Mature Male Mice Research Articles

Inhibition of ROS1 activity with lorlatinib reversibly suppresses fertility in male mice.

Inhibition of sperm maturation in the epididymis is a promising post-testicular strategy for short-acting male contraceptives. It has been shown that ROS1, a receptor tyrosine kinase expressed in the epididymis, is essential for epididymal differentiation, sperm maturation, and male fertility in mice. However, it is unknown if inhibition of ROS1 suppresses male fertility reversibly. Our study aimed to investigate the effects of ROS1 inhibitor administration in male mice on sperm function and fertility. We used lorlatinib, an anti-cancer drug that inhibits ROS1. We treated 10-week-old sexually mature male mice with lorlatinib for 3weeks and performed fertility tests, histological staining, in vitro fertilization, sperm motility analyses, and immunoblot analyses. We also performed the same analyses 3weeks after discontinuing the lorlatinib treatment. Inhibition of ROS1 for 3weeks suppressed male fertility. Lorlatinib-treated mice showed no overt abnormalities in testicular sections, but epithelium maintenance of the epididymal initial segment was impaired. Accordingly, the levels of OVCH2, RNASE10, and ADAM28, which are expressed in the epididymis, decreased. Spermatozoa from the lorlatinib-treated mice lost their ability to bind to the zona pellucida, and ADAM3 processing was abnormal. Sperm motility was also impaired in the lorlatinib-treated mice. These impairments were recovered 3weeks after discontinuing the drug treatment. Inhibition of ROS1 with lorlatinib suppressed sperm maturation and male fertility reversibly. Future exploration of molecules that specifically target ROS1 and the ROS1 pathway in the epididymis may lead to the development of safe and reversible male contraceptives.

Reducing the Сardiotoxicity of Daunorubicin by Conjugation with Natural Sesquiterpene Lactones

We present the results of a histological study into the cardiotoxicity of conjugates of daunorubicin with dehydrocostus lactone and epoxyisoalantolactone in mature male mice of the C57BL/6 line. The effect of conjugates on the morphology of cardiomyocytes and the structure of the left ventricular myocardium in mice was studied.

The effects of apelin-13 in a mouse model of post-traumatic stress disorder.

The objective is to investigate the effects of apelin-13 in models of post-traumatic stress disorder (PTSD). Mature male CD1 mice were subjected to the single prolonged stress method to induce PTSD-related behaviors. These behaviors were then evaluated using the elevated plus maze test, Morris water maze test, and open field test. Hippocampal neural cell death was assessed using propidium iodide labeling. The expression of hippocampal autophagy pathway-associated proteins was determined through immunoblotting analysis, and LC3 levels were also measured via quantitative real-time reverse transcription-PCR. The results demonstrate that administration of apelin-13 suppressed PTSD-induced hippocampal neural cell death and alleviated PTSD-related behaviors in mice. Additionally, PTSD led to an up-regulation of LC3 and FoxO3a, and down-regulation of P62, p-PI3K, p-Akt, and p-FoxO3a in the hippocampus. However, these changes were reversed by apelin-13 treatment. These findings support the hypothesis that apelin-13 prevents the development of PTSD-like behavior and inhibits autophagy of neuronal cells in a mouse model of PTSD. Apelin-13 may hold potential as a therapeutic agent for PTSD in clinical applications.

HDAC5 controls a hypothalamic STAT5b-TH axis, the sympathetic activation of ATP-consuming futile cycles and adult-onset obesity in male mice

With age, metabolic perturbations accumulate to elevate our obesity burden. While age-onset obesity is mostly driven by a sedentary lifestyle and high calorie intake, genetic and epigenetic factors also play a role. Among these, members of the large histone deacetylase (HDAC) family are of particular importance as key metabolic determinants for healthy ageing, or metabolic dysfunction. Here, we aimed to interrogate the role of class 2 family member HDAC5 in controlling systemic metabolism and age-related obesity under non-obesogenic conditions. Starting at 6 months of age, we observed adult-onset obesity in chow-fed male global HDAC5-KO mice, that was accompanied by marked reductions in adrenergic-stimulated ATP-consuming futile cycles, including BAT activity and UCP1 levels, WAT-lipolysis, skeletal muscle, WAT and liver futile creatine and calcium cycles, and ultimately energy expenditure. Female mice did not differ between genotypes. The lower peripheral sympathetic nervous system (SNS) activity in mature male KO mice was linked to higher dopaminergic neuronal activity within the dorsomedial arcuate nucleus (dmARC) and elevated hypothalamic dopamine levels. Mechanistically, we reveal that hypothalamic HDAC5 acts as co-repressor of STAT5b over the control of Tyrosine hydroxylase (TH) gene transactivation, which ultimately orchestrates the activity of dmARH dopaminergic neurons and energy metabolism in male mice under non-obesogenic conditions.

Effect of moringa seed extract in chlorpyrifos-induced cerebral and ocular toxicity in mice.

Chlorpyrifos (CPF) is one of the most commonly used organophosphosphate-based (OP) insecticides. Its wide use has led to higher morbidity and mortality, especially in developing countries. Moringa seed extracts (MSE) have shown neuroprotective activity, antioxidant, anti-inflammatory, and antibacterial features. The literature lacks data investigating the role of MSE against CPF-induced cerebral and ocular toxicity in mice. Therefore, we aim to investigate this concern. A total of 40 mature male Wistar Albino mice were randomly distributed to five groups. Initially, they underwent a one-week adaptation period, followed by a one-week treatment regimen. The groups included a control group that received saline, MSE 100 mg/kg, CPF 12 mg/kg, CPF-MSE 50 mg/kg, and CPF-MSE 100 mg/kg. After the treatment phase, analyses were conducted on serum, ocular, and cerebral tissues. MSE100 and CPF-MSE100 normalized the pro-inflammatory markers (interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)) and AChE serum levels. CPF-MSE50 significantly enhanced these serum levels compared to CPF; however, it showed higher levels compared to the control. Moreover, the tissue analysis showed a significant decrease in oxidative stress (malondialdehyde (MDA) and nitric oxide (NO)) and an increase in antioxidant markers (glutathione (GSH), glutathione peroxidase (GSH-PX)), superoxide dismutase (SOD), and catalase (CAT) in the treated groups compared to CPF. Importantly, the significance of these effects was found to be dose-dependent, particularly evident in the CPF-MSE100 group. We conclude that MSE has a promising therapeutic effect in the cerebral and ocular tissues of CPF-intoxicated mice, providing a potential solution for OP public health issues.

Impact of Benzo (a) Pyrene on Thyroid Glands and their Associated Hormones of Male Mice Mus musculus

Benzo [a] pyrene is the main representative of polycyclic aromatic hydrocarbons, and has been repeatedly found in the air, surface water, soil, and sediments. Human exposure to Benzo [a] pyrene is therefore common. Benzo (a) pyrane (BaP) which is mainly presented in newspaper ink and inhibits the function of the thyroid and other endocrine glands of the human system, due to several disorders that occur in the human body. Healthy mature male mice Mus musculus having weight of 125 ± 5 gm were used for the experiments. The effects of a Benzo (a) pyrene (0.65mg/25g body weight/twice in a week) during experimental periods of 60 and 90 days in male mice Mus musculus showed significant difference in body weights compared to control. We assessed the hormonal estimation of thyroid treated with Benzo (a) pyrene by using an appropriate ELISA assay kit and histopathological changes were observed under a light microscope (magnifications 100X) in the thyroid tissue of male mice Mus musculus exposed to BaP after 60 and 90 days. During the study, we observed that in treated mice thyroid hormone concertation was affected the structure of the thyroid follicles was disturbed and epithelial cells were necrotic compared with the control mice which indicates that the BaP may lead to changes in the thyroid morphology as well as secreted hormone concentration in exposed treated male mice.

Nephroprotective properties of Achillea millefolium green-formulated Au NPs in streptozotocin-induced diabetic nephropathy in mice: Introducing a novel therapeutic drug for the treatment of nephropathy

We have reported biosynthesis of Au NPs by using Achillea millefolium aqueous extract under mild procedure. Various techniques like UV–Vis, TEM, FE-SEM, EDS-elemental mapping and ICP-OES were used to characterize present nanoparticles. In the in vivo condition, streptozotocin (STZ) with dose of 60 mg/kg was used intraperitoneally for inducing diabetes in 100 mature male mice. The negative control mice were treated with normal saline and other mice were treated with glibenclamide (0.5 mg/kg) and Au nanoparticles (10 and 40 μg/kg) by gavage for 20 days. Additionally, 20 diabetic mice were considered as positive control and received the normal saline. Gold nanoparticles reduced the raised concentrations of urea and blood glucose in biochemical assays and volumes and lengths of vessels, loop of Henle, collecting ducts, and distal and proximal tubules in stereological assays in comparison with the untreated group. According to the obtained findings, gold nanoparticles can ameliorate the raised levels of biochemical parameters and prevent kidney structure damage in STZ-induced diabetic mice.

Anti-oxidant and anti-apoptotic effects of royal jelly against polystyrene microplastic-induced testicular injury in mice.

In recent years, microplastics (MPs), which are novel environmental contaminants measuring 5 mm in diameter, have garnered considerable attention. However, information regarding substances that can mitigate the dangers of MPs for animals remains extremely limited. Ninety days were devoted to the exposure of mature male mice to royal jelly (RJ) and 2 µm virgin polystyrene microplastics (PS-MPs) in this study. Pre-implantation embryo development; the structure of testis tissue; the gonadosomatic index; sperm parameters; RNA damage in germinal cells; the anti-oxidant capacity of the entire testis; and the activity of anti-oxidant enzymes in serum and testicular tissue, including TAC, SOD dismutase, CAT, GSH, and MDA, histomorphometric indices of the testis (tubular differentiation index, spermatogenesis index, and repopulation index), steroidogenic foci, and the quantity of apoptosis were assessed in the testis, respectively, through the measurement of pro-apoptosis (p53, Bax, and Caspase-3) and anti-apoptosis (Bcl-2) factors, as well as Hsp70 mediator. The results indicate that concurrent administration of RJ can confer a protective effect on mice exposed to microplastics by maintaining the structure of mitochondria and enhancement of the anti-oxidant defense system. Furthermore, RJ co-treatment decreased apoptosis and oxidant/anti-oxidant status, enhanced pre-implantation embryo development, and improved sperm characteristics and RNA damage in germ cells. The data confirm that royal jelly could protect the testis structure against polystyrene microplastic-induced testicular injury through anti-oxidant and anti-apoptotic properties.

Protective Potential of Ashwagandha, Against Pyrifluquinazon Induced Hepato-And Nephrotoxicity in Albino Mice

Globally, due to rise in dependence on the agricultural sector for food supply, the use of insecticides i.e., “Chemicals used to kill insects”, has been increasing day by day. One of these is Pyrifluquinazon. The emerging concern is that after field spray, this insecticide has the tendency to be incorporated into surface water and become a part of the food chain and so becomes toxic for both aquatic and terrestrial organisms. Objective: To investigate the protective potential of Ashwagandha against damaging effect of Pyrifluquinazon (PQZ) on liver and kidney of mature and healthy male albino mice. Methods: Albino mice were divided into four groups, each group contained five mice. First group was control, supplied with water while, three were treated groups (Dose, Dose + Antidote and Antidote group respectively) to check protective potential of Ashwagandha against PQZ induced hepato and nephrotoxicity in mice. The dose group was supplied with PQZ while Dose + Antidote group with PQZ and Ashwagandha as an antidote while the Antidote group was supplied with Ashwagandha. This was accomplished for 20 days trial. Blood sampling and dissection was done at 20th day. Blood sample were taken using intra cardiac sampling method for biochemistry while liver and kidney were separated from each group for histopathological studies. Results: The liver function test and kidney function were normal and indicated restoration of their normal function. Histopathological findings also revealed regeneration in damaged areas of liver and kidney tissues. Conclusions: The Findings of this study clearly revealed the protective potential of Ashwagandha against PQZ induced hepato and nephrotoxicity.

Migration, proliferation and cell death of regenerating liver macrophages in an experimental model

Relevance . Macrophages are the leading regulatory cell-lineage taking part in reparative processes in mammals, and the liver is no exception. The ratio of monocyte migration, proliferation and death of macrophages during liver regeneration requires further studies. The aim was to quantify the intensity of monocyte migration, cell proliferation and apoptosis of resident liver macrophages after its 70 % resection in a mouse model. Materials and Methods. We performed 70 % liver resection in sexually mature male BalbC mice. Cells of liver monocyte-macrophage system were obtained by magnetic sorting by marker F4/80. The immunophenotype of the isolated cells was further studied by cytofluorimetry, the level of proliferation and cell death, the content of cyclins and P53 was determined by western blot. Results and Discussion . It was found that after partial hepatectomy there is a marked migration of monocytes/macrophages positive for Ly6C and CD11b markers to the liver, the migration process starts already in the first day after the operation. On the same terms there is a rise in proliferative activity of macrophages, established by Ki67 marker, the peak of proliferation - 3 days after partial hepatectomy. A significant increase in the number of dying macrophages was found early after liver resection. Conclusion . The obtained data indicate that liver regeneration in mammals on the model in mice is accompanied by proliferation migration and cell death of macrophages. Taking into account the immunophenotype of macrophages, we can conclude that Ly6C+ blood monocytes migrate to the liver, and resident macrophages participate in proliferation. The obtained data confirm the universality of the course of reparative processes in mammals.

Effect of Azadirachta indica Leaf Extract on Some Biochemical Parameters in Wistar Albino Mice Infected with Plasmodium berghei

The use of medicinal plants in combating many tropical diseases including malaria is gaining wide acceptance owing to their many bioactive compounds. Malaria, which is caused by a Plasmodium parasite, and transmitted by the bite of infected mosquitoes is endemic in developing countries especially in Africa where it pose serious health challenge to the populace. This study evaluates the effect of Azadirachta indica leaf extract on some biochemical parameters in Wistar Albino mice infected with Plasmodiumberghei. A total of ninety (90) mature male swiss albino mice (free from infection and weighing between 25-35g) were used for the study. The animals were grouped into six classes (A-F) of fifteen (15) mice per group, per cage. Groups A to C served as the control groups [normal (uninfected plus distilled water), standard (infected plus Lonart (4mg/kg) and negative (infected plus distilled water)] respectively while groups D, E and F served as the treatment groups and were orally administered 100 mg/kg, 200 mg/kg and 400 mg/kg doses of leaf extract of Azadirachta indica for five (5) days consecutively. Malaria parasites (Plasmodium berghei, Anka strain) were inoculated using standard methods. At the end of the experimental periods, the animals were sacrificed and blood collected through cardiac puncture for bioassay studies. Activities of ALT, AST, ALP were determined using standard assay kits and concentrations of bilirubin (total and direct) as well as urea, creatinine, sodium, potassium, chloride and bicarbonate levels were carried out using standard methods. Results showed a significant increase (p<0.05) in serum activities of ALT and AST in extract treated animals when compared with the untreated control while there was significant decrease (p>0.05) in the serum activities of ALP in extract treated animals when compared with the untreated control. Results further showed an increase in the bilirubin (total and direct) levels of the extract treated groups as compared with the untreated control. Similar trends were observed for the levels of urea, creatinine, sodium, potassium and chloride. It could therefore be concluded that administration of Azadirachta indica leaf extract, though potent in fighting against malarial infection, could pose a threat to the liver and other organs of the body if not properly monitored.

Safety of the Drug Prospekta: a Preclinical Study of Acute and Repeated Dose Toxicity.

General toxic effect of the drug Prospekta (modified affinity purified antibodies to the brain-specific S100 protein) was studied on mature male and female mice and rats: acute toxicity with double intragastric and intraperitoneal administration of the maximum permissible doses at a 2-h interval, repeated dose toxicity with intragastric administration of the maximum permissible and close to therapeutic doses for 6 months. No lethal and toxic effects on animals were observed, including no toxic effects on vital systems, i.e., CNS and cardiovascular system, as well systems with the functions that may be temporarily disrupted (excretory and digestive systems). All the differences between animals of the experimental and control groups varied within the physiological range. It can be concluded that the drug produces no general toxic effect on laboratory animals.

SIRT1 induction in the skeletal muscle of male mice partially attenuates changes to whole-body metabolism in response to androgen deprivation

In males, androgens regulate whole body metabolism. The components in androgen target organs contributing to whole-body metabolic function remain ill defined. Sirtuin1 (SIRT1) protein levels are lower in the limb muscle of male mice subjected to androgen deprivation. Because SIRT1 can influence whole-body metabolism, the purpose was to assess whether muscle specific SIRT1 induction attenuated changes to whole-body metabolism in response to androgen deprivation. Physically mature male mice containing an inducible muscle specific SIRT1 transgene (SIRT1) were subjected to a sham or castration surgery and compared to sham and castrated male mice where the SIRT1 transgene was not induced (WT). The respiratory exchange ratio (RER), energy expenditure, and carbohydrate and fat oxidation rates were determined using metabolic cages. Castration lowered RER in WT mice and the lower RER coincided with lower energy expenditure, lower carbohydrate oxidation rates, and higher fat oxidation rates. SIRT1 induction attenuated the castration-induced changes to RER and fat oxidation rates. Changes to energy expenditure and glucose oxidation rates were not affected by SIRT1. Decreases in muscle SIRT1 protein in males may partially contribute to the dysregulation of whole-body metabolism in response to androgen deprivation.

Evaluation of the nephroprotective properties of silver nanoparticles formulated by Pistacia atlantica aqueous extract under ultrasonic condition in streptozotocin-induced diabetic nephropathy in mice

Green formulated silver nanoparticles offer a great promise in biomedicine. Administration of streptozotocin causes severe hepatotoxicity and nephrotoxicity by increasing the blood glucose. The development of nephroprotective drugs through eco-friendly production routes is a major challenge for current pharmacology and nanotechnology. The creation of cutting-edge technology for the synthesis of effective nephroprotective agents is crucial on a global scale. So in the current study, we report herein the bio-inspired proficient preparation of silver NPs over Pistacia atlantica (P.a.) aqueous extract as natural reducing/capping and stabilizing agent (P.a./Ag NPs) under ultrasonic irradiation. The final hybrid nanocomposite was thereafter characterized by a range advanced analytical methods like, FE-SEM, ICP-OES, EDX, TEM, and elemental mapping. Diabetes was induced by administration of 60 mg/kg of streptozotocin (STZ) intraperitoneally in 100 mature male mice and they were randomly divided into 5 groups. The negative control group received normal saline and treatment groups received glibenclamide with dose 0.5 mg/kg and 10 and 40 μg/kg of P.a./Ag nanocomposite through gavage for 50 days. On the last day, serum levels of samples blood glucose, urea and creatinine were measured. After tissue processing, 5 μm sections of the kidneys were prepared and they were stained by periodic acid Schiff (PAS) and used for stereological analysis. The kidney weight, kidney volume (Volume of cortex, medulla, glomerulus, proximal and distal tubules, collecting ducts, loop of Henle, interstitial tissues, and vessels) and kidney structures length (length of proximal and distal tubules, collecting ducts, loop of Henle, and vessels) decreased significantly (p ≤ 0.05) after treatment with high dose of P.a./Ag NPs nanocomposite (p > 0.05). The increased levels of blood glucose and urea were decreased (p ≤ 0.05) significantly in P.a./Ag nanocomposite-treated groups as compared to the untreated diabetic. This study suggested using from P.a./Ag nanocomposite as an antidiabetic and nephroprotective drug in the developing countries.

Tonic Activation of NR2D-Containing NMDARs Exacerbates Dopaminergic Neuronal Loss in MPTP-Injected Parkinsonian Mice.

NR2D subunit-containing NMDA receptors (NMDARs) gradually disappear during brain maturation but can be recruited by pathophysiological stimuli in the adult brain. Here, we report that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication recruited NR2D subunit-containing NMDARs that generated an Mg2+-resistant tonic NMDA current (INMDA) in dopaminergic (DA) neurons in the midbrain of mature male mice. MPTP selectively generated an Mg2+-resistant tonic INMDA in DA neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Consistently, MPTP increased NR2D but not NR2B expression in the midbrain regions. Pharmacological or genetic NR2D interventions abolished the generation of Mg2+-resistant tonic INMDA in SNpc DA neurons, and thus attenuated subsequent DA neuronal loss and gait deficits in MPTP-treated mice. These results show that extrasynaptic NR2D recruitment generates Mg2+-resistant tonic INMDA and exacerbates DA neuronal loss, thus contributing to MPTP-induced Parkinsonism. The state-dependent NR2D recruitment could be a novel therapeutic target for mitigating cell type-specific neuronal death in neurodegenerative diseases.SIGNIFICANCE STATEMENT NR2D subunit-containing NMDA receptors (NMDARs) are widely expressed in the brain during late embryonic and early postnatal development, and then downregulated during brain maturation and preserved at low levels in a few regions of the adult brain. Certain stimuli can recruit NR2D subunits to generate tonic persistent NMDAR currents in nondepolarized neurons in the mature brain. Our results show that MPTP intoxication recruits NR2D subunits in midbrain dopaminergic (DA) neurons, which leads to tonic NMDAR current-promoting dopaminergic neuronal death and consequent abnormal gait behavior in the MPTP mouse model of Parkinson's disease (PD). This is the first study to indicate that extrasynaptic NR2D recruitment could be a target for preventing neuronal death in neurodegenerative diseases.

SIRT1 induction in the skeletal muscle of male mice partially preserves limb muscle mass but not contractile force in response to androgen deprivation.

In males, the factors that decrease limb muscle mass and strength in response to androgen deprivation are largely unknown. Sirtuin1 (SIRT1) protein levels are lower in the limb muscle of male mice subjected to androgen deprivation. The present study aimed to assess whether SIRT1 induction preserved limb muscle mass and force production in response to androgen deprivation. Physically mature male mice containing an inducible muscle-specific SIRT1 transgene were subjected to a sham or castration surgery and compared to sham and castrated male mice where the SIRT1 transgene was not induced. SIRT1 induction partially preserved whole-body lean mass, tibialis anterior (TA) mass and triceps surae muscle mass in response to castration. Further analysis of the TA muscle showed that muscle-specific SIRT1 induction partially preserved limb muscle soluble protein content and fibre cross-sectional area. Unilateral AAV9-mediated SIRT1 induction in the TA muscle showed that SIRT1 partially preserved mass by acting directly in the muscle. Despite those positive outcomes to limb muscle morphology, muscle-specific SIRT1 induction did not preserve the force generating capacity of the TA or triceps surae muscles. Interestingly, SIRT1 induction in females did not alter limb muscle mass or limb muscle strength even though females have naturally low androgen levels. SIRT1 also did not alter the androgen-mediated increase in limb muscle mass or strength in females. In all, these data suggest that decreases in SIRT1 protein in the limb muscle of males may partially contribute to the loss of limb muscle mass in response to androgen deprivation. KEY POINTS: SIRT1 induction in skeletal muscle of male mice subjected to androgen deprivation partially preserved limb muscle mass and fibre cross-sectional area. SIRT1 induction in skeletal muscle of male mice subjected to androgen deprivation did not prevent preserve limb muscle force generating capacity. SIRT1 induction in skeletal muscle of females did not alter baseline limb muscle mass, nor did it affect the androgen-mediated increase in limb muscle mass.

Galactic Cosmic Irradiation Alters Acute and Delayed Species-Typical Behavior in Male and Female Mice.

Exposure to space galactic cosmic radiation is a principal consideration for deep space missions. While the effects of space irradiation on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Cognitive health implications put humans and missions at risk, and with the upcoming Artemis missions in which female crew will play a major role, advance critical analysis of the neurological and performance responses of male and female rodents to space radiation is vital. Here, we tested the hypothesis that simulated Galactic Cosmic Radiation (GCRSim) exposure disrupts species-typical behavior in mice, including burrowing, rearing, grooming, and nest-building that depend upon hippocampal and medial prefrontal cortex circuitry. Behavior comprises a remarkably well-integrated representation of the biology of the whole animal that informs overall neural and physiological status, revealing functional impairment. We conducted a systematic dose-response analysis of mature (6-month-old) male and female mice exposed to either 5, 15, or 50 cGy 5-ion GCRSim (H, Si, He, O, Fe) at the NASA Space Radiation Laboratory (NSRL). Behavioral performance was evaluated at 72 h (acute) and 91-days (delayed) postradiation exposure. Specifically, species-typical behavior patterns comprising burrowing, rearing, and grooming as well as nest building were analyzed. A Neuroscore test battery (spontaneous activity, proprioception, vibrissae touch, limb symmetry, lateral turning, forelimb outstretching, and climbing) was performed at the acute timepoint to investigate early sensorimotor deficits postirradiation exposure. Nest construction, a measure of neurological and organizational function in rodents, was evaluated using a five-stage Likert scale 'Deacon' score that ranged from 1 (a low score where the Nestlet is untouched) to 5 (a high score where the Nestlet is completely shredded and shaped into a nest). Differential acute responses were observed in females relative to males with respect to species-typical behavior following 15 cGy exposure while delayed responses were observed in female grooming following 50 cGy exposure. Significant sex differences were observed at both timepoints in nest building. No deficits in sensorimotor behavior were observed via the Neuroscore. This study revealed subtle, sexually dimorphic GCRSim exposure effects on mouse behavior. Our analysis provides a clearer understanding of GCR dose effects on species typical, sensorimotor and organizational behaviors at acute and delayed timeframes postirradiation, thereby setting the stage for the identification of underlying cellular and molecular events.

Evaluation of Flurbiprofen's anticonvulsant properties in pilocarpine-induced convulsions in mice

Background: Flurbiprofen is a nonsteroidal anti-inflammatory drug, it has non-selective COX inhibition properties, some NSAIDS has an anticonvulsant effect and benefit as an analgesic in seizure patient.
 Objective: we aimed to evaluate the possible anticonvulsant effect of flurbiprofen in mice.
 Methods: We used 25 mature male mice for our study, the mice were divided into five groups, then to prevent peripheral cholinergic activation, mice in all groups were injected intraperitoneally with atropine sulphate (1 mg/kg) subcutaneously one hour after dosing. Seizures were induced ten minutes later with a 300 mg/kg i.p. injection of pilocarpine. After the pilocarpine injection, the animals were monitored for 1 hour. seizures severity was tested by the Racine scale.
 Results: flurbiprofen at 0, 10, 20 and 40 mg/kg orally causes a significant decrease in the onset of convulsion and a considerable decrease in the duration of convulsion in comparison with the control group. Flurbiprofen at 20 and 40 mg/kg orally inhibited seizure scores in pilocarpine-treated mice in a dose-dependent manner. High-dose of flurbiprofen (40 mg/kg) significantly reduced seizure scores, similar to diazepam.
 Conclusion: flurbiprofen has potential anticonvulsant properties in mice models, further study must be conducted to assess the primary mechanism of action.

Evaluation of the anticonvulsant properties of flurbiprofen in pilocarpine-induced convulsions in mice

Background and objective: Flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), possesses non-selective COX inhibition properties. Some NSAIDs exhibit anticonvulsant effects and provide analgesic benefits for seizure patients. This study aimed to assess the potential anticonvulsant action of flurbiprofen in mice. Methods: Twenty-five mature male mice were divided into five groups for the study. To prevent peripheral cholinergic activation, mice in each group were injected intraperitoneally with atropine sulfate (1 mg/kg) subcutaneously one hour after dosing. Seizures were induced ten minutes later using an intraperitoneal injection of 300 mg/kg of pilocarpine. Following pilocarpine injection, the animals were monitored for 1 hour. Seizure severity was assessed using the Racine scale. Results: Oral administration of flurbiprofen at doses of 0, 10, 20, and 40 mg/kg resulted in a significant decrease in convulsion onset and a substantial reduction in convulsion duration compared to the control group. Flurbiprofen at 20 and 40 mg/kg inhibited seizure scores in pilocarpine-injected mice in a dose-dependent manner. A high dose of flurbiprofen (40 mg/kg) significantly reduced the duration of convulsions, delayed convulsion onset, and decreased seizure scores in mice (p <0.05). Conclusions: Flurbiprofen exhibits significant dose-dependent anticonvulsant activity. Further studies are necessary to determine the primary mechanism of action.

Generation of functional oocytes from male mice in vitro.

Sex chromosome disorders severely compromise gametogenesis in both males and females. In oogenesis, the presence of an additional Y chromosome or the loss of an X chromosome disturbs the robust production of oocytes1-5. Here we efficiently converted the XY chromosome set to XX without an additional Y chromosome in mouse pluripotent stem (PS) cells. In addition, this chromosomal alteration successfully eradicated trisomy 16, a model of Down's syndrome, in PS cells. Artificially produced euploid XX PS cells differentiated into mature oocytes in culture with similar efficiency to native XX PS cells. Using this method, we differentiated induced pluripotent stem cells from the tail of a sexually mature male mouse into fully potent oocytes, which gave rise to offspring after fertilization. This study provides insights that could ameliorate infertility caused by sex chromosome or autosomal disorders, and opens the possibility of bipaternal reproduction.