مجله فیزیولوژی و فارماکولوژی ایران
سال پنجم شماره 1 (پیاپی 15، بهار و تابستان 1400)

Musclin is a factor secreted by skeletal muscle and a potent regulator of glucose metabolism that responds to exercise. Therefore, exercise-induced musclin may contribute to the pathogenesis of diabetes. The aim of the present study was to evaluate the effects of musclin, exercise-induced myokine on glycosylated hemoglobin (HbA1c) of hyperlipidemic rats with type 1 diabetes.

Twenty-one male Wistar rats were divided into 3 groups of 7 rats per each: non-diabetic, diabetic and training diabetic. Type 1 diabetes was induced by injection of streptozotocin (55 mg/kg). After familiarization, training diabetic rats ran increasingly on a rodent treadmill for 4 weeks (5 consecutive days per week). After the 4-week period, serum glucose, insulin and musclin (using Elisa kit), and lipid profile (total cholesterol, triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol) were measured and HbA1c was determined. Data were analyzed by two-way analysis of variance.

Increased serum musclin in hyperlipidemic diabetic rats increased HbA1c compared to non-diabetic rats
(p < 0.05). After 4 weeks of exercise training, HbA1c decreased along with a decrease in serum musclin in hyperlipidemic diabetic rats (p < 0.05), so that a decrease in serum glucose and insulin in diabetic rats was associated with a improvement in lipid profile resulting in a decrease in HbA1c (p < 0.05).

Four weeks of aerobic training by regulating circulating musclin improved lipid profile and HbA1c in type 1 diabetes. Hence, musclin, exercise-induced myokine could decrease HbA1c in hyperlipidemic rats with type 1 diabetes.

The notion that non-genetic and non-cultural mechanisms can transmit the memory of exposure to diverse environmental conditions to subsequent generations has excited considerable interest and has brought the Lamarck’s idea back into the limelight. It is widely accepted that the environmental experiences of parents have strong effects on the physiological, metabolic, and cellular functions of living organisms, which are transmitted through epigenetic modifications to the next generations. The epigenetic modifications prone to change in environmental conditions and transmitted to next generations include DNA methylation, histone modification, and small non-coding RNAs. Currently, one of the most exciting topics in the field of epigenetic transmission is the transfer of memory phenotypes and learning and memory capabilities. Inheriting epigenetic traits allows living organisms to transmit compatible or incompatible information with the ancestral environment to their offspring. Studies showed that exposure to environmental stimuli by parents before fertilization would lead to changes in their childrenchr('39')s cognitive capacities. Interestingly, learning cognitive tasks in parents improved the learning and facilitated memory consolidation in offspring. The methylation DNA, histone methylation and histone acetylation are three major epigenetic processes involved in the regulation of learning and memory consolidation. These processes modify genome features or interactions between the genome and the histone nucleus, and then induce structural changes in chromatin, leading to transcriptional changes in various genes that affect memory formation. The transfer of these chromatin modifications from parents to offspring facilitates the offspring learning process and memory consolidation.

Salvia officinalis leaves and Cyperus rotundus rhizomes have a wide range of biological effects such as memory formation. Given to importance of herbal plants, in the present study we investigated effect of concomitant administration of ineffective doses of the extracts of Salvia officinalis leaves and Cyperus rotundus rhizomes on memory impairment induced by stress.

Adult male mice in two control and treatment groups received ineffective doses of the extracts of Salvia officinalis leaves and Cyperus rotundus rhizomes alone and together by gavage, for 7 or 21 days. Then animals received acute stress. Passive avoidance memory was evaluated by shuttle-box apparatus.

Acute stress significantly impaired memory. Neither Salvia officinalis extract nor Cyperus rotundus extract could improve memory alone. However, concurrent administration of the extracts improved destructive effect of acute stress on memory recall. Memory improving effect of the 21-days administration was significantly more than the effect of the 7-days administration.

Concurrent administration of the extracts of Salvia officinalis and Cyperus rotundus improves destructive effects of acute stress on passive avoidance memory in a time dependent manner.

Many organisms have rhythmic fluctuations in their physiological and behavioral functions, Known as circadian rhythms. Suprachiasmatic nucleus (SCN) of the hypothalamus is the central pacemaker, which synchronized these rhythms to the environmental light/dark cycle. The main factor in the regulation of circadian rhythms is the family of genes called clock genes. In addition to the suprachiasmatic nucleus, these genes are expressed in many areas of the body as well as different areas of the brain. The clock genes are expressed in addiction-related areas including the ventral tegmental area, the nucleus accumbens and the prefrontal cortex. Thus, it seems that these areas are also under the control of the circadian rhythm. Opioid addiction is a chronic physical and mental illness that remains a great threat to communities around the world. Investigations have been shown that many factors involved in opioid addiction such as orexin, dopamine, and serotonin, are regulated by circadian rhythms. Accordingly, in this review article, we will describe briefly some factors associated with circadian rhythms and opioid addiction.

Soluble amyloid beta (Aβ) oligomers are the most common forms of Aβ in early stage of Alzheimer disease (AD). They are highly toxic to the neurons, but their capability to activate microglia remains controversial. Synaptic function and memory performance are disrupted by soluble form of Aβ. Full and partial toll like receptor (TLR) ligands can stimulate microglia to produce different cytokine and chemokine profiles. This study was designed to investigate the expression of interlukin-6 (IL-6) as a cytokine and protein 10 interferon gamma (IP-10) as a chemokine from BV-2 microglia cell line in the presence and absence of Aβ.

The BV-2 cell line was cultured in a 24-well plate, treated for 24 h with different doses (0.1, 1, 10 µg) of Monophosphoryl lipid A (MPL), Lipopolysaccharide (LPS) as TLR4 ligands, and Pam3cys as a TLR2 ligand. Then supernatant was collected and cells were incubated with 1µM Aβ oligomer for 24 h. IL-6 and IP-10 expression was measured by ELISA in the supernatant before and after Aβ treatment.

LPS and Pam3cys 10µg/µl induced a robust release of IL-6 from BV-2 microglia cells. However, MPL at all doses had a lowest effect on secretion of IL-6 from BV-2 microglia cells. On the other hand, pretreatment of BV-2 cells with MPL as a partial TLR4 ligand caused release of significant amount of IP-10 chemokine from BV-2 cells.

It can be said that priming microglia to produce less pro-inflammatory cytokines while showing higher chemokine or phagocytic activity leads to decrease in Aβ deposition and might prevent AD progression.

Recent studies have shown Cinnamomum zeylanicum antioxidant/anti-inflammatory activities, and inhibition of tau accumulation and Amyloid beta (Aβ)   aggregation. Therefore, it seems that this plant can improve cognition in rat model of Alzheimer’s disease (AD). For this purpose, the ability of an aqueous extract of cinnamon in attenuating Aβ-induced learning impairment was evaluated in a rat model of AD.

Aβ-protein fragment 25-35 was injected into the CA1 region of rats’ hippocampus and the effect of different doses of cinnamon extract (5, 10, or 20 mg/kg) on cognitive function was assessed in the Morris water maze. Animals were subjected to 5 days of training; 4 days with the invisible platform to test spatial learning and the 5th day with the visible platform to test motivation and sensorimotor coordination.

The results showed an significant increase in escape latency, traveled distance, orientation angle and decrease in target quadrant entries in Aβ-received rats. Cinnamon extract was able to significantly reduce the effect of Aβ.

The results indicates learning and memory impairment in Aβ25-35 groups. These impairments were reversed by administration of Cinnamomum zeylanicum extract. Our results suggest that cinnamon may be a valuable agent for alleviating symptoms of Aβ.

Phytogenic compounds are a valuable and powerful source of effective compounds with diverse biological properties that some of which have good antiviral properties. Modifying the chemical structure of these compounds with computer-based simulations may increase their strength or effectiveness. Due to the great variety of plants, finding an effective plant compound against coronavirus is practically similar to "finding a needle in a haystack". So, considering previous studies on coronaviruses in animals can help in finding of effective plants and phytogenic compounds against SARS-CoV 2. In this study, 28 articles related to anti-coronavirus herbal treatments in animals were selected and analyzed by searching for keywords related to anti-coronavirus herbal treatments in PubMed database. Previous studies have shown that some of the key compounds have shown promising effects in the treatment of coronaviruses including curcumin, hesperidin, artemisinin, silosterol, cineole (eucalyptol), alstotide, lectins such as griffithsin, GNA (Galanthus nivalis agglutinin), lycorine and polyphenolics e.g. quercetin. Before conducting clinical trials in humans, in vitro and in vivo tests are needed to determine the level of immunity, safety, and therapeutic level for each compound. Preliminary studies may focus on compounds that have already been approved for pharmaceutical use or have been identified as safe compound. Researchers may use natural derivatives to produce safe and effective anti-coronavirus agents using the information presented in this review.

Morphine exerts some of its effects via gap junctions. In this study, the effect of blocking the electrical synapses of the dentate gyrus was evaluated on morphine state-dependent learning.

Male rats weighing 200-250g were used. The passive avoidance task was used to evaluate memory. Two guide cannulas were implanted in the dentate gyrus, stereotaxically. In an experiment, animals received different doses of morphine, post-training and 24 hours later memory retrieval was evaluated. In another experiment, animals received morphine (7.5 mg/kg), post-training. One day later, 30 min before the test, different doses of morphine was injected. In another experiment, animals received quinine (100µM, 1mM and 10mM) in the test day and 40 min later memory retrieval was evaluated. In the last experiment, animals were injected with morphine (7.5 mg/kg), post-training. In the test day, different doses of quinine and 10 min later morphine (7.5 mg/kg) were injected.

Post-training injection of morphine (0.5, 2.5, 5, 7.5 mg/kg) impaired memory retrieval dose-dependently. Also, morphine induced a state-dependent memory. Blocking the electrical synapses of the dentate gyrus did not prevent the development of morphine state-dependent memory.

It seems that closing of the electrical synapses of the dentate gyrus does not affect memory retrieval induced by morphine on the test day.

Endogenous opioids are responsible for diverse physiologic actions through activation of specific receptors. Acute consumption of opioids has no serious complication. Chronic use of opioids though is accompanied by tolerance to some effects (such as constipation, nausea and dry mouth), it leads to addiction and brain dysfunction. On the other hand, stopping the chronic use of opioids causes withdrawal signs (including sweating, anxiety, nausea, muscular pain, insomnia, diarrhea, agitation and hot flush) without get rid of psychological dependence. It is well known that exercise activities (EAs) are associated with euphoria and delight through activation and release of endogenous opioids. Therefore, EAs can be effective in prevention and treatment of addiction. Beta-endorphin is one the most important endogenous opioids. It is an endogen neuropeptide with narcotic properties that is found in central and peripheral nervous system. Despite numerous studies on the effects of EAs on beta-endorphin, understanding impact of the different types of EAs on beta-endorphin and other endogen opioids requires further studies. In this article acute and chronic effects of EAs on beta-endorphin are reviewed. It is well accepted that acute and chronic EAs increase beta-endorphin level. Mechanism(s) responsible for rising beta-endorphin after acute and chronic EAs are somewhat different.

Obesity leads to some chronic diseases. Adiponectin is an adipokine secreted by adipose tissue. Fibroblast 21 has anti-diabetic effects. On the other hand, Tribulus terrestris is a plant with anti-inflammatory and antioxidant activities. The aim of this study was to investigate the effect of intensity interval training (IIT) and consumption of T. terrestris supplement on fibroblast growth factor 21 and adiponectin in obese women.

In a quasi-experimental study, 40 obese women were randomly divided into four groups of 10 including IIT + placebo, T. terrestris supplement, IIT + T. terrestris supplement, and control. The training program was implemented for 8 weeks. The exercises were consisted of 7 repetitions of 20 seconds with an intensity of 85 to 100% of the stored heart rate. T. terrestris supplement was taken 500 mg twice per day for the training period.

IIT + T. terrestris increased serum levels of fibroblast 21 and adiponectin in volunteers. The difference between pre- and post-test fibroblast 21level was significant in IIT + placebo (p < 0.007), T. terrestris (p < 0.003), and IIT + T. terrestris (p < 0.0001) groups. The difference between pre- and post-test adiponectin level was also significant in IIT + placebo (p < 0.003), T. terrestris (p < 0.002) and IIT + T. terrestris (p < 0.0001). The IIT + T. terrestris group showed the most positive effect on increase of fibroblast growth factor 21 and adiponectin levels among the groups.

IIT along with consumption of T. terrestris supplement increases fibroblast growth factor 21 and adiponectin levels in obese women, and improves the obesity condition in these people.

The prevalence of metabolic disorders such as obesity and metabolic syndrome has increased with age. Resistin and visfatin are adipokines involved in metabolic regulation and physiological processes. Exercise is also known as a non-pharmacological method affecting health. The aim of this study was to evaluate the effect of 8 weeks circular resistance training on serum levels of resistin and visfatin in elderly women with metabolic syndrome.

In a quasi-experimental study, 18 elderly women with metabolic syndrome were randomly divided into two groups: resistance training with body weight (n = 9) and control (n = 9). The resistance training program with body weight consisted of 12 movements and was performed for 8 weeks and three sessions per week. Statistical analysis was performed using paired t-test.

In elderly women with metabolic syndrome, resistance training with body weight reduced serum levels of resistin by 34.7% (p = 0.004) compared to pre-test values ​​. The resistance training with body weight also reduced visfatin levels by 26.1% (p = 0.024). No significant difference was found in any of the indicators in the control group..

Eight weeks of resistance training reduced serum resistin and visfatin in elderly women with metabolic syndrome. The resistance training is suggested to be considered as a health improving factor in the elderly.

Addiction is a phenomenon that affects various aspects of individual, family and social life and causes many abnormalities. In today's society, the main concern is the increase in drug abuse among adolescents. Substance abuse has occurred in adolescents due to lack of awareness of the consequences of using these substances along with increasing their availability. There is not much information about the long-term effects of substance abuse during adolescence. According to human epidemiological evidence, adolescents with drug abuse are more likely to become addicted during adulthood. Although the mechanisms involved are not fully understood, it can be argued that physiological and behavioral differences between adolescents and adults are factors in initiating drug abuse during this period. Substance use during adolescence can have lasting effects throughout life. Animal studies have shown that exposure to substances such as alcohol, nicotine, opioids, cannabinoids, cocaine and methamphetamine can have lasting neurological and behavioral effects; In particular, these lasting effects are more common in areas of the brain that are developing during adolescence. In this article, we will discuss the findings of long-term changes due to drug abuse in adolescence on cognitive function during adulthood.

Various neurochemical pathways participate in regulating food intake in mammals and birds. The nociceptin/orphanin FQ ‎(N/OFQ) ‎is involved in the central nervous system and increass food intake. Nitric oxide (NO) is a hypophagic agent in birds. ‎The present study aimed to investigate the central nociceptin/orphanin FQ (N/OFQ) effects and its interaction with nitrergic systems on feeding behavior in neonatal chickens.

Seventy-two neonatal male broiler-type (Ross 308) chickens were divided randomly into two experimental groups. Each experiment had a control group and three treatment groups (n = 12). In all experiments, 3-hour food-deprived (FD3) birds received intracerebroventricular (ICV) ‎injections either diluent (control) or drug solution. Then the birds had ad libitum access to the ‎food and fresh water, and then cumulative food intake (g) was measured based on the ‎percentage of the body. In the first experiment, chickens received ICV injection of L-arginine (NO precursor, 400 nmol), N/‎OFQ (16 nmol), and L-arginine with N/OFQ. L-NAME (NO ‎synthase inhibitor, 200 nmol), N/OFQ (16 nmol), and L-NAME + N/‎OFQ were injected in the second experiment.‎

ICV injection of N/OFQ significantly increased food intake (p < 0.05). Injection of the N/OFQ + L-arginine significantly attenuated the hyperphagic effect induced by N/OFQ in neonatal broilers (p < 0.05). Conversely, injection of the N/OFQ + L-NAME significantly decreased the hyperphagic effect induced by N/OFQ (p < 0.05).

Our findings suggest that the hyperphagic effect of central N/OFQ ‎ in FD3 neonatal layer-type ‎chicken is probably mediated by nitric oxide.‎

Spinal cord injury is a debilitating neurological disease. Despite recent clinical advances in diagnostic methods and survival of patients, there are still challenges in the treatment of patients with SCI. This lack of appropriate treatment is mainly due to the complexity of physiopathology and the various biochemical changes in spinal cord injury. In recent decades, remarkable studies have been reported to identify the physiopathology of spinal cord injury and to discover the cellular and molecular mechanisms of tissue destruction and repair in the damaged spinal cord.  Various animal models have been used to study the primary and secondary phases of spinal cord injury and its progression. In this review, we discuss recent advances in understanding the physiopathology of spinal cord injury. We also describe the SCI animal models to define the mechanisms of spinal damage and the treatment strategies.

The aim of this study was to determine the effect of aerobic activity and vitamin E on spatial memory and CREB protein expression in the hippocampal tissue of young rats with chronic sleep restriction.

Fifty-six healthy adult male Albino-Wistar rats were randomly assigned into the groups. Chronic sleep restriction was applied through 18 hours of sleep deprivation for 4 weeks. Aerobic activity included 4 weeks of running on a treadmill. Vitamin E dissolved in sesame oil was fed to rats by gavage. At the end of the fourth week, the Morris Water Maze test was performed to measure spatial learning and memory. Western blotting technique was used to measure the expression of CREB protein in the hippocampus. Mixed analysis of variance (5 × 3) was used to analyze the data related to acquisition in the Morris Water Maze and one-way analysis of variance was used to analyze the data related to the probe of the Morris Water Maze and the expression of CREB protein. Bonferroni and Tukey post hoc tests were used for within- and between-group comparisons, respectively.

Chronic sleep restriction significantly impaired memory function during the acquisition phase and probe test as well as CREB expression (p < 0.05). Vitamin E had no significant effect on spatial memory and CREB protein expression in rats with chronic insomnia. Aerobic activity prevented the deleterious effects of chronic sleep restriction on memory function during the acquisition phase, probe test and the CREB protein expression (p < 0.05). Finally, vitamin E along with aerobic activity had a significant effect on the expression of CREB protein in chronic sleep restricted rats (p < 0.05) but in the behavioral test showed no greater effect than aerobic activity (p > 0.05).

It seems that a period of aerobic activity prevents the deleterious effect of sleep restriction on learning and memory impairment in rats. Vitamin E alone had no effect on memory impairment in sleep-deprived rats. Moreover, it did not increase the positive effects of aerobic activity on the memory impairment of the sleep-deprived rats.‎

Linalool is a monoterpenoid compound that is a major component of the essential oils of some aromatic plants, including lavender. The anxiolytic and sedative effects of this compound have been previously reported. In this study, the effect of systemic administration of linalool and its possible mechanism of action on pentobarbital-induced sleep in mice was investigated.

In the first phase of this study, twenty-four mice in 4 separate groups received linalool at the doses of 10, 50 and 100 mg/kg sixty minutes before pentobarbital administration. Based on the results of the first phase of the study, 50 mg/kg was determined as the effective dose of linalool. In the next step, for determination of the involved mechanism in linalool hypnotic activity, diazepam as a GABA benzodiazepine receptor agonist, flumazenil a GABA benzodiazepine receptor antagonist, and WAY100635 a serotonin receptor antagonist were used.

Linalool, especially at the dose of 50 mg/kg, significantly and dose-dependently affected pentobarbital-induced sleep by increasing sleep time and decreasing sleep latency. Co-administration of diazepam with linalool showed synergistic effects and increased sleep time; however, by flumazenil administration these effects were reversed. Administration of WAY100635 did not cause any effect on the increasing effect of linalool on pentobarbital-induced sleep.

Linalool may possibly be effective on pentobarbital-induced sleep through the GABAergic pathway.

Light pollution causes structural and functional changes of many organs, especially those with cyclic activity. Research on the effects of artificial light and light pollution on the sexual cycle and fertility of females is limited. In this study, the effects of light pollution on the sexual cycle and the structural-hormonal characteristics of the thyroid and adrenal glands of female rats are investigated.

Twenty one female rats with regular sexual cycle were divided into three groups as control (12 h light/12 h dark cycle), experimental 1 (16 h light/8 h dark cycle) and experimental 2 (20 h light/4 h dark cycle). Animals were exposed to light for 47 days and vaginal smear was examined daily. Then, the animals were mated with male rats. Pregnancy was confirmed by observing the vaginal plaque of pregnancy. The pregnant animals were kept in the light/dark cycle conditions until the 19th day of pregnancy. On the 19th day of pregnancy, rats were bled under deep anesthesia and serum levels of T4, thyroid stimulating hormone and cortisol were measured. Then, thyroid and adrenal glands were dissected out and morphologically examined.

In experimental groups 1 and 2, the sexual cycle became irregular and remained in the estrus stage in almost all rats. Compared with the control group, size of thyroid follicles decreased and the mean level of T4 hormone increased significantly (p < 0.05) in the experimental groups. Serum levels of thyroid-stimulating hormone and cortisol did not change, but the thickness of the fascicle area in the adrenal gland increased significantly (p < 0.05). 

The thyroid and adrenal glands of rats are sensitive to light pollution and their function is altered.‎

Studies suggest that early-life maternal sepration (MS) could induce cognitive impairments. One of the stress-modulating factors is enriched environment (EE), which provides more opportunities to explore the environment. Moreover, studies have been shown that oxytocin (OT) reduces stress effects on the rat brain. The aim of this study wass to evaluate EE and OT effects on passive avoidance learning and memory in maternally separated rats.

Eight groups were evaluated during this experiments; CTRL, CTRL + EE, MS, MS + EE, CTRL + saline, CTRL + OT, MS + saline, MS + OT. In MS group, rat pups were separated from their dam for 180 min/day from post natal day (PND) 1-21. From PND 22-34 rats experienced EE and/or received intranasal OT )2 µg/µl(. At adolescence, passive avoidance learning and memory of rats were evaluated in the shuttle box.

MS rats received more foot shocks compared to the CTRL rats. Moreover, in comparison to CTRL animals, the latency to enter the dark chamber decreased in MS rats. EE and OT could improve these MS-induced impairments.

 Obtained results showed that EE and OT could improve stress-induced cognitive impairments.‎

The body's antioxidant system, which is responsible for counteracting the damaging effects of free radicals, can be affected by various factors, including exercise. Nigella sativa is an anti-inflammatory and antioxidant plant. The aim of this study was to evaluate the short-term effect of intense aerobic exercise and supplementation of Nigella sativa on serum malondialdehyde and superoxide dismutase levels of young men.

In a quasi-experimental study, 28 young men were randomly divided into four groups of 7 including aerobic exercise + placebo, Nigella sativa supplement, aerobic exercise and Nigella sativa supplement and control. The Bruce aerobic exercise protocol for one-week, and 3 times/week was performed.

The serum malondialdehyde level between pretest and posttest in the exercise + placebo (p < 0.01), exercise + Nigella sativa supplement (p < 0.05) and Nigella sativa supplement (p < 0.05) was significant. There was a significant difference between the exercise + placebo group and the two other groups including exercise + supplement (p <0.001) and supplement (p < 0.001) groups. The serum superoxide dismutase between pretest and posttest in the exercise + placebo groups (p <0.05), exercise + Nigella sativa supplement (p < 0.05) and Nigella sativa supplement (p < 0.05), was significant. Compared to the exercise + placebo group, superoxide dismutase was significantly increased in the exercise + Nigella sativa (p < 0.001) and Nigella sativa (p < 0.001) groups.

It seems that after intense aerobic exercise, the antioxidant system is weakened and the use of antioxidant supplements such as Nigella sativa can strengthen the antioxidant defense against oxidative stress caused by intense exercise and ultimately increase antioxidant enzymes and decrease free radicals.‎

Glioblastoma multiforme is the most malignant and invasive primary brain tumor in adults. The disease has a poor prognosis with a survival rate of 14-16 months post diagnosis. Depending on the tumor location in the brain, a wide range of signs and symptoms may appear in the patient. One of the most common of which is recurrent hard to control seizures. Despite the high prevalence of tumor-induced seizures, the mechanisms involved in its occurrence are yet to be fully identified. However, it has been shown that glutamate and GABA are probably the major contributing factors. Increasing extracellular glutamate levels due to changes in the expression of ion transporters and the conversion of GABA to a stimulatory mediator are some of the mechanisms involved in the development of these seizures. In addition, factors such as the complex pathophysiology of the disease, its associated-seizures, drug interactions, resistance to treatment and tumor recurrence have made glioblastoma management a major challenge. In this article, the common clinical symptoms of this disease and in particular tumor-associated seizures are reviewed. The mechanisms thought to be responsible for the development of the tumor-induced seizures are then discussed.

Alzheimer's disease (AD) is the most common age-associated neurodegenerative disease with involvement of genetic factors. Recent studies have shown that the protein cystatin C binds soluble Aβ and inhibits Aβ oligomerization and amyloidogenesis, protecting the brain against amyloid-induced toxicity. Moreover, a decreased cystatin C secretion is associated with a polymorphism found in the cystatin C gene. In this study the association between rs1064039 polymorphism and late-onset AD was investigated.

We conducted a case-control study including a clinically well-defined group of 160 late-onset AD patients and 167 age-matched controls. The polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-PFLP) assay. The allele frequency was analyzed by Chi-square test.

In the group of patients, the frequency of G/G homozygotes was lower, and the frequency of G/A genotype was higher than the corresponding control group (p <0.05).

The results obtained from our study demonstrate an association between rs1064039 polymorphism in CST3 gene and late-onset AD in an Iranian population. Given the minimal significance level of the G/A genotype, this polymorphism seems to have minor effects on the progression of Alzheimer's disease or possibly interfere with other risk factors.
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Previous studies have shown the positive effect of aerobic exercise and curcumin on various variables in diabetes. Combination of these interventions may have an additive effect on these variables. The present study investigates the independent and combined effect of aerobic exercise and curcumin supplementation on cardiac SIRT1 gene expression and plasma resistin concentration in diabetic rats.

Forty male rats were equally divided into healthy control, diabetic control, diabetic exercise, diabetic curcumin, and diabetic curcumin+exercise. Aerobic exercise (five sessions/week, each session 30 minutes at a speed of 22 meters/minute, slope: five percent) and supplementation (30 mg/kg body weight, three days/week) were performed for eight weeks. Rats were sacrificed 48 hours after receiving the last intervention.

Diabetes decreased the expression of cardiac SIRT1 gene (p=0.001) and increased plasma resistin concentration (p =0.001). Exercise increased the expression of SIRT1 gene (p= 0.044) and decreased the resistance of resistin (p = 0.001) in diabetic rats. Curcumin also increased SIRT1 gene expression (p=0.048) and decreased resistin concentration (p=0.001) in diabetic rats. Compared to exercise or supplementation, combination of exercise and supplementation had more significant effect on increasing the expression of SIRT1 gene and decreasing the plasma concentration of resistin (p < 0.05).

In diabetic rats, aerobic exercise combined with curcumin has more pronounced beneficial effects on myocardial SIRT1 gene expression and plasma resistin concentrations from each alone.
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Although the analgesic effect of vitamin C was reported in several studies, its supra-spinal analgesia and the involved mechanisms have not been investigated yet. In this study, central effect of vitamin C in formalin-induced pain was investigated. Naloxone (an opioid receptor antagonist) and AM251 (a CB1 receptor antagonist) were used to clarify the possible mechanism of this vitamin.

In ketamine-xylazine anesthetized rats, one stainless-steel guide cannula was implanted into the fourth ventricle of the brain. The formalin test was induced by intra-plantar injection of formalin (50 mL, 2.5%), and the time spent licking and biting of the injected paw was recorded for 1 h.

A marked biphasic (first phase: 0–5 min and second phase: 15–50 min) pain response was induced after formalin injection. Intra-fourth ventricle injection of vitamin C significantly (p < 0.05) decreased both phases of pain. Naloxone and AM251 had no effect on the pain intensity. However, the analgesic effect of vitamin C was inhibited by pretreatments  with  naloxone and AM251. All the above-mentioned treatments did not alter locomotor activity of the animals.

These results showed that vitamin C suppresses formalin-induced neurogenic and inflammatory pains in rats through central modulatory mechanisms. Opioid and cannabinoid receptors play a role in the analgesic effects of vitamin C.

Extraction of Toxoplasma gondii genomic DNA from rat brain is challenging due to low level of contamination and high fat content. Quantitative real-time polymerase chain reaction (RT-qPCR) is associated with false negative results despite detecting small amounts of the gene. By changing method of DNA extraction, we could decrease number of false negative results.

Brains of eleven male Wistar rats infected with Tehran strain of Toxoplasma parasite (with 8 weeks of parasite infection) and three uninfected rats were isolated. The whole brain was used to purify DNA instead of 20 mg brain in the conventional method. Amount of protein kinase was doubled and the incubation period increased to 6 times. Then DNA of the samples was measured by RT-qPCR.

Only three of the eleven infected rats were infection positive by the conventional method, while nine mice were positive by the optimizing method.
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Orexin or Hypocretin is a neuropeptide, produced in the lateral hypothalamic neurons. The neurons send their projections throughout the brain and apply region-specific modulatory functions. Two discovered primary functions of orexin are the involvement of orexin in food intake and sleep regulation. The regulation of neurobiological mechanisms involved in the stress response is one of the most important orexin functions. Orexin terminals and receptors are distributed in many memory and stress-related areas such as the hippocampus. Stress, as a homeostatic challenge, leads to the malfunction of learning and memory processes. Orexin affects the behavioral and physiologic signs of stress by enhancing the activity of the paraventricular nucleus and secretion of corticotropin-releasing hormone, which in turn reinforces the function of orexin neurons, as a reciprocal circuitry. This mutual activation establishes a kind of positive feedback mechanism and a form of stress memory in the circuitry. Further studies are necessary for a better understanding of central and peripheral orexin functions and these results may help treat diseases especially anxiety disorders. We will review the recent findings regarding orexin and its role in stress response.