebral cortex, hippocampus and Purkinje cells in VPA-treated male mice compared with control animals and VPA-treated female mice, as shown by immunohistochemical analysis. Based on all these findings, we conclude that male animals are more susceptible to VPA-induced ASD than females.

scholarly journals Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice

2020 ◽  
Author(s):  
Nicole Martin-Kenny ◽  
Nathalie G. Bérubé
Keyword(s):  
Repeated Measures ◽  
Susceptibility Gene ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Autism Spectrum ◽  
Conditional Knockout ◽  
Male And Female ◽  
Female Mice ◽  
Excitatory Neurons ◽  
Behavioural Tests

AbstractBackgroundAlpha-thalassemia/mental retardation, X-linked, or ATRX, is an autism susceptibility gene that encodes a chromatin remodeler. Mutations of ATRX result in the ATR-X intellectual disability syndrome and have been identified in autism spectrum disorder (ASD) patients. The mechanisms by which ATRX mutations lead to autism and autistic-like behaviours are not yet known. To address this question, we generated mice with postnatal Atrx inactivation in excitatory neurons of the forebrain and performed a battery of behavioural assays that assess autistic-like behaviours.MethodsMale and female mice with a postnatal conditional knockout of Atrx were tested in a battery of behavioural tests that assess autistic features. We utilized paradigms that measure social behaviour, repetitive and stereotyped behaviours, as well as sensory gating. Statistics were calculated by two-way repeated measures ANOVA with Sidak’s multiple comparison test or unpaired Student’s T-tests as indicated.ResultsThe behaviour tests revealed no significant differences between Atrx-cKO and control mice. We identified sexually dimorphic changes in odor habituation and discrimination; however, these changes did not correlate with social deficits. We additionally observed sex-specific differences in sociability, vertical episodes, and acoustic startle response when results were analyzed by sex.ConclusionThe postnatal knockout of Atrx in forebrain excitatory neurons does not lead to autism-related behaviours in male or female mice.

Suppression of expulsion ofAspiculuris tetrapterain hydrocortisone and methotrexate treated mice

Parasitology ◽  
1975 ◽  
Vol 71 (1) ◽  
pp. 109-116 ◽  
Author(s):  
Jerzy M. Behnke
Keyword(s):  
Primary Infection ◽  
Larval Growth ◽  
Male And Female ◽  
Treated Male ◽  
Female Mice ◽  
The Third ◽  
Delayed Rejection ◽  
Aspiculuris Tetraptera ◽  
Anterior Migration

Hydrocortisone treated male and female mice, given a primary infection withAspiculuris tetraptera, did not reject the worms during the third week of infection. Mice given hydrocortisone during the first week of infection had elevated worm burdens on day 10, suggesting that some worm loss was encountered during the anterior migration in control mice. Furthermore, this temporary period of treatment was sufficient totally to suppress rejection and to allow the parasite to persist until day 28. Methotrexate also significantly delayed rejection, but larval growth was retarded in treated mice. These results, it is suggested, add strength to the hypothesis that the loss ofA. tetrapterain a primary infection in mice, is an immunological phenomenon.

scholarly journals Brain-synthesized estrogens regulate cortical migration in a sexually divergent manner

2019 ◽  
Author(s):  
Katherine J. Sellers ◽  
Matthew C.S. Denley ◽  
Atsushi Saito ◽  
Atsushi Kamiya ◽  
Deepak P. Srivastava
Keyword(s):  
Cerebral Cortex ◽  
Opposite Effect ◽  
Ventricular Zone ◽  
Cortical Plate ◽  
Local Synthesis ◽  
Male And Female ◽  
Sexual Dimorphisms ◽  
Female Mice ◽  
Males And Females

AbstractEstrogens play an important role in the sexual dimorphisms that occur during brain development, including the neural circuitry that underlies sex-typical and socio-aggressive behaviors. Aromatase, the enzyme responsible for the conversion of androgens to estrogens, is expressed at high levels during early development in both male and female cortices, suggesting a role for brain-synthesized estrogens during corticogenesis. This study investigated how the local synthesis of estrogens affects neurodevelopment of the cerebral cortex, and how this differs in males and females by knockdown expression of the Cyp19a1 gene, which encodes aromatase, between embryonic day 14.5 and postnatal day 0 (P0). The effects of Cyp19a1 knockdown on neural migration was then assessed. Aromatase was expressed in the developing cortex of both sexes, but at significantly higher levels in male than female mice. Under basal conditions, no obvious differences in cortical migration between male and female mice were observed. However, knockdown of Cyp19a1 increased the number GFP-positive cells in the cortical plate, with a concurrent decrease in the subventricular zone/ventricular zone in P0 male mice. The opposite effect was observed in females, with a significantly reduced number of GFP-positive cells migrating to the cortical plate. These findings have important implications for our understanding of the role of fetal steroids for neuronal migration during cerebral cortex development. Moreover, these data indicate that brain-synthesized estrogens regulate radial migration through distinct mechanisms in males and females.

Concomitant development of oral dyskinesia and memory deficits in reserpine-treated male and female mice

2002 ◽  
Vol 132 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Regina H Silva ◽  
Vanessa C Abı́lio ◽  
Danila Torres-Leite ◽  
Marcelo Bergamo ◽  
Cibele C Chinen ◽  
...  
Keyword(s):  
Memory Deficits ◽  
Male And Female ◽  
Treated Male ◽  
Female Mice ◽  
Oral Dyskinesia

Induction of murine α-foetoprotein synthesis by oestradiol

1984 ◽  
Vol 106 (1) ◽  
pp. 141-144 ◽  
Author(s):  
J. Hau ◽  
J. Chemnitz ◽  
B. Teisner ◽  
D. Tornehave ◽  
P. Svendsen
Keyword(s):  
Liver Tissue ◽  
Late Pregnancy ◽  
Serum Levels ◽  
Immunohistochemical Examination ◽  
Male And Female ◽  
Treated Male ◽  
Female Mice ◽  
Adult Mice

Abstract. The synthesis of murine α-foetoprotein (m-AFP) was induced in 43 out of 47 adult mice of both sexes by sc administration of 100 μg oestradiol-17β every second day. The m-AFP serum levels of the oestrogen treated male and female mice were 7 and 17%, respectively, of the levels in mice during late pregnancy. Immunohistochemical examination of liver tissue revealed the intracellular presence of m-AFP in less than 0.5% of the hepatocytes scattered throughout the liver of the oestrogen treated mice.

12 Sex-related differential susceptibility to ponatinib-induced cardiotoxicity and its relationship to modulation of notch signalling in a muine model

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Rosalinda Madonna ◽  
Damiana Pieragostino ◽  
Maria Concetta Cufaro ◽  
Piero Del Boccio ◽  
Angela Pucci ◽  
...  
Keyword(s):  
Cell Death ◽  
Cardiac Fibrosis ◽  
Kinase Inhibitor ◽  
Left Ventricular Systolic Dysfunction ◽  
Differential Susceptibility ◽  
Left Ventricular ◽  
Male Mice ◽  
Male And Female ◽  
Treated Male ◽  
Female Mice

Abstract Aims Ponatinib (PON), a tyrosine kinase inhibitor approved in chronic myeloid leukaemia, has proven cardiovascular toxicity. Although sex is a risk factor for PON-induced cardiotoxicity in humans, little is known about its mechanisms, in general, and sex-related mechanisms in particular. To determine the mechanisms of sex-related PON-induced cardiotoxicity and identify potential rescue strategies in a murine model. Methods Twenty-four-month-old male and female C57B5 mice were treated with 3 mg/kg/day of PON or vehicle via oral gavage for 28 days, with/without siRNA-Notch1 or siRNA-scrambled via tail vein every 3 days. Results PON + scrambled siRNA-treated male mice had a higher number of TUNEL-positive cells, a higher percentage of senescence-associated β-galactosidase positive senescent cardiac areas, as well as a lower reactivity degree for the survival marker Bmi1 than female counterparts. Proteomics analysis of cardiac tissue showed upstream activation of nitric oxide synthase (NOS) type 2, downstream activation of cell death and production of reactive oxygen species in PON + scrambled siRNA- compared to vehicle or PON + Notch1 siRNA-treated male mice. Upstream analysis showed beta-estradiol activation, while downstream analysis showed activation of cell survival and inhibition of cell death in PON + scrambled siRNA compared to vehicle-treated female mice. PON + scrambled siRNA-treated mice also showed a down-regulation of cardiac actin, which was more marked in male; as well as vessel density, which was more marked in female mice. Female hearts showed a greater extent of cardiac fibrosis than male counterparts at baseline, with no significant changes after PON treatment. In contrast, PON + scrambled siRNA-treated mice had less fibrosis than vehicle or PON + Notch1-siRNA-treated mice. Left ventricular systolic dysfunction shown in PON + scrambled siRNA-treated male mice and—to a lesser extent—by female mice was similarly reversed in both PON + Notch1-siRNA-treated male and female mice (Table 1). Conclusions We found a sex-related differential susceptibility and Notch1 modulation in PON-induced cardiotoxicity. This can improve our understanding of sex-related differences and help identify biomarkers in PON cardiotoxicity.

scholarly journals Mutant Cx30-A88V mice exhibit hydrocephaly and sex-dependent behavioral abnormalities, implicating a functional role for Cx30 in the brain

2021 ◽  
Vol 14 (1) ◽  
pp. dmm046235
Author(s):  
Nicole M. Novielli-Kuntz ◽  
Eric R. Press ◽  
Kevin Barr ◽  
Marco A. M. Prado ◽  
Dale W. Laird
Keyword(s):  
Connexin 43 ◽  
Cell Layer ◽  
Ependymal Cell ◽  
Morphological Changes ◽  
Abnormal Behavior ◽  
Brain Morphology ◽  
Ependymal Cells ◽  
Male And Female ◽  
Female Mice ◽  
The Brain

ABSTRACTConnexin 30 (Cx30; also known as Gjb6 when referring to the mouse gene) is expressed in ependymal cells of the brain ventricles, in leptomeningeal cells and in astrocytes rich in connexin 43 (Cx43), leading us to question whether patients harboring GJB6 mutations exhibit any brain anomalies. Here, we used mice harboring the human disease-associated A88V Cx30 mutation to address this gap in knowledge. Brain Cx30 levels were lower in male and female Cx30A88V/A88V mice compared with Cx30A88V/+ and Cx30+/+ mice, whereas Cx43 levels were lower only in female Cx30 mutant mice. Characterization of brain morphology revealed a disrupted ependymal cell layer, significant hydrocephalus and enlarged ventricles in 3- to 6-month-old adult male and female Cx30A88V/A88V mice compared with Cx30A88V/+ or Cx30+/+ sex-matched littermate mice. To determine the functional significance of these molecular and morphological changes, we investigated a number of behavioral activities in these mice. Interestingly, only female Cx30A88V/A88V mice exhibited abnormal behavior compared with all other groups. Cx30A88V/A88V female mice demonstrated increased locomotor and exploratory activity in both the open field and the elevated plus maze. They also exhibited dramatically reduced ability to learn the location of the escape platform during Morris water maze training, although they were able to swim as well as other genotypes. Our findings suggest that the homozygous A88V mutation in Cx30 causes major morphological changes in the brain of aging mice, possibly attributable to an abnormal ependymal cell layer. Remarkably, these changes had a more pronounced consequence for cognitive function in female mice, which is likely to be linked to the dysregulation of both Cx30 and Cx43 levels in the brain.

scholarly journals Sex-related differential susceptibility to ponatinib-induced cardiotoxicity and its relationship to modulation of Notch signaling in a murine model

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
R Madonna ◽  
D Pieragostino ◽  
M C Cufaro ◽  
P Del Boccio ◽  
A Pucci ◽  
...  
Keyword(s):  
Cell Death ◽  
Murine Model ◽  
Kinase Inhibitor ◽  
Left Ventricular Systolic Dysfunction ◽  
Differential Susceptibility ◽  
Left Ventricular ◽  
Male Mice ◽  
Male And Female ◽  
Treated Male ◽  
Female Mice

Abstract Background Ponatinib (PON), a tyrosine kinase inhibitor approved in chronic myeloid leukemia, has proven cardiovascular toxicity. Although sex is a risk factor for PON-induced cardiotoxicity in humans, little is known about its mechanisms in general, and sex-related mechanisms in particular. Objectives To determine the mechanisms of sex-related PON-induced cardiotoxicity and identify potential rescue strategies in a murine model. Methods 24-months-old male and female C57B5 mice were treated with 3 mg/kg/day of PON or vehicle via oral gavage for 28 days, with/without siRNA-Notch1 or siRNA-scrambled via tail vein every 3 days. Results PON + scrambled siRNA-treated male mice had a higher number of TUNEL-positive cells, a higher percentage of senescence-associated β-galactosidase positive senescent cardiac areas, as well as a lower reactivity degree for the survival marker Bmi1 than female counterparts. Proteomics analysis of cardiac tissue showed upstream activation of nitric oxide synthase (NOS) type 2, downstream activation of cell death and production of reactive oxygen species in PON + scrambled siRNA- compared to vehicle or PON + Notch1 siRNA-treated male mice. Upstream analysis showed beta-estradiol activation, while downstream analysis showed activation of cell survival and inhibition of cell death in PON + scrambled siRNA compared to vehicle-treated female mice. PON + scrambled siRNA-treated mice also showed a downregulation of cardiac actin, which was more marked in male; as well as vessel density, which was more marked in female mice. Female hearts showed a greater extent of cardiac fibrosis than male counterparts at baseline, with no significant changes after PON treatment. In contrast, PON + scrambled siRNA-treated mice had less fibrosis than vehicle or PON + Notch1-siRNA-treated mice. Left ventricular systolic dysfunction shown in PON + scrambled siRNA-treated male mice and - to a lesser extent - by female mice was similarly reversed in both PON + Notch1-siRNA-treated male and female mice (Table 1). Conclusions We found a sex-related differential susceptibility and Notch1 modulation in PON-induced cardiotoxicity. This can improve our understanding of sex-related differences and help identify biomarkers in PON cardiotoxicity. FUNDunding Acknowledgement Type of funding sources: None.

A subchronic oral toxicity study on medical herb extract, KIOM CRC#BP10A, in male and female mice

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
ES Cho ◽  
YJ Lee ◽  
JS Park ◽  
J Kim ◽  
NS Kim ◽  
...  
Keyword(s):  
Toxicity Study ◽  
Oral Toxicity ◽  
Male And Female ◽  
Female Mice ◽  
Subchronic Oral Toxicity Study ◽  
Herb Extract

THE PITUITARY AND ADRENAL RESPONSES TO ADMINISTRATION OF OESTRIOL IN GONADECTOMIZED RATS

1961 ◽  
Vol 38 (1) ◽  
pp. 50-58 ◽  
Author(s):  
N. E. Borglin ◽  
L. Bjersing
Keyword(s):  
Pituitary Gland ◽  
Adrenal Cortex ◽  
Clinical Experience ◽  
Uterine Cervix ◽  
Morphological Changes ◽  
Physiological Significance ◽  
Female Rats ◽  
Experimental Conditions ◽  
Male And Female ◽  
Male And Female Rats

ABSTRACT Oestriol (oestra-1,3,5(10)-triene-3,16α,17β-triol) is a weakly oestrogenic substance which, however, in contrast to what was formerly believed, is of physiological significance. Its effect is localized largely to the uterine cervix and vagina. Clinical experience argues both for and against an effect on the pituitary gland. This investigation is concerned with the morphological changes in the pituitary gland and adrenal cortex of gonadectomized male and female rats after the injection of oestriol. It was found that oestriol has the same type of action on these glands as other oestrogens, but under the experimental conditions used, this effect proved much weaker than that produced by oestradiol (oestra-1,3,5(10)-triene-3,17β-diol).

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