Thyroid hormone deficiency affects anxiety-related behaviors and expression of hippocampal glutamate transporters in male congenital hypothyroid rat offspring.

Thyroid hormones are crucial for brain development and their deficiency during fetal and postnatal periods can lead to mood and cognitive disorders. We aimed to examine the consequences of thyroid hormone deficiency on anxiety-related behaviors and protein expression of hippocampal glutamate transporters in congenital hypothyroid male offspring rats. Possible beneficial effects of treadmill exercise have also been examined. Congenital hypothyroidism was induced by adding propylthiouracil (PTU) to drinking water of pregnant Wistar rats from gestational day 6 until the end of the weaning period (postnatal day 28). Next, following 4 weeks of treadmill exercise (5 days per week), anxiety-related behaviors were examined using elevated plus maze (EPM) and light/dark box tests. Thereafter, protein expression of astrocytic (GLAST and GLT-1) and neuronal (EAAC1) glutamate transporters were measured in the hippocampus by immunoblotting. Hypothyroid rats showed decreased anxiety-like behavior, as measured by longer time spent in the open arms of the EPM and in the light area of the light/dark box, compared to control rats. Hypothyroid rats had significantly higher GLAST and GLT-1 and lower EAAC1 protein levels in the hippocampus than did the euthyroid rats. Following exercise, anxiety levels decreased in the euthyroid group while protein expression of EAAC1 increased and returned to normal levels in the hypothyroid group. Our findings indicate that thyroid hormone deficiency was associated with alterations in protein expression of glutamate transporters in the hippocampus. Up-regulation of hippocampal GLAST and GLT-1 could be at least one of the mechanisms associated with the anxiolytic effects of congenital hypothyroidism.

Bone marrow stromal cell-conditioned medium regenerates injured sciatic nerve by increasing expression of MPZ and NGF and decreasing apoptosis.

Objectives: Despite the many benefits of mesenchymal stem cell (MSC) transplantation for tissue regeneration, there are some limitations to using them, including the high costs, applying invasive procedures, the possibility of transplant rejection, and cell malignancy. This study aimed to investigate the effect of secretions of bone marrow stromal cells (BMSCs) with the cell-free strategy on damaged sciatic nerve with an emphasis on the role of apoptosis and the expression of myelin protein zero (MPZ) and nerve growth factor (NGF) proteins. Materials and Methods: BMSCs were cultured and a 25-fold concentrated conditioned medium (CM) from the cells was provided. After creating a crush injury in the left sciatic nerve of male rats, BMSCs or CM were injected into the injured site of the nerve. Four weeks later, the expression of MPZ, NGF, Bax, and Bcl-2 proteins in the sciatic nerve and histological parameters of the sciatic nerve and gastrocnemius muscle were assessed. Results: The results demonstrated that injection of CM decreased apoptosis and increased expression of MPZ and NGF proteins, improving remyelination and regeneration of the sciatic nerve almost as much as the transplantation of the BMSCs themselves compared to the control group. Conclusion: The results suggest that BMSC secretions may improve remyelination and regeneration of damaged sciatic nerve by increasing the expression of MPZ and NGF and decreasing apoptosis.

Bisphenol-S Influence on Oxidative Stress and Endocrine Biomarkers of Reproductive System: A Systematic Review and Meta-Analysis.

Background: Bisphenol-S (BPS), as a new human public health concern, was introduced to the plastic industry by BPA-free labeled products following the restrictions of Bisphenol-A (BPA) as a safe alternative. However, recent research has revealed a controversial issue. In this regard, the present study aimed to review the relationship between BPS exposure and reproductive system dis/malfunction. Methods: PubMed and other databases were searched up to January 2021. The standard mean difference (SMD) with a 95% confidence interval (CI) was calculated for the main parameters using the random-effects model. Finally, 12 studies with 420 subjects were included in this research. Forest plot, meta-regression, and non-linear dose-response effect were calculated for each parameter by random-effects model. Results: Based on the results of in vitro assessment, a significant increase was found in the oxidative stress parameters, including superoxide dismutase (SMD: 0.63, 95% CI: 0.321, 0.939), thiobarbituric acid reactive substances (SMD: 0.760, 95% CI: 0.423, 1.096), and reactive oxygen species (SMD: 0.484, 95% CI: 0.132, 0.835). In addition, the hormonal assessment revealed a significant decrease in male testosterone concertation (SMD: -0.476, 95% CI: -0.881, -0.071). Moreover, in vivo examination revealed a significant decrease in hormonal parameters, such as female testosterone (SMD: -0.808, 95% CI: -1.149, -0.467), female estrogen (SMD: -2.608, 95% CI: -4.588, -0.628), female luteinizing hormone (SMD: -0.386, 95% CI: -0.682, -0.089), and female follicle-stimulating hormone (FSH) (SMD: -0.418, 95% CI: -0.716, -0.119). Besides, linear and non-linear correlations were detected in the main parameters. Conclusion: In conclusion, based on the current meta-analysis, BPS was suggested to be toxic for the reproductive system, similar to the other bisphenols. Moreover, a possible correlation was indicated between oxidative and hormonal status disruption induced by BPS in male and female reproductive systems dis/malfunction.

Effects of diverse Types of Toxoplasma gondii on the outcome of Alzheimer's disease in the rat model.

Toxoplasma gondii has lifelong persistence in the brain and its cysts can affect gene expression and change diverse biological functions of neurons. Many studies indicated T. gondii infection as a risk factor for the development of behavioral changes and neurodegenerative diseases such as Alzheimer's disease (AD), although the etiopathogenetic link between them has not been exactly elucidated. The current study aimed to examine the effects of chronic toxoplasmosis infection with Types I, II, and III strains (RH, PRU, and VEG) alone and in combination on cognitive impairments and neuronal death in the Aß1-42-induced rat model of Alzheimer's disease. In the chronic toxoplasmosis phase, Alzheimer's induction was conducted by injecting Aß1-42 oligomers into the rat brain hippocampus. Behavioral tests were conducted 10 days after the AD induction. Real-time PCR was performed to evaluate T. gondii parasite burden by amplification of the B1 gene. Cytokines IL-1ß, TNF-α, and IL-10 were assayed in brain tissue supernatant using ELISA. Also, histopathological examinations were conducted to calculate inflammatory changes and neuronal death in the brain. Our findings showed that chronic toxoplasmosis infection with PRU reduces cognitive disorders, while the RH strain of T. gondii plays a destructive role and aggravates cognitive impairments in AD. Also, infection with a combination of PRU and VEG strains significantly improved spatial learning and memory impairments in Alzheimer's rat model. Histopathological findings also confirmed the results of behavioral tests, so that in AßPRU and AßPRU + VEG groups, neuronal death and infiltration of inflammatory cells were negligible and significantly less than in Alzheimer's and AßRH groups. Our findings indicate that chronic toxoplasmosis infection with PRU strain alone, also in combination with VEG strain can significantly improve cognitive disorders in AD rats, while RH strain plays a destructive role in AD pathogenesis.

Effect of sesamol on damaged peripheral nerves: Evaluation of functional, histological, molecular, and oxidative stress parameters.

Objective: Peripheral nerve injury is a clinical problem that may cause sensory and motor inabilities. Sesamol is an antioxidant that can help in repairing damaged central nervous system (CNS) and other organs. The present study aimed to investigate whether the antioxidant effects of sesamol could improve the function, structure, and myelination in rats' damaged peripheral nervous system (PNS). Materials and Methods: In this study, 28 adult male Wistar rats were randomly divided into four groups. In the sham group, the sciatic nerve was exposed and restored to its place without inducing crush injury. The control received DMSO (solvent) and the two experimental groups received 50 or 100 mg/kg sesamol intraperitoneally for 28 days after sciatic nerve crush injury, respectively. Next, sciatic function index (SFI), superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, expression of nerve growth factor (NGF) and myelin protein zero (MPZ) proteins in the sciatic nerve, and histological indices of the sciatic nerve and gastrocnemius muscle were evaluated. Results: The results showed that sesamol reduced oxidative stress parameters, increased expression of NGF and MPZ proteins, and improved function and regeneration of the damaged sciatic nerve. Furthermore, a significant regeneration was observed in the gastrocnemius muscle after treatment with sesamol. Although administration of both doses of sesamol was useful, the 100 mg/kg dose was more effective than the 50 mg/kg one. Conclusion: The results suggest that sesamol may be effective in improving damaged peripheral nerves in rats by reducing oxidative stress and increasing the expression of NGF and MPZ proteins.

Protective effects of treadmill exercise on apoptotic neuronal damage and astrocyte activation in ovariectomized and/or diabetic rat prefrontal cortex: molecular and histological aspects.

OBJECTIVE: Both estrogen deprivation and diabetes mellitus are known as risk factors for neuronal damage. Using an animal model of ovariectomized and/or streptozotocin (STZ)-induced diabetes mellitus, we examined expression of apoptosis-related proteins, neuronal damage, and astrocyte activation in prefrontal cortex of rats with/without treadmill exercise. METHODS: Adult female Wistar rats were divided into control, ovariectomized (Ovx, bilateral ovariectomy), diabetic (Dia, STZ 60 mg/kg; i.p.), and ovariectomized diabetic (Ovx + Dia) groups. Next, animals in each group were randomly subdivided into non-exercise and exercise subgroups. Animals in the exercise groups underwent moderate treadmill running for 4 weeks (5 days/week). Thereafter, expression of Bax, Bcl-2, and caspase-3, as apoptosis-related proteins, number of neurons, and number of glial fibrillary acidic protein (GFAP)-positive cells in prefrontal cortex were measured using immunoblotting, cresyl violet staining, and immunohistochemistry, respectively. RESULTS: In both Dia and Ovx + Dia groups, Bax and caspase-3 protein levels and number of GFAP-positive cells were higher than those in the control group, while Bcl-2 protein level and number of neurons compared were lower than the control group. Beneficial effects of exercise to prevent apoptosis-mediated neuronal damage and astrocyte activation were also observed in the Dia group. CONCLUSION: Based on our results, physical exercise could be beneficial to attenuate diabetes-induced neuronal damage in the prefrontal cortex via inhibition of apoptosis.

Neuroprotective Effects of Treadmill Exercise in Hippocampus of Ovariectomized and Diabetic Rats.

To determine detrimental effects of estrogen and insulin deficiencies on hippocampus, we examined apoptosis-induced neuronal damage and cholinergic system in ovariectomized and/or diabetic rat hippocampus. Possible neuroprotective effects of treadmill exercise were also investigated. Adult female Wistar rats were randomly divided into four groups (n = 5 rats/group) as follows: control, ovariectomized (Ovx), diabetic (Dia, streptozotocin (STZ) 60 mg/kg; i.p.), and Ovx + Dia groups. Each group was further subdivided into exercise and non-exercise groups. Animals in exercise groups were subjected to treadmill training, while those in non-exercise groups were placed on the stationary treadmill for 4 weeks (5 days/week). Apoptosis-related protein levels (i.e. Bax, Bcl-2, and caspase-3), number of survived neurons, and acetylcholinesterase (AChE) activity in the hippocampus were measured using Western blotting, Cresyl Violet staining, and Ellman assay, respectively. Both ovariectomy and diabetes increased expression of Bax and caspase-3 and decreased expression of Bcl-2 at protein levels. In addition, a significant decrease in the number of survived neurons was observed in both Ovx and Dia groups, while AChE activity was lower only in the Dia group. The Ovx + Dia group showed stronger apoptosis-induced neuropathology and inhibition of AChE activity. Treadmill exercise attenuated apoptosis-induced neuropathology in the Ovx and Dia groups and recovered AChE activity in the Dia group. Neuroprotective effects of treadmill exercise were mediated by inhibition of apoptosis. Moderate exercise protocol had no beneficial anti-apoptotic and neuroprotective effects in ovariectomized-diabetic rats.

Treatment of mouse cumulus-oocyte complexes with L-carnitine during vitrification and in vitro maturation affects maturation and embryonic developmental rate after parthenogenetic activation.

The technique of oocyte vitrification remains a challenge in most animal species. The present study aimed to evaluate the effects of cumulus cell presence and L-carnitine (LC) treatment during vitrification of selected immature oocytes by brilliant cresyl blue (BCB) staining on maturation and embryonic developmental rate after parthenogenetic activation. Immature oocytes were obtained from C57BL/6 female mice ovaries and stained with BCB. The BCB+ cumulus-oocyte complexes (COCs) were then selected and random parts of COCs were denuded from cumulus cells (denuded oocytes: DOs). COCs and DOs were treated with/out LC (0.6 mg/ml) during vitrification and in vitro maturation (IVM) procedures. A number of non-vitrified COCs were also treated with LC during the IVM process (fresh group). Maturation rate, intracellular glutathione (GSH) contents, and developmental competence of oocytes were also examined. The GSH levels in vitrified DOs+LC and vitrified COCs+LC groups were significantly higher (p < 0.01) than untreated vitrified-warmed COCs and DOs. Maturation rate and blastocyst developmental rate were reduced after the vitrification-warming procedure compared with the fresh group. The vitrified COCs+LC group showed a higher percentage of mature oocytes and the ability to develop to blastocyst stage than the vitrified-warmed DOs group (p < 0.01). These data indicated that the presence of cumulus cells around the competent oocyte and LC treatment during vitrification and IVM procedure could improve parthenogenetic developmental competence of vitrified-warmed oocytes by increasing GSH levels and accelerating oocyte maturation.

Apoptosis is involved in paraoxon-induced histological changes in rat cerebellum.

Acute toxicity of organophosphorus compounds is primarily caused by inhibition of acetylcholinesterase (AChE) at cholinergic synapses. The current study was designed to investigate the effects of paraoxon on histological changes as well as the role of mitochondrion-dependent apoptosis in causing this damage in the rat cerebellum. Adult male Wistar rats were intraperitoneally injected with paraoxon at 0.3, 0.7, or 1 mg/kg. Control animals were injected with corn oil as a vehicle. At 14 or 28 days after intoxication, histological changes and alterations in the expression of apoptosis-related proteins, including Bax, Bcl-2, and caspase-3, were investigated in the cerebellum using cresyl violet staining and western blotting, respectively. Findings showed the decreased thickness of both molecular and granular layers and reduction in the number of Purkinje cells in animals treated with a higher convulsive dose of paraoxon (1 mg/kg). In addition, exposure of rats to 1 mg/kg of paraoxon activated apoptosis pathway confirmed by an increase in Bax and caspase-3 and a decrease in Bcl-2 protein levels. According to our results, cerebellar histological changes and alterations in the expression of apoptosis-related proteins occur following exposure to a high convulsive dose of paraoxon and persist for a long time.

Effects of treadmill exercise on cognitive functions and anxiety-related behaviors in ovariectomized diabetic rats.

Diabetes mellitus and ovarian hormone deficiency are associated with mood and cognition disorders. We aimed to study the possible beneficial effects of treadmill exercise on cognitive impairments and anxiety-related behaviors in ovariectomized diabetic rats. Fourteen days after bilateral ovariectomy or sham operation, adult female Wistar rats (n = 7 per group) received an intraperitoneal injection of streptozotocin (60 mg/kg) for induction of diabetes mellitus or citrate buffer. After 14 days, the animals were subjected to treadmill running or placed on the stationary treadmill for 4 weeks (5 days/week). The animals were then subjected to Morris water maze (MWM), elevated plus maze (EPM), and open field test to determine spatial learning and memory, anxiety-related behaviors, and locomotor activity, respectively. Spatial learning decreased in diabetic and ovariectomized + diabetic (Ovx + Dia) groups. Decreased spatial memory and increased anxiety levels were observed in the Ovx, Dia, and Ovx + Dia groups. Animals in the Ovx + Dia group showed reduced locomotor activity. Treadmill exercise improved spatial memory and anxiety levels in the Ovx and Dia groups, while had no significant effect on spatial learning and memory, anxiety levels, and locomotor activity in the Ovx + Dia group. Collectively, our results showed that physical exercise has beneficial effects on anxiety-related behaviors and spatial memory, but not of learning, in the ovariectomized and diabetic animals. Co-existence of ovariectomy and diabetes exacerbates anxiety-related behaviors, but not cognitive functions, compared to diabetes or ovariectomy alone; these complications could not be improved by exercise.

Paraoxon-induced damage in rat hippocampus is associated with alterations in the expression of apoptosis-related proteins.

To determine the possible role of apoptosis in the development of paraoxon-induced brain damage, we evaluated expression of apoptosis-related proteins, the extent of neuronal damage, and activation of astrocytes in rat hippocampus. Adult male Wistar rats were intraperitoneally injected with one of three doses of paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle). After 14 or 28 days, expression of apoptosis-related proteins, including B-cell leukemia/lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), and caspase-3, as well as the number of neurons and glial fibrillary acidic protein (GFAP) positive cells in hippocampus were examined by western blot, cresyl blue staining, and immunohistochemistry, respectively. After 14 and 28 days, Bax and caspase-3 proteins were significantly increased in rats receiving 0.7 and 1 mg/kg of paraoxon. A significant decrease in Bcl-2 protein levels was also observed in 0.7 and 1 mg/kg groups after 14 days and in 1 mg/kg group after 28 days. Animals treated with 1 mg/kg of paraoxon showed a significant decrease in the number of neurons in the CA1 area. Also, those treated with 0.7 and 1 mg/kg of paraoxon showed an increase in the number of GFAP positive cells in both CA1 and CA3 areas as well as a significant decrease in survived neurons in the CA3 area. Our results indicated that neuronal damage induced by convulsive doses of paraoxon in rat hippocampus is mediated in part through apoptosis mechanism. Activation of astrocytes might lead to reduced extent of damage and damage and consequently increased neuronal survival.

Acrosome and chromatin integrity, oxidative stress, and expression of apoptosis-related genes in cryopreserved mouse epididymal spermatozoa treated with L-Carnitine.

Oxidative stress is believed to be an important cause of sperm damage during freezing. l-Carnitine (LC) may have the potential to improve sperm quality after frozen-thawed process. The present study aimed to investigate the effect of LC supplementation in cryoprotectant media of mouse epididymal sperm on post-thaw sperm quality and expression of apoptosis-related genes. Male BALB/cJ mice spermatozoa were cryopreserved in a cryoprotectant medium containing 2.5 or 5 mM LC. The untreated group was cryopreserved with the cryoprotectant medium only. Six months following cryopreservation, the samples were thawed and sperm quality parameters, chromatin and acrosome integrity, reactive oxygen species (ROS) and glutathione (GSH) levels, mitochondrial activity, and mRNA expression of Bax and Bcl-2 were assessed. The results demonstrated that the concentration of 5 mM LC in cryoprotectant media exhibited higher values for the sperm quality parameters and integrity of chromatin and acrosome in post-thaw spermatozoa than those of the untreated group. Furthermore, sperm ROS levels decreased while GSH and mitochondrial activity levels increased in 5 mM LC group compared to those in the untreated group (P < 0.01). In 5 mM LC-treated group, Bax was down-regulated (P < 0.05) while Bcl-2 was up-regulated (P < 0.001) compared to the untreated group. Collectively, LC supplementation of cryoprotectant medium improved the quality of frozen-thawed mouse epididymal spermatozoa, as showed reduced ROS level and Bax expression as well as increased GSH, mitochondrial activity, and Bcl-2 expression.

Effects of Paraoxon Exposure on Expression of Apoptosis-Related Genes, Neuronal Survival, and Astrocyte Activation in Rat Prefrontal Cortex.

Paraoxon is the bioactive metabolite of organophosphate (OP) pesticide, parathion. This study aimed to evaluate the expression of apoptosis-related genes and histopathological changes in rat prefrontal cortex following exposure to three different doses of paraoxon. Paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle) were intraperitoneally injected to adult male Wistar rats. After 14 or 28 days, mRNA and protein levels of Bax, Bcl-2, and caspase-3 were measured in prefrontal cortex using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, respectively. In addition, neuronal injury and astrocyte activation were assessed using cresyl violet staining and glial fibrillary acidic protein (GFAP) immune-positive cells, respectively. Treatment with 0.7 and 1 mg/kg of paraoxon increased mRNA and protein levels of Bax and caspase-3 at 14 and 28 days post-exposure, while mRNA and protein levels of Bcl-2 decreased only in 1 mg/kg group after 14 days. Furthermore, a significant decrease in the number of neurons and a significant increase in the number of GFAP-positive cells were observed in rats receiving 0.7 and 1 mg/kg of paraoxon at both time points. Collectively, our results showed that apoptosis is a major mechanism for neuronal damage after exposure to paraoxon. Also, paraoxon-induced neuronal loss was correlated with activation of astrocytes. Since paraoxon-induced neuronal damage is closely related to convulsion, clinical management of convulsion could protect neuronal brain damage.

Anxiolytic activity of paraoxon is associated with alterations in rat brain glutamatergic system.

Exposure to organophosphate (OP) compounds leads to behavioral alterations. To determine whether paraoxon has effects on anxiety, anxiety-like behaviors were assessed in paraoxon-exposed rats. Protein expression of glutamate transporters has also been measured in hippocampus and prefrontal cortex. Three doses of paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle) were intraperitoneally injected to adult male rats. At 14 or 28 days after exposure, behavioral tests were done using elevated plus-maze (EPM) or open field tests. Thereafter, animals were sacrificed and both hippocampi and prefrontal cortices were extracted for cholinesterase assay and western blotting. Animals treated with convulsive doses of paraoxon (0.7 and 1 mg/kg) showed an increase in percentage of time spent in open arms and percentage of open arm entries in the EPM. In the open field test, an increase in the time spent in central area was observed in rats treated with the same doses of paraoxon. These effects of paraoxon were independent of any changes in locomotor activity. There was an increase in both astrocytic glutamate transporter proteins (GLAST and GLT-1) in the hippocampus of animals treated with 0.7 and 1 mg/kg of paraoxon. In the prefrontal cortex, protein levels of the GLAST and GLT-1 increased in 0.7 and decreased in 1 mg/kg groups. Only a significant decrease in EAAC1 protein was observed in the prefrontal cortex at 14 days following exposure to 1 mg/kg of paraoxon. Collectively, this study showed that exposure to convulsive doses of paraoxon induced anxiolytic-like behaviors in both behavioral tests. This effect may be attributed to alterations of glutamate transporter proteins in the rat hippocampus and prefrontal cortex.

Effect of Transplantation of Bone Marrow Stromal Cell- Conditioned Medium on Ovarian Function, Morphology and Cell Death in Cyclophosphamide-Treated Rats.

OBJECTIVES: Although stem cell transplantation has beneficial effects on tissue regeneration, but there are still problems such as high cost and safety issues. Since stem cell therapy is largely dependent on paracrine activity, in this study, utilization of transplantation of bone marrow stromal cells (BMSCs)-secretome instead of the cells, into damaged ovaries was evaluated to overcome the limitations of stem cell transplantation. MATERIALS AND METHODS: In this experimental study, BMSCs were cultured and 25-fold concentrated conditioned medium (CM) from BMSCs was prepared. Female rats were injected intraperitoneally with cyclophosphamide (CTX) for 14 days. Then, BMSCs and CM were individually transplanted into bilateral ovaries, and the ovaries were excised after four weeks of treatment. The follicle count was performed using hematoxylin and eosin (H and E) staining and the apoptotic cells were counted using TUNEL assay. Ovarian function was evaluated by monitoring the ability of ovulation and the levels of serum estradiol (E2) and follicle-stimulating hormone (FSH). RESULTS: Evaluation of the ovarian function and structure showed that results of secretome transplantation were almost similar to those of BMSCs transplantation and there was no significant differences between them. CONCLUSIONS: BMSCs-secretome is likely responsible for the therapeutic paracrine effect of BMSCs. Stem cellsecretome is expected to overcome the limitations of stem cell transplantation and become the basis of a novel therapy for ovarian damage.

Differential expression of glutamate transporters in cerebral cortex of paraoxon-treated rats.

Glutamatergic system is involved in pathological effects of organophosphorus (OP) compounds. We aimed to determine in vivo effects of paraoxon, the bioactive metabolite of parathion, on the expression of glutamate transporters as well as Bax and Bcl2 in rat cerebral cortex. Male Wistar rats received an intraperitoneal (i.p.) injection of one of three doses of paraoxon (0.3, 0.7, or 1mg/kg) or corn oil as vehicle (1ml/kg). After 4 or 18h, cerebral cortices were dissected out and used for quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot assays to measure mRNA and protein levels, respectively. The cortical glial glutamate transporters (GLAST and GLT-1) were up-regulated in animals treated with 0.7mg/kg of paraoxon, but down-regulated in 1mg/kg group. Neuronal glutamate transporter (EAAC1) was unchanged in 0.7mg/kg treated rats, while reduced in 1mg/kg group. No significant difference was found in the mRNA and protein expression of EAAC1 in animals intoxicated with 0.3mg/kg of paraoxon. Paraoxon (1mg/kg) resulted in an up-regulation of Bax and down-regulation of Bcl2 mRNA levels in the rat cerebral cortex. These results indicate that paraoxon can differentially regulate expression of glutamate transporters at mRNA and protein levels in the cerebral cortex. Changes in the expression of glutamate transporters are closely related to paraoxon-induced seizure activity.

Supplementation of L-carnitine during in vitro maturation of mouse oocytes affects expression of genes involved in oocyte and embryo competence: An experimental study.

BACKGROUND: Oocyte developmental competence is one of the key factors for determining the success rate of assisted reproductive technique. OBJECTIVE: The aim of the current study was to investigate the effect of L-carnitine (LC) supplementation during in vitro maturation (IVM), on preimplantation embryo development and expression of genes involved in embryo competence derived from oocytes selected with brilliant cresyl blue (BCB) test. MATERIALS AND METHODS: Cumulus-oocyte complexes (COCs) were obtained from NMRI mice ovaries. COCs were stained with BCB and then BCB+ (colored cytoplasm) oocytes cultured in IVM medium supplemented with 0.3 or 0.6 mg/ml LC. COCs untreated with LC were used as control. Fertilization rate and blastocyst development rate were determined after in vitro fertilization. In addition, quantitative reverse transcriptase polymerase chain reaction was used to measure relative genes expression related with development (Ccnb1, Mos, Ces5, and Dppa2) and apoptosis (Bax and Bcl-xL) in oocytes and embryos. RESULTS: Oocytes treated with both LC concentrations showed higher blastocyst development rate compared with untreated oocytes (p<0.01). Moreover, fertilization rate was increased in oocytes treated with 0.6 mg/ml LC (p<0.01). Treatment of oocytes with both LC concentrations increased (p<0.01) the level of Ccnb1 mRNA in MII oocytes. The two-cell stage embryos and blastocysts derived from LC-treated oocytes (0.6 mg/ml) showed increased the expression levels of Dppa2 and Bcl-xl mRNA, respectively (p<0.01). CONCLUSION: The results of the present study show that adding of LC to the IVM medium of BCB+ oocytes can ameliorate reproductive success following in vitro fertilization.

Comments on Quaak, et al. The Dynamics of Autism Spectrum Disorders: How Neurotoxic Compounds and Neurotransmitters Interact. Int. J. Environ. Res. Public Health 2013, 10, 3384-3408.

I have read the article entitled "The dynamics of autism spectrum disorders: how neurotoxic compounds and neurotransmitters interact". There are some errors in the interpretation of results obtained from our previous studies that should be explained.

Alterations in mRNA and protein expression of glutamate transporters in rat hippocampus after paraoxon exposure.

Organophosphates affect brain function through a variety of mechanisms beyond their shared role as cholinesterase inhibitors. The aim of the current study was to investigate the changes in the expression of glial (GLAST and GLT-1) and neuronal (EAAC1) glutamate transporters at mRNA and protein levels in paraoxon-treated rat hippocampus. Adult male Wistar rats were intraperitoneally treated with either vehicle (corn oil) or one of three dosages of paraoxon (0.3, 0.7 or 1mg/kg). After 4 or 18h, both hippocampi of each rat were collected to detect mRNA and protein expression of glutamate transporters using the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, respectively. Animals treated with 0.3mg/kg paraoxon showed no difference in mRNA and protein levels of the glutamate transporters when compared with control group. At 4h after exposure with 0.7 and 1mg/kg paraoxon, the expression of GLAST and GLT-1 increased at mRNA and protein levels and remained elevated after 18h. No difference in the expression of EAAC1 at mRNA and protein levels was observed in any paraoxon-treated groups compared with the control group. This study showed an increased expression of glial (GLAST and GLT-1), but not neuronal (EAAC1) glutamate transporters, in adult rat hippocampus following administration of convulsive dosages of paraoxon. These suggest a protective and compensatory adaptation for effective uptake of glutamate in hippocampus induced by paraoxon and thus attenuating seizure activity.

Prevalence of Asthma and Respiratory Symptoms among University Students in Sari (North of Iran).

BACKGROUND: Despite widely available data about childhood asthma, there are limited data about the prevalence of asthma among young adults in Iran. The aim of this study was to determine the prevalence of asthma and respiratory symptoms among medical students in the city of Sari in Northern Iran. MATERIALS AND METHODS: The prevalence of asthma and respiratory symptoms was studied using a standard questionnaire. Based on the information obtained from the questionnaires, the study participants were divided into two groups of asthmatics and non-asthmatics. Pulmonary function tests including forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) before, and after salbutamol inhalation were measured in all subjects with asthma and approximately 10% of those without asthma. RESULTS: A total of 1,011 subjects (374 males, 637 females) participated in this study. Asthma was found in 3.5% of the subjects (3.2% males and 3.6% females). The 12-month prevalence of wheezing, coughing at rest, coughing at night, breathlessness at rest, exercise-induced wheezing, and exercise-induced coughing in the entire study population was 11.1%, 12.4%, 13.4%, 13.3%, 17.7%, and 16.7%, respectively. The prevalence of all asthma-related symptoms was significantly higher among asthmatics compared to non-asthmatics. Moreover, asthmatic subjects showed lower FEV1 and FVC values compared to nonasthmatic subjects (P<0.001). Smoking and family history of asthma were statistically significant risk factors for developing asthma. CONCLUSION: The high prevalence of asthma related symptoms in the present study strongly suggests that asthma is under diagnosed and under treated among participants.