fariba khodagholi

Oxytocin (OXT) has attracted attention as an effective treatment for anxiety and depression. It also can prevent 3-NP-induced anxiety and depression. However, the effects of OXT can be context-dependent. The objective of this investigation was to explore how prenatal stress (PS) context modulates the effectiveness of OXT in mitigating anxiety-and depression-like behaviors induced by 3-NP, as well as alterations in antioxidant levels. 

The dams underwent PS or PS+3NP treatments, and the effects of OXT on the anxiety-like behavior, and depression-like behavior in these treatment groups were evaluated via elevated plus maze and forced swim test respectively. The reduced glutathione (GSH) level was also measured in the striatum, hippocampus, prefrontal cortex, and amygdala. 

We found that PS per se and 3-NP in the context of PS increased anxiety and depression. These groups also had lower GSH levels in the brain regions examined. OXT pretreatment markedly increased the behavioral changes in the PS group and ameliorated the antioxidant changes. However, OXT pretreatment could not improve 3-NP-induced behavioral and GSH level changes in the context of PS. 

These findings indicate that OXT improves PS-induced anxiety and depression and the antioxidant level changes, but we found that PS per se thwarts the protective effects of OXT in the 3-NP-induced anxiety and depression

Methamphetamine (Meth) is a highly addictive psychostimulant and induces neuroinflammatory responses. Melatonin is a neurohormone that has protective effects and reduces inflammation in the central nervous system. Our study focused on the melatonin effect on memory impairment, NLRP3/IL-1β axis, and gasdermin D and caspase-1 expression in the hippocampus of a rat model of Meth use.

Meth and melatonin were administered to the rats for 21 consecutive days. The memory was evaluated using alternation behavior in Y-maze. NLRP3 and IL-1β were assessed by western blotting and ELISA, respectively.  Gasdermin D and caspase-1 expression levels were evaluated using qRT-PCR.

The NLRP3 and IL-1β were elevated in the hippocampus following Meth injection. Moreover, Meth increased gasdermin D and caspase-1 expression levels. After 21 days of Meth use, memory impairment was seen in the Y-maze test. Melatonin significantly improved memory and decreased the expression of NLRP3, IL-1β, gasdermin D, and caspase-1 in the hippocampus.

Our study revealed that inflammasome formation and pyroptosis pathway are involved in Meth-induced neurotoxicity. Melatonin may be a potential treatment against neurotoxicity and cognitive disorders caused by Meth.

A 40-Hz white light emitting diode (WLED) has emerged as an alternative nonpharmacological and noninvasive approach to Alzheimer disease (AD). Here, we investigated the therapeutic effects of 40-Hz WLED on psychiatric symptoms (PS) and the contribution of mitochondrial factors in the early stages of sporadic AD (sAD) in rats.

In male Wistar rats, the AD model was induced via intracerebroventricular (ICV) injection of streptozotocin (STZ). After recovering (7 days) from stereotaxic surgery, 40-Hz WLED exposure was performed for 7 consecutive days lasting 15 min/d. Behavioral (elevated plus maze (EPM), force swim test, and social interaction test), enzymatic, and molecular assays were conducted 24 hours after the last 40-Hz WLED exposure.

Behavioral tasks revealed that 40-Hz WLED exposure in STZ-induced toxicity rats lowered anxiety and depression and increased social interaction. Furthermore, the 40-Hz WLED therapy in STZ-induced toxicity rats increased catalase (CAT) activity in the amygdala, decreased the activity of monoamine oxidases A and B in the whole brain, and increased mitochondrial DNA in the hippocampus.

The current study supports that 40-Hz WLED therapy improved PS and biomarkers in the early stages of sAD. Also, a potential relationship between PS and alterations in mitochondrial markers in certain brain regions seems to exist.

Peroxisomes are essential organelles in lipid metabolism. They contain enzymes for β-oxidation of very long-chain fatty acids (VLCFA) that cannot be broken down in mitochondria. Reduced expression in hepatic acyl-CoA oxidase 1 (ACOX1), a peroxisome β-oxidation enzyme, followed by modification of the brain fatty acid profile has been observed in aged rodents. These studies have suggested a potential role for peroxisome β-oxidation in brain aging. This study was designed to examine the effect of hepatic ACOX1 inhibition on brain fatty acid composition and neuronal cell activities of young rats (200-250 g). 

A specific ACOX1 inhibitor, 10, 12- tricosadiynoic acid (TDYA), 100 μg/kg (in olive oil) was administered by daily gavage for 25 days in male Wistar rats. The brain fatty acid composition and electrophysiological properties of dentate gyrus granule cells were determined using gas chromatography and whole-cell patch-clamp, respectively. 

A significant increase in C20, C22, C18:1, C20:1, and a decrease of C18, C24, C20:3n6, and C22:6n3 were found in 10, 12- tricosadiynoic acid (TDYA) treated rats compared to the control group. The results showed that ACOX1 inhibition changes fatty acid composition similar to old rats. ACOX1 inhibition caused hyperpolarization of resting membrane potential, and also reduction of input resistance, action potential duration, and spike firing. Moreover, ACOX1 inhibition increased rheobase current and afterhyperpolarization amplitude in granule cells. 

The results indicated that systemic inhibition of ACOX1 causes hypo-excitability of neuronal cells. These results provide new evidence on the involvement of peroxisome function and hepatic ACOX1 activity in brain fatty acid profile and the electrophysiological properties of dentate gyrus cells.

Negative early-life experiences (e.g. having an aggressive father) can leave long-lastingimpacts on the behavior. However, it is not clear if they influence learning and memory. 

In this study, we investigated the influences that the presence of an aggressive father had on the level of passive avoidance learning and spatial memory. We also studied the changes in the dopamine receptor D2 (DRD2) and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) gene expression in the hippocampus. Then, we evaluated if a DRD2 antagonist (sulpiride, 0.125, 0.25, or 0.5 μg/rat) could modulate these changes. 

We found that the subjects exposed to early-life stress made by aggressive fathers had impaired passive avoidance learning and spatial memory compared to subjects with normal fathers. Treatment with sulpiride improved passive avoidance learning and spatial memory in rats with aggressive fathers. The rats with aggressive fathers also had higher expression of the DRD2 gene in their hippocampus than those with normal fathers, while the PGC-1α gene expression was not different among groups. Treatment with sulpiride (0.125, 0.25, or 0.5 μg/rat) reduced the DRD2 gene expression in those with aggressive fathers to the normal level compared to those with normal fathers. 

These data suggest that having and living in a shared place with an aggressive father, even without any physical contact, can detrimentally affect passive avoidance learning and spatial memory which is accompanied by the increased expression of the DRD2 gene. Also, sulpiride as a dopaminergic antagonist could reverse this process.

Carbon-based nanomaterials (CBNs) are the key elements in nanotechnology. The main challenge presented by CBNs is their relationship with the toxicity exposed in the biological systems, because of the incomplete information on their toxicity. This study is aimed to compare the cytotoxicity of graphite nanoparticles (GRNPs), graphene nanoparticles (GNPs), and multi-walled carbon nanotubes (MWCNTs) in A549 cells.
The physicochemical properties of nanomaterials were determined by instrumental techniques. CBNs were dispersed by the nongenotoxic standard procedure. After the cells were cultured, they were exposed to different concentrations of CBNs. Cellular viability was determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. Moreover, toxicological indicators were obtained using linear probit regression.
The degree of cytotoxicity of CBNs in A549 cells was related to the time and, particularly, dose. At the concentrations of lower than 300 μg/mL, GNPs had stronger toxicity than MWCNTs, but the cytotoxic effects were reversed with the increase of the concentrations. The no-observed-adverse-effect concentration (NOAEC) of GRNPs, GNPs, and MWCNTs was 1.76, 0.06, and 0.65 μg/mL, respectively.
The results indicated that CBNs were toxic and GNPs had stronger toxicity than the others. The experimental results can be useful in increasing the knowledge about the toxicity and health risk management of CBNs.

The aim of the present study was determination of the effect of eight weeks of Endurance Training (ET) on amount of KIF5B protein in Soleus and Extensor Digital Longus muscle tissue in aged male Wistar race rats.

12 Aged male rats with an average age of eighteen to twenty-four months and an average weight of 407.83 ± 21.29 grams and 6 young rats with an average age of eight to ten weeks and an average weight of 180.67 ± 10.36 grams were randomly divided into 3 groups of six series (aged endurance training, aged sham exercise and young sham exercise). The aged endurance training group ran continuously on a treadmill for 15 to 60 minutes with intensity of 7.5-15 meter/ Min, 5 days a week for eight weeks. To measure the amount of KIF5B protein, ELISA method and to test the hypotheses, one-way analysis of variance and Tukey's post hoc test were used.

Following aging, the amount of KIF5B protein decreased significantly in soleus and EDL muscle. Eight weeks of ET caused a significant increase in the amount of KIF5B protein in the soleus and EDL compared to the aged sham exercise. The ratio of the weight of Soleus and EDL to body weight in the ET group had a significant increase compared to the aged sham exercise.

Following a regular training period of ET, the amount of KIF5B protein in the soleus and EDL muscles as well as the peak running speed of aged male rats increased and reduced sarcopenia by increasing the relative weight of soleus and EDL muscles in them.

The reduction of effective motor proteins in axoplasmic transport is proposed as a possible reason for the occurrence of sarcopenia. The aim of the present study was determination of the effect of eight weeks of resistance training on amount of KIF5B protein in soleus and extensor digital longus (EDL) muscle tissue in aged male rats.

18 Aged and young male rats were randomly divided into 3 groups: aged resistance training, aged sham exercise and young sham exercise. The aged resistance training group climbed a one-meter ladder for eight weeks, 4 days a week, with one set and 8 repetitions, with a 2-minute rest interval between repetitions. To measure the amount of KIF5B protein, ELISA method was used, to measure the relative weight of muscles, a weighing scale was used, and to test the hypotheses, one-way analysis of variance and Tukey's post hoc test were used at the level of p≤0.05.

Following aging, the amount of KIF5B protein decreased significantly in soleus muscle and EDL compare to Young Sham group. Eight weeks of resistance training caused a significant increase in the amount of KIF5B protein in the soleus and EDL compared to the aged sham exercise. The Relative weight of both muscles in the resistance training group had a significant increase compared to the aged sham exercise.

Eight weeks of resistance training increases the amount of KIF5B protein in soleus and EDL muscles and their hypertrophy in aged male rats.

Prevalence of obesity and its related disease is considered as a major health complication worldwide. Changing the phenotype of white adipose tissue to brown following exercise is currently being studied as one of the strategies to prevent obesity. The aim of this study was to investigate the effect of eight weeks of continuous and high intensity interval training (HIIT) on UCP1 of visceral and subcutaneous white adipose tissue in obese rats. Eighteen obese rats after eight weeks of high fat diet randomly divided into control, continuous training (CT) and HIIT groups. HIIT protocol included high intensity intervals (80-110 % vVO2max) and low intensity intervals (50 % vVO2max) and CT protocol included running with (65-75 % vVO2max) intensity. 48 hours after the last training session, rats were sacrificed, visceral and subcutaneous white adipose tissue were removed and UCP1 level was assessed through western blotting method. The results showed that eight weeks of CT and HIIT increase UCP1 in visceral and subcutaneous WAT (p<0.05), and this increase were higher in HIIT group regardless of visceral or subcutaneous adipose tissue (P<0.005). It seems that HIIT induce higher increase in UCP1 protein in visceral and subcutaneous white adipose tissue, so obese individuals can use this type of training to benefit obesity prevention affects and improvement of adipose tissue function.

The aim of this study was to determine the effect of four weeks of incremental endurance training on Sarcolipin (SLN), FNDC5, and PGC1α protein levels in the soleus (SOL) and extensor digitorum longus (EDL) muscle of adult male Wistar rats.

In this experimental study, 14 adult male Wistar rats were divided into two groups of control (n=7) and training (n=7). The training group performed endurance exercises for 4 weeks and 5 sessions per week, which included running at the intensity of 75 to 80% of the vo2max. In rat surgery, SOL and EDL muscles were extracted, followed by changes in SLN proteins, and intramuscular FNDC5 and PGC1α were measured by Western blotting technic. Data were statistically analyzed by independent t-test (P≤0.05).

The results of statistical analysis showed that four weeks of incremental endurance training caused significant changes in the amounts of SLN (P = 0.035), FNDC5 (P = 0.02), and PGC1α (P = 0.012) proteins. In the soleus muscle, compared to the control group. Also, in EDL muscle, significant changes were observed in the amounts of SLN (P = 0.01) and FNDC5 (P = 0.043) proteins in comparison with the control group, but in the changes of PGC1α protein in EDL muscle compared to the control group, no significant difference was observed (P = 0.17).

According to the parameters of the study, it seems that endurance exercise can increase the amount of proteins related to thermogenesis and metabolism.

Mitochondria and peroxisomes are tightly connected organelles that cooperate in lipid oxidation and maintenance of redox homeostasis. However, the peroxisome’s role in the modulation of the mitochondrial regulatory factors has remained unanswered. SIRT1- PGC-1α interaction as a pivotal pathway in energy expenditure leads to mitochondrial biogenesis. Histone deacetylase (HDAC)6 and HDAC10 also regulate mitochondrial dynamics. Mitochondrial dysfunction is a cause and/or consequence of aging and neurodegenerative disorders.

In this study, to disturb importing proteins into the peroxisomes, PEX5 was down-regulated in the dorsal hippocampus by lentivirus-mediated shRNA. The impact of PEX5 reduction on peroxisomes was explored by assessment of catalase activity, a regular peroxisome matrix enzyme, and PMP70 and PEX14 expression. Then, mitochondrial biogenesis factors, PGC-1α, and mitochondrial transcription factor A (TFAM) were measured by quantitative polymerase chain reaction and mitochondrial-related HDACs, SIRT1, SIRT3, HDAC6 and HDAC10, by western blotting. Besides, spatial learning and memory were assessed using the Morris water maze task.

Our results revealed a significant reduction of HDAC6 and SIRT1, alongside with decrease in mitochondrial biogenesis factors PGC-1α and TFAM, and no alteration in HDAC10 and SIRT3. Despite all observed changes, memory performance displayed no detectable alteration in the experimental groups. These data suggest the role of peroxisomes in modulating mitochondrial dynamics via regulation of HDAC6 and SIRT1 expression.

Peroxisome dysfunctions may occur upstream to mitochondrial failure and can be considered as a potential therapeutic target for aging and age-related disorders.

Little attention has been paid to the effects of combined exposure to noise and vibration. Exposure to noise and vibration can effect stress hormones and may lead to high blood pressure and cardiovascular disorders. This study aims to investigate the effects of noise and vibration on urinary Metanephrine and Normetanephrine among men.

In this experimental study, 30 male students were deemed eligible for entry. Background variables such as temperature, light intensity, sound pressure level and vibration acceleration (before and after exposure) were measured throughout each experiment. Participants were randomly exposed to two noise levels and two vibration accelerations for 30 minutes in a combined and independent exposure condition. Urine samples were taken an hour before and an hour after exposure. Metanephrine and Normetanephrine levels were measured using the ELISA method and a specialized Metanephrine/Normetanephrine urinary measurement kit. A repeated measures regression with a Generalized Estimating Equations (GEE) approach was applied for data analysis.

The exposure to noise (at 85 and 91 dB(A)) and independent exposure to whole body vibration at 1.85 m/s2 caused an increase in Normetanephrine and a decrease in Metanephrine concentration although these changes were not statistically meaningful (P>0.05). Combined exposure to noise and vibration caused an increase in Metanephrine and Normetanephrine concentration. These changes were also not statistically significant (P>0.05).

Study subjects’ stress hormone concentrations changed when exposed to noise but did not follow a particular trend. Short term exposure (30 minutes) did not have a distinguish effect on urinary Metanephrine and Normetanephrine concentrations. Therefore, urinary Metanephrine and Normetanephrine concentrations cannot be considered appropriate indicators for noise and whole body vibration exposure.

Prostate cancer is one of the most common cancers and the second major cause of mortality in men. Different researches have shown that the overexpression of a gene called twist1 leads to initiation of metastasis process in this cancer. TWIST1 protein triggers this process through stimulating the transition pathway of cells from epithelial to mesenchymal tissue.

In this study, four oligonucleotides of antisense RNA have been designed for twist1 gene, and its anti-metastatic effect was examined in two cell lines PC3 and LNCaP. The antisense oligonucleotides (ASOs) were designed as single strands with a length of 20 nucleotides and chosen from ASOs suggested by Soligo program. The ASOs were synthesized in phosphorothioated form. MTT assay was used for evaluating the ASOs cytotoxicity effect on PC3 and LNCaP cell lines. The cell lines were transfected with 500 nmol of antisense oligonucleotides using cationic polymer turbofect and incubated for 48 hours, and then, their invasive ability were measured by CytoSelect™ Cell Invasion Assay Kit.

The anti-invasive effect of ASOs in LNCaP and PC3 had a significant difference. This effect was more significant in LNCaP cell line as compared to PC3. The most anti- invasive effect was observed in LNCaP cell line (50%).

According to the results, Antisense oligonucleotides were effective in decreasing the invasion ability of two cell lines PC3 and LNCaP and therfore can be considered as a good candidate for preventing the prostate cancer metastasis.

Sleep deprivation (SD) in the long term can cause multi-organ dysfunction as well as neurocognitive disorders. Daytime sleep or napping is a biological compensate due to insomnia or sleep deprivation. Metabolic responses to this biological rhythm may being as a biological indicator or biomarker to compare the effect of them. Glucose transporter type 1 (Glut1) is one of the metabolic biomarkers that is affected by several conditions such as stress, seizure, malignancy, and neurocognitive disorders. We studied the effect of SD, circadian reversed (R) and napping models on the Glut-1 expression level in the right and left amygdala.

Sixty-four Wistar rats were divided into eight groups as follow: Intact group that rats were placed in a cage without any intervention. In the sham group, rats were on the stable pedal of the SD apparatus (turn off). Experimental groups include total SD48, total SD48- (plus short nap), total SD48+ (plus long nap), R48, R48- (plus short nap), and R48+ (plus long nap). The Glut-1 expression level in the right and left amygdala were measured by western blotting.

Our findings demonstrated the significant effect of both SD for 48 hours and reversed circadian on the expression of Glut-1 from sham and intact groups. The long nap plus them could decrease the elevation of Glut-1 in the left amygdala. However, the short nap could not reduce this elevation of Glut-1.

Left amygdala is vulnerable to the fluctuation of hypothalamicpituitary-adrenal axis and stress. In other words, sleep disorders are affecting by Glut-1 as a metabolic biomarker in left amygdala alone.

Early life stress (ELS) models such as maternal deprivation (MD) are used to investigate behavioral changes in rodents under stressful situations. MD is a situation in which rat pups are separated from the dam; MD has different paradigms. The purpose of this research is to evaluate the effects of maternal deprivation on anxiety, depression, and empathy in adult Wistar rats.

MD was applied to pups as per specifically designed protocol to compare rats of the control group with maternal deprivation rats and also the group, which faced novel objects. Each group consisted of eight rats. In this study, separation started from postnatal day (PND) 14 for various periods up to PND 60. EPM test was undertaken to measure anxiety; moreover, FST was used to indicate levels of depression. Also, changes in the empathy ratio were also demonstrated. One-way analysis of variance (ANOVA), Tukey’s post hoc analysis, and t-test were applied to analyze the results.

MD-treated rats showed a significant decrease in anxiety and empathy indexes compared with those in the control group (P<0.05). However, MD significantly increased depression in both male and female rats (P<0.05). Finally, exposure to novel objects decreased depression but did not have any effect on anxiety and empathy levels in MD rats (P<0.05).

ELS may lead to various states of mood and behavior in adulthood. According to the findings of this study, depression increases due to MD, though both anxiety and empathy decrease in both male and female Wistar rats. Moreover, exposure to novel objects decreases depression, while anxiety and empathy do not change significantly with exposure to novel objects.

While traumatic brain injury (TBI) is a predisposing factor for development of post-traumatic epilepsy (PTE), the occurrence of seizures following brain trauma can infuriate adverse consequences of brain injury. However, the effect of seizures in epileptogenesis after mild TBI cannot yet be accurately confirmed. This study was designed to investigate the histopathological and molecular modifications induced by seizures on traumatized brain. Using a new method, head was traumatized and seizures were evoked by sub-convulsive dose of pentylenetetrazole (PTZ) fifteen days after induction of focal mild TBI. Convulsion assessments were performed one hour after PTZ injection and was followed by histopathological and molecular evaluations. A significantly higher score and longer duration of seizure attacks as well as higher number of epileptiform discharges were observed in the TBI+PTZ group compared to sham and TBI groups. An elevated number of apoptotic cells was observed in the TBI+PTZ group compared to sham and TBI rats. Molecular investigations revealed higher levels of Bax/Bcl2 ratio, Caspase 3, and NF-κB in the TBI+PTZ group compared to the other animal groups. The value of Nrf2 did not change after mild TBI compared to sham and PTZ control groups. Occurrence of seizures after TBI, however, significantly decreased the level of Nrf2. Our data indicated that seizure occurrence following mild TBI aggravates cell injury and death via activation of neuroinflammatory processes and may increase the risk of PTE. Additionally, our results suggest a potential protective role of Nrf2 after chemically evoked PTE.

Alzheimer's disease (AD) is a progressive brain disorder that is associated with dementia. The entorhinal cortex (EC) is one of the first brain regions affected in AD. High level of beta-amyloid (Aβ) is seen in various brain regions, including the EC. Previous studies have shown that Aβ causes calcium dyshomeostasis. In this study, molecular changes in the CA1 region following microinjection of Aβinto the EC and the potential protective role of calcium channel blockers was investigated.

Aβ (1 µg/2 μl) was injected into the right EC of male Wistar rats under stereotaxic surgery, and then a guide cannula was planted in the right ventricle. Isradipine and nimodipine were intraventricularly injected at 30 μg daily for 6 days. On the seventh day, the expression of Calpain 2, Caspase 12 and 3 in hippocampal CA1 was measured by western blot technique. Pro-apoptotic changes were also assessed by Tunnel test.

Results indicated that Aβ injection into the EC increased the expression of Calpain 2, Caspase 12 and 3 in the CA1 region. Apoptotic cells were also increased in the CA1 region following amyloidopathy in the EC. Following the treatment of the rats with isradipine and nimodipine, the expression of Calpain 2, Caspase 12 and 3 decreased, and the number of apoptotic cells was returned to the control level.

EC amyloidopathy may change the molecular profile associated with apoptosis in neighbor regions such as CA1 and treatment with calcium channel blockers can prevent the changes.

Entorhinal cortex (EC) is one of the first Entorhinal cortex (EC) is one of the first cerebral regions affected in Alzheimer’sdisease (AD). The pathology propagates to neighboring cerebral regions through a prion-likemechanism. In AD, intracellular calcium dyshomeostasis is associated with endoplasmicreticulum (ER) stress. This study was designed to examine hippocampal ER stress followingEC amyloidopathy. Aβ1-42 was bilaterally microinjected into the EC under stereotaxic surgery.Rats were daily treated with 30 μg of isradipine, nimodipine, or placebo over one week.Passive avoidance and novel object recognition (NOR) tasks were performed using shuttle boxand NOR test, respectively. GRP78/BiP and CHOP levels were measured in the hippocampaldentate gyrus (DG) by western blot technique. The glutathione (GSH) level and PDI activitywere also assessed in the hippocampus by colorimetric spectrophotometer. Aβ treated groupdeveloped passive avoidance and novel recognition memory deficit compared to the controlgroup. However, treatment with calcium channel blockers reversed the impairment. BiP andCHOP level increased in the hippocampus following amyloidopathy in the EC. PDI activityand GSH level in the hippocampus decreased in the Aβ treated group, but calcium channelblockers restored them toward the control level. In conclusion, memory impairment due to ECamyloidopathy is associated with ER stress related bio-molecular changes in the hippocampus,and treatment with L-type calcium channel blockers may prevent the changes and ultimatelyimprove cognitive performance.cerebral regions affected in AD. Intracellular calcium buffering capacity is disrupted in the dentate gyrus (DG) following EC amyloidopathy. This study was designed to examine hippocampal endoplasmic reticulum (ER) stress following EC amyloidopathy. Aβ1-42 was bilaterally microinjected into the EC under stereotaxic surgery. Rats were daily treated with 30 μg of isradipine, nimodipine or placebo over one week. Passive avoidance and novel object recognition (NOR) tests were performed. GRP78/BiP and CHOP levels were measured in the hippocampal DG. The glutathione (GSH) level and PDI activity were also assessed in the hippocampus. Aβ treated group developed passive avoidance and novel recognition memory deficit compared to the control group. However, treatment with calcium channel blockers reversed the impairment. BiP and CHOP level increased in the hippocampus following amyloidopathy in the EC. PDI activity and GDH level in the hippocampus were decreased in the Aβ treated group, but calcium channel blockers restored them toward the control level. In conclusion, memory impairment due to EC amyloidopathy is associated with ER stress related bio-molecular changes in the hippocampus, and treatment with L-type calcium channel blockers may prevent the changes and ultimately improve cognitive performance.

Preconditioning (PC) as a protective strategy against noxious insults can decline cell death and apoptosis. It has been approved that mitochondria play a key role in PC mechanism. The critical role of complex I (CI) in oxidative phosphorylation machinery and intracellular ROS production, particularly in the brain, accentuates its possible role in PC-induced neuroprotection. Here, differentiated PC12 cells were preconditioned with ultra-low dose LPS (ULD, 3 μg/mL) prior to exposure to high concentration of LPS (HD, 750 μg/mL). Our results showed that HD LPS treatment reduces cell viability and CI activity, and intensifies expression of cleaved caspase 3 compared to the control group. Intriguingly, PC induction resulted in enhancement of cell2viability and CI activity and reduction of caspase3 cleavage compared to HD LPS group. In order to explore the role of CI in PC, we combined the ULD LPS with rotenone, a CI inhibitor. Following rotenone administration, cell viability significantly reduced while caspase3 cleavage increased compared to PC induction group. Taken together, cell survival and reduction of apoptosis followed by PC can be at least partially attributed to the preservation of mitochondrial CI function.

Peroxisomes are single membrane cell organelles with a diversity of metabolic functions. Here we studied the peroxisomal dysfunction and oxidative stress after 3-nitropropionic acid (3-NP) induced neurotoxicity and the possible protective effects of oxytocin. Adult male and female rats were subjected to Oxt and/or 3-NP treatment. The antioxidant enzymes, Superoxide dismutase (SOD) and Catalase (CAT) activities as well as expression level of Peroxin 14 (Pex14), a marker for peroxisomal number and Peroxisomal membrane protein of 70 kDa (PMP70), a metabolic transporter in peroxisome in different brain regions of both sexes were studied. The results indicated that 3-NP significantly decreased the expression level of Pex14 and PMP70 in various studied areas in male and female rats. In addition, 3-NP reduced the SOD and CAT activity in different brain regions in both sexes. OXT treatment increased the expression level of peroxisomal proteins Pex14 and PMP70 which are representative of peroxisome performance improvement. Besides, it ameliorated the antioxidant system capability through increasing the activity of the SOD and CAT in all studied brain regions including Striatum, Hippocampus, Prefrontal Cortex and Amygdala with no differences in male and female rats. This study demonstrated that toxin 3-NP, could ultimately cause peroxisomal malfunction and so determines the contribution of peroxisomal dysfunction in the etiology of HD pathology. OXT significantly increased peroxisomal function and antioxidant system defense capability, therefore illustrates that OXT might be an alternate treatment approach for the neurodegenerative diseases like HD.

The poor performance of capillary system and reduce in VEGF amount can be mentioned as one of the physiological complications that is caused by aging. Sprint training by more using fibers can be effective in improving performance of older people .The aim of this study was to investigate the effect of eight-week sprint interval training on VEGF amount of soleus muscle tissue and EDL in old Wistar male rats.

A total of twenty aged wistar rats with average weight of 489±43.72 (gr) were prepared and after one week familiarization with the laboratory conditions, were randomly divided into two groups: training (n=10) and control (n=10). SIT Training was included incremental and intermittent running on treadmill that performed three-four times in the week for eight weeks. Then were isolated the soleus and Extensor Digitorum Longus (EDL) muscles. Finally, we used western blot method to measure protein changes in the muscle tissue and t-test evaluating the information.

Difference between VEGF amount in control group and training group in both fast-twitch (p≤0.05) and slow-twitch muscles (p≤0.05) was significant.

The amount of capillarization in type II fibers have shown more decreases in comparison with type I fibers because of aging, therefor according to the result of this study it can be concluded that sprint interval training may be a proper stimulus to angiogenesis and leads to improvement of its metabolic properties.

The purpose of this study was to determine the effect of single bout of continuous exercise and high intensity interval exercise on Hypoxia Inducible Factor-1alph (HIF-1α) and Tumor Necrosis Factor-alph (TNFα) levels in adipose tissue of obese male Wistar rats. Subject was 30 obese male Wistar rat that intake high fat diet for 8 weeks. Subject done an exhaustive test to assess VO2max for determine the exercise intensity then divided into three groups: Control, continuous and High Intensity Interval Exercise (HIIE). The HIIE protocol was five 2min sets of high intensity exercise (100% vVO2max) which separated whit four sets of low intensity exercise (30% vVO2max). Continues group intensity was 65% vVO2max and the running time measured by interval sets distance in HIE group. Western blotting analysis use for determine protein levels in visceral and subcutaneous adipose tissue and data analysis was performed with SPSS software. Based on data HIF-1α level reduce significantly 33.5% and 45% in continues and HIIE group respectively (P

Sprint training by more using fast twitch fibers and likely changes in muscle phenotype, can be effective in improving performance of older people. The purpose of this study was evaluating effect of eight weeks Sprint Interval Training (SIT) on myogenin rate in wistar aged rats fast-twitch and slow-twitch muscles.

A total of twenty aged wistar rats with average weight of 489±72/43 (gr) were prepared and after one week familiarization with the laboratory conditions, were randomly divided into two groups: training (n=10) and control (n=10). SIT Training was included incremental and intermittent running on treadmill that performed three-four times in the week for eight weeks. Then were isolated the soleus and Extensor Digitorum Longus (EDL) muscles. Finally, we used western blot method to measure protein changes in the muscle tissue and t-test evaluating the information.

The results showed that although myogenin increased in both types of muscles but increasing was higher in fast muscle. So that in the EDL muscle, it significantly increased more than two times (99%), whereas increased only 1/3 times (29%) in the soleus muscle and changes were not significant) P

So fast-twitch muscle is targeted by this study protocol likely. Accordingly, myogenin was higher in the EDL muscle. On the other hand, this increasing probably due to the phenotype changes of muscle fibers or as a result of muscle hypertrophy.

“VARD” formula consisting of Rosa damascena Mill. (Rosaceae) petal, and rhizomes of Glycyrrhiza glabra L. (Papilionaceae) and Nardostachys jatamansi DC. (Valerianaceae), has been proposed for gastric ulcer in Iranian traditional medicine. We investigated the antiulcer activity of each plant separately and in combination. The biochemical and molecular function of extracts was also evaluated. Each plant hydroalcoholic extract was standardized via determination of total phenolic and flavonoid, also phenolic compounds determination and specially glycyrrhizic acid in G. glabra by using HPLC. Rats received orally extracts of the plants (20, 40, and 80 mg/kg) and “VARD” (45 mg/kg) 1 h before ethanol administration. Two hours after receiving ethanol, animals were sacrificed; the stomach was removed for macroscopic and microscopic assessment. Also heme-oxygenase-1, glutathione, and catalase were measured in the gastric tissue of the rats pretreated by “VARD” and dose of 20 mg/kg of extracts. Among three extracts, R. damascena and G. glabra contained more total phenolic and flavonoid content respectively. Gallic acid was prominent compound in R. damascena. The extracts of R. damascena, G. glabra, and N. jatamansi significantly decreased ulcer index. ED50 values were 8.2, 31.86 and 25.08 mg/kg respectively. “VARD” significantly decreased ulcer index compared to 20 mg/kg of G. glabra (p

Necroptosis, as a novel concept, has been recently introduced in scientific literature. Much of our knowledge about necroptosis comes from ligation of tumor necrosis factor-α to its receptor, TNF receptor 1. Receptor-interacting protein kinase 1, receptor-interacting protein kinase 3 and its substrate, the pseudokinase mixed lineage kinase domain-like protein, have been comprehensively studied as influential components of this process. Emerging pioneering evidence suggests that many molecules, organelles and mechanisms are involved in necroptosis pathway. The aim of this review is presentation of molecular mechanisms of necroptosis in three phases including initiation, regulation and execution of necroptosis. Moreover, this review will summarize unprecedented insights into the contribution of various organelles and cell compartments such as mitochondria, endoplasmic reticulum, nucleus, lysosomes and Golgi apparatus in necroptosis pathway.