Resveratrol and 1,25-dihydroxyvitamin D decrease Lingo-1 levels, and improve behavior in harmaline-induced Essential tremor, suggesting potential therapeutic benefits.

Essential tremor (ET) is a neurological disease that impairs motor and cognitive functioning. A variant of the Lingo-1 genetic locus is associated with a heightened ET risk, and increased expression of cerebellar Lingo-1. Lingo-1 has been associated with neurodegenerative processes; however, neuroprotection from ET-associated degeneration can be conferred by the protein Sirt1. Sirt1 activity can be promoted by Resveratrol (Res) and 1,25-dihydroxyvitamin D3 (VitD3), and thus these factors may exert neuroprotective properties through a Sirt1 mechanism. As Res and VitD3 are linked to Sirt1, enhancing Sirt1 could counteract the negative effects of increased Lingo-1. Therefore, we hypothesized that a combination of Res-VitD3 in a harmaline injection model of ET would modulate Sirt1 and Lingo-1 levels. As expected, harmaline exposure (10 mg/kg/every other day; i.p.) impaired motor coordination, enhanced tremors, rearing, and cognitive dysfunction. When Res (5 mg/kg/day; i.p.) and VitD3 (0.1 mg/kg/day; i.p.) were given to adult rats (n = 8 per group) an hour before harmaline, tremor severity, rearing, and memory impairment were reduced. Individual treatment with Res and VitD3 decreased Lingo-1 gene expression levels in qPCR assays. Co-treatment with Res and VitD3 increased and decreased Sirt1 and Lingo-1 gene expression levels, respectively, and in some cases, beneficial effects on behavior were noted, which were not seen when Res or VitD3 were individually applied. Taken together, our study found that Res and VitD3 improved locomotor and cognitive deficits, modulated Sirt1 and Lingo-1. Therefore, we would recommend co-treatment of VitD3 and Res to leverage complementary effects for the management of ET symptoms.

The role of transcranial direct current stimulation in diminishing the risk of pneumonia in patients with dysphagia: A double-blinded randomized clinical trial.

Background: Dysphagia can be a life-threatening issue for post-stroke patients, with aspiration pneumonia (AP) being a common risk. However, there is hope through the potential combination of transcranial direct current stimulation (tDCS) and classical behavior therapy. Our study aims to investigate the effectiveness of this combination in diminishing the risk of AP in patients with dysphagia who suffered from stroke. Methods: In this randomized, parallel-group, blinded clinical trial, 48 patients were allocated into the sham group (speech therapy + 30 seconds of tDCS) and the real group (speech therapy + 20 minutes of tDCS). We used the Mann Assessment of Swallowing Ability (MASA) as an assessment tool. We assessed patients at baseline, one day after treatment, and at a one-month follow-up. Results: Groups showed no significant difference at baseline. After treatment, the real group showed a significant difference in the severity risk of AP (P = 0.02); the same was for the follow-up (P = 0.04). The number of patients showing severe risk of AP was higher in the sham group after treatment (n = 13, 54.20%) and at follow-up (n = 4, 18.20%) than the real group (n = 4, 16.70%; n = 1, 4.50%, respectively). None of the patients reported the history of AP at any stage of assessment. Conclusion: Although the results were more promising in the real group than the sham group in reducing the risk of AP, both techniques can prevent AP. Therefore, we recommend early dysphagia management to prevent AP regardless of the treatment protocol.

Gallic acid improves liver cirrhosis by reducing oxidative stress and fibrogenesis in the liver of rats induced by bile duct ligation.

Disturbance in the production and excretion of bile acid causes cholestatic liver disease. Liver cirrhosis is a disease that occurs if cholestasis continues. This study evaluated the protective effect of gallic acid (GA) on liver damage caused by biliary cirrhosis. Rats were randomly divided into 4 groups, each with 8 subjects: 1) control, 2) BDL, 3) BDL + GA 20, and 4) BDL + GA 30. The rats were anesthetized 28 days after the BDL, followed by collecting their blood and excising their liver. Their serum was used to measure liver enzymes, and the liver was used for biochemical analysis, gene expression, and histopathological analysis. Serum levels of liver enzymes, total bilirubin, liver Malondialdehyde level (MDA), expression of inflammatory cytokines and caspase-3, necrosis of hepatocytes, bile duct proliferation, lymphocytic infiltration, and liver fibrosis showed an increase in the BDL group compared to the control group (p < 0.05). In addition, BDL decreased the activity of liver antioxidant enzymes and glutathione (GSH) levels compared to the control group (p < 0.05). The groups receiving GA indicated a decrease in liver enzymes, total bilirubin, MDA, the expression of inflammatory cytokines and caspase-3, and a reduction in liver tissue damage compared to the BDL group (p < 0.05). The level of GSH in the BDL + GA 20 group showed a significant increase compared to the BDL group (p < 0.05). Moreover, it was found that GA, with its anti-fibrotic and anti-inflammatory properties, reduces liver damage caused by biliary cirrhosis.

Effect of l -Dopa in acute temozolomide-induced cognitive impairment in male mice: a possible antineuroinflammatory role.

Temozolomide is used commonly in the treatment of some types of cancers, but it may also result in cognitive impairments such as memory deficits. l -Dopa, a well known medicine for the central nervous system, has been shown to have positive effects on some cognitive disorders. Here we sought to investigate the effect of l -Dopa on temozolomide-induced cognitive impairments. BALB/c mice were subjected to 3-days temozolomide and 6-days concomitant l -Dopa/benserazide administration in six groups (control, l -Dopa 25 mg/kg, l -Dopa 75 mg/kg, temozolomide, temozolomide +  l -Dopa 25 mg/kg, and temozolomide +  l -Dopa 75 mg/kg). Open field test, object location recognition, novel object recognition test, and shuttle-box test were carried out to determine the locomotor, anxiety-like behavior, and memory function of subjects. TNF-α and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus was measured by real-time PCR. Mice treated with temozolomide showed recognition memory impairment, along with hippocampal TNF-α and BDNF mRNA expression level raise, and detection of histological insults in hematoxylin and eosin hippocampal slides. Mice that received temozolomide +  l -Dopa showed normal behavioral function and lower TNF-α and BDNF hippocampal mRNA expression levels, and histologically normal hippocampal CA1 region in comparison with mice in the temozolomide group. Our results provide evidence that l -Dopa prevents temozolomide-induced recognition memory deficit in mice at the acute phase probably via l -Dopa antineuroinflammatory effects.

Agmatine improves liver function, balance performance, and neuronal damage in a hepatic encephalopathy induced by bile duct ligation.

INTRODUCTION: In the current study, we investigate whether oral administration of agmatine (AGM) could effectively reduce motor and cognitive deficits induced by bile duct ligation (BDL) in an animal model of hepatic encephalopathy (HE) through neuroprotective mechanisms. METHODS: The Wistar rats were divided into four groups: sham, BDL, BDL+ 40 mg/kg AGM, and BDL+ 80 mg/kg AGM. The BDL rats were treated with AGM from 2 weeks after the surgery for 4 consecutive weeks. The open field, rotarod, and wire grip tests were used to assess motor function and muscle strength. The novel object recognition test (NOR) was performed to evaluate learning and memory. Finally, blood samples were collected for the analysis of the liver markers, the animals were sacrificed, and brain tissues were removed; the CA1 regions of the hippocampus and cerebellum were processed to identify apoptosis and neuronal damage rate using caspase-3 immunocytochemistry and Nissl staining. RESULTS: The serological assay results showed that BDL severely impaired the function of the liver. Based on histochemical findings, BDL increased the neuronal damage in CA1 and Purkinje cells, whereas apoptosis was significantly observed only in the cerebellum. AGM treatment prevented the increase of serum liver enzymes, balance deficits, and neuronal damage in the brain areas. Apoptosis partially decreased by AGM, and there were no differences in the performance of animals in different groups in the NOR. CONCLUSIONS: The study suggests AGM as a potential treatment candidate for HE because of its neuroprotective properties and/or its direct effects on liver function.

Naringenin mitigates reserpine-induced anxiety-like behavior, neurodegeneration, and oxidative stress in male rats.

Reserpine (Res) induces anxiety-like behaviors, orofacial dyskinesia, and neurodegeneration in animals, the pathophysiology of which has been related to oxidative stress. The purpose of this study was to investigate whether naringenin (NG) could prevent reserpine-induced anxiety-like behaviors, orofacial dyskinesia, and neurodegeneration in male rats. Twenty-eight male rats were distributed into different groups as follows: Control rats; vehicle rats, which received the vehicles (normal saline, orally; acetic acid, intraperitoneally); Res rats (1 mg/kg/day) every other day for 3 days; and Res + NG rats, which received NG (50 mg/kg, orally, pre-treatment for 7 days), followed by Res. Administration of Res significantly increased chewing frequency compared with the control group (P < 0.01) and NG reversed the effect of Res on this factor (P < 0.05). Res induced an anxiety-like behavior in rats in the plus maze, and pre-treatment with NG improved this behavior. In addition, Res significantly increased the level of oxidative stress markers and degenerated neurons in the striatum; NG was able to ameliorate these damages. The results of this study demonstrated that Res caused behavioral disorders and increased the levels of oxidative stress in male rats; the use of NG was effective in treating these disorders. Therefore, NG should be considered as a preventive agent for reserpine-induced brain damage in male rats.

Impact of ketamine administration on chronic unpredictable stress-induced rat model of depression during extremely low-frequency electromagnetic field exposure: Behavioral, histological and molecular study.

OBJECTIVES: In the study, we examined the effects of ketamine and extremely low-frequency electromagnetic fields (ELF-EMF) on depression-like behavior, learning and memory, expression of GFAP, caspase-3, p53, BDNF, and NMDA receptor in animals subjected to chronic unpredictable stress (CUS). METHODS: After applying 21 days of chronic unpredictable stress, male rats received intraperitoneal (IP) of ketamine (5 mg/kg) and then were exposed to ELF-EMF (10-Hz, 10-mT exposure conditions) for 3 days (3 h per day) and behavioral assessments were performed 24 h after the treatments. Instantly after the last behavioral test, the brain was extracted for Nissl staining, immunohistochemistry, and real-time PCR analyses. Immunohistochemistry (IHC) was conducted to assess the effect of ketamine and ELF-EMF on the expression of astrocyte marker (glial fibrillary acidic protein, GFAP) in the CA1 area of the hippocampus and medial prefrontal cortex (mPFC). Also, real-time PCR analyses were used to investigate the impacts of the combination of ketamine and ELF-EMF on the expression of caspase3, p53, BDNF, and NMDA receptors in the hippocampus in rats submitted to the CUS procedure. Results were considered statistically significant when p < .05. RESULTS: Our results revealed that the combination of ketamine and ELF-EMF increased depression-like behavior, increased degenerated neurons and decreased the number of GFAP (+) cells in the CA1 area and mPFC, incremented the expression of caspase-3, and reduced the expression of BDNF in the hippocampus but showed no effect on the expression of p53 and NMDA-R. CONCLUSIONS: These results reveal that combining ketamine and ELF-EMF has adverse effects on animals under chronic unpredictable stress (CUS).

Improving Swallowing Function and Ability in Post Stroke Dysphagia: A Randomized Clinical Trial.

Post-stroke dysphagia is a prevalent, life threatening condition. Scientists recommended implementing behavioral therapies with new technologies such as transcranial direct current of stimulation (TDCS). Studies showed promising TDCS effects, and scientists suggested the investigation of the effectiveness of different montages. Supramarginal gyrus (SMG) is important in swallowing function. Our study aimed to investigate the effectiveness of stimulating SMG in improving post-stroke dysphagia. Forty-four patients finished the study (a randomized, double-blind one). All of them received behavioral therapy. The real group received anodal (2 mA, 20 min) stimulation on the intact SMG, and the sham group received the same for 30 s (5 sessions). Patients were assessed with Functional Oral Intake Scale (FOIS) and Mann Assessment of Swallowing Ability (MASA) after treatment and at one-month follow-up. The results showed that the difference between groups at baseline was not significant. According to MASA both groups improved significantly during the time (p-value < 0.001). The improvement in the real group was significantly higher than in the sham group after treatment (p-value = 0.002) and after one-month follow-up (p-value < 0.001). According to FOIS, most of the patients in the real group (72.70%) reached level 6 or 7 after one-month follow-up which was significantly higher than the sham group (31.80%, p-value = 0.007). In conclusion, TDCS applied to the scalp's surface associated with SMG localization may improve swallowing function in the stroke patients with dysphagia.

Effects of Moderate-Intensity Interval Training on Gene Expression and Antioxidant Status in the Hippocampus of Methamphetamine-Dependent Rats.

Methamphetamine (METH) can cause neurotoxicity and increase the risk of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. This study aimed to investigate the effect of moderate-intensity interval training (MIIT) on gene expression and antioxidant status of the hippocampus of METH-dependent rats. Thirty-two male Wistar rats were randomly divided into four equal groups (n = 8): saline, METH, MIIT, and METH + MIIT. METH was injected intraperitoneally at 5 mg/kg for 21 days. The MIIT(interval running) was performed on the treadmill 5 days a week for 8 weeks. Morris water maze test was performed to measure learning and memory. Then, the hippocampal tissue was extracted to evaluate changes in gene expression and biochemical enzymes. The data were analyzed using one-way and two-way ANOVA methods at p < 0.05. The results showed that METH injection significantly reduced spatial memory and antioxidant enzymes and increased the expression of α-synuclein (α-syn), cyclin-dependent kinase 5 (CDK5), tau, and phosphorylated tau (p-tau) genes compared to the saline group. MIIT significantly increased spatial memory and antioxidant enzymes. However, it reduced α-syn, CDK5, tau, and p-tau expression. Thus, this study depicted that methamphetamine-dependent rats with memory deficits have lower antioxidant enzyme levels and higher expression of α-syn, CDK5, tau, and p-tau genes, and that an 8-week MIIT may have beneficial effects on the memory impairments as well as antioxidant status and gene expression in male rats.

The effect of gallic acid on memory and anxiety-like behaviors in rats with bile duct ligation-induced hepatic encephalopathy: Role of AMPK pathway.

Objective: Hepatic encephalopathy (HE) is a serious neurological syndrome which is caused by acute and chronic liver diseases. In this study, the effect of gallic acid (GA) as an activator of AMP-activated protein kinase (AMPK) on memory and anxiety-like behaviors in rats with HE caused by bile duct ligation (BDL) was investigated. Materials and Methods: The rats were randomly divided into the following eight groups (n=7): sham; BDL; BDL+GA 20 mg/kg; BDL+GA 30 mg/kg; sham+dorsomorphin or compound C (CC) (as AMPK inhibitors); BDL+CC; BDL+GA 20 mg/kg+CC; and BDL+GA 30 mg/kg+CC. The rats received GA once daily by gavage for four weeks, and dorsomorphin 6.2 µg per rat was administered on a daily basis via bilateral intraventricular injection for four weeks. Behavioral tests including novel object recognition (NOR), open field and Morris water maze (MWM) were used to evaluate anxiety and memory in the rats. Results: Examining some parameters of NOR and MWM tests showed that memory performance was significantly reduced in the BDL versus the sham group, and in the BDL+CC versus the sham+CC group (p<0.05). GA intake improved memory in the GA-receiving groups compared with the BDL and BDL+CC groups (p<0.05). Examining some parameters of open field test showed that anxiety was significantly increased in the BDL versus the sham group, and the BDL+CC versus the sham+CC group (p<0.05). GA intake reduced anxiety in GA-receiving groups compared with the BDL+BDL+CC group (p<0.05). Conclusion: GA was effective in improving cognitive and anxiety-like behaviors through activating AMPK.

Effect of High-Intensity Interval Training on Cardiac Apoptosis Markers in Methamphetamine-Dependent Rats.

Chronic methamphetamine use increases apoptosis, leading to heart failure and sudden cardiac death. Previous studies have shown the importance of high-intensity interval training (HIIT) in reducing indices of cardiac tissue apoptosis in different patients, but in the field of sports science, the molecular mechanisms of apoptosis in methamphetamine-dependent rats are still unclear. The present article aimed to investigate the changes in cardiac apoptosis markers in methamphetamine-dependent rats in response to HIIT. Left ventricular tissue was used to evaluate caspase-3, melusin, FAK, and IQGAP1 gene expression. Rats were divided into four groups: sham, methamphetamine (METH), METH-control, and METH-HIIT. METH was injected for 21 days and then the METH-HIIT group performed HIIT for 8 weeks at 5 sessions per week. The METH groups showed increased caspase-3 gene expression and decreased melusin, FAK, and IQGAP1 when compared to the sham group. METH-HIIT showed decreased caspase-3 and increased melusin and FAK gene expression compared with the METH and METH-control groups. The IQGAP1 gene was higher in METH-HIIT when compared with METH, while no difference was observed between METH-HIIT and METH-control. Twenty-one days of METH exposure increased apoptosis markers in rat cardiac tissue; however, HIIT might have a protective effect, as shown by the apoptosis markers.

The combination of endurance exercise and SGTC (Salvia-Ginseng-Trigonella-Cinnamon) ameliorate mitochondrial markers' overexpression with sufficient ATP production in the skeletal muscle of mice fed AGEs-rich high-fat diet.

BACKGROUND: Skeletal muscle mitochondria is one of the most important affected sites of T2DM and its molecular mechanism is yet to be elucidated. Some recent theories believed that mitochondrial markers are upregulated in response to high fat induced T2DM; however, the reasons and the affected factors are still uncertain. In this regard, we aimed to investigate the effect of high fat induced T2DM on mitochondrial markers of skeletal muscle, and an herbal component along with endurance exercise, as probable treatments, in AGE-rich high-fat diet (AGEs-HFD) induced T2DM mice. METHODS: T2DM was induced by 16 weeks of AGEs-HFD consumption in male C57BL/6 mice, followed by 8 weeks of drugs ingestion and endurance exercise treatments (n = 6 in each group and total number of 42 mice). The herbal component was an aquatic extract of Salvia officinalis, Trigonella foenum-graecum, Panax ginseng, and Cinnamomum zeylanicum, termed "SGTC". We then examined the relative expression of several mitochondrial markers, including Ppargc1α, Tfam, and electron transport chain genes and ATP levels, in skeletal muscle samples. RESULTS: T2DM was successfully induced according to morphological, biochemical, and molecular observations. All mitochondrial markers, including Ppargc1a, Tfam, Cpt2, and electron transport chain genes, were upregulated in T2DM group compared to controls with no significant changes in the ATP levels. Most mitochondrial markers were downregulated by drug treatment compared to T2DM, but the ATP level was not significantly altered. All mitochondrial markers were upregulated in exercised group compared to T2DM with mild increase in the ATP level. The Ex + SGTC group had moderate level of mitochondrial markers compared to T2DM, but the highest ATP production. CONCLUSION: The highly significant overexpression of mitochondrial markers may be in response to free fatty acid overload. However, the lack of significant change in the ATP level may be a result of ROS generation due to electron leakage in the AGEsRAGE axis and electron transport chain. Almost all treatments ameliorate mitochondrial markers' overexpression. The SGTC appears to regulate this with its antioxidant properties. Instead, exercise upregulated mitochondrial markers efficiently; however, the most efficient results, i.e. the most ATP production among the treatments, were observed in the Ex + SGTC group.

Promising Effects of Naringenin and Melatonin against Hepatic Encephalopathy Impairments Induced by Bile Duct Ligation in Male Rats.

BACKGROUND: Bile duct ligation (BDL) is used for evaluating the protective effects of different agents with anti-inflammatory and antioxidant properties against the liver and brain damages. Naringenin (N) and melatonin (M) are used as protectants in various models of diseases. AIMS: In the current research, the combinational effects of these well-known anti-inflammatory and antioxidants agents were investigated against cerebral injuries induced by BDL in male rats. METHODS: The animals were distributed into the following groups: Sham, BDL + Vehicle and BDL+ N + M. Neuronal damages were evaluated using biochemical, motor behavioral tasks and morphological assessments. RESULTS: Based on the data, BDL resulted in decreasing locomotor activity, which was reversed by N and M. Morphological study confirmed that BDL led to neurodegeneration in the cortex of the rats, and the N and M treatment preserved cortical neurons. In addition, immunohistochemical (IHC) study of the rat cortex showed that BDL resulted in increasing the activated astrocytes, and the N and M treatment reduced the number of activated cells. CONCLUSION: These results obviously depicted combinational therapy with N and M to exert positive effects in the BDL rats, probably due to their synergistic anti-inflammatory and antioxidant activities.

Chronically Pre-treatment of Pistachio Alters the Morphology of CA1 Hippocampus Neurons Following Transient Focal Cerebral Ischemia in Male Wistar Rats.

BACKGROUND: Consumption of antioxidants is effective on reducing the damage caused by cerebral ischemia. OBJECTIVES: We investigated the effect of Pistacia vera (pistachio) pretreatment on the morphology of the cornu ammonis (CA1) region of hippocampus neurons of the rats' hippocampus following transient focal cerebral occlusion of the middle cerebral artery (MCA). METHODS: In this study, 30  male Wistar rats were divided into 3 groups of control, ischemia, and pretreatment with pistachio (fed with pistachio at 6% of the diet for a five-week duration before the right MCA occlusion). Neurological scores of the rats were assessed using Baderson rating. Thereafter, the animals' balance and muscle power were assessed by Rotarod and forelimb wire-grip strength tests, respectively. Finally, histopathological and morphometrical characteristics of hippocampal neurons were studied using Hematoxylin-Eosin method. RESULTS: Neurological scores of the ischemia group significantly decreased compared to the control group (p<0.05), while pretreatment with pistachio significantly improved Baderson rating scores compared to the ischemia group (p<0.05). Although stroke significantly decreased the balance and muscular strength in the studied rats compared to the normal rats (p<0.05), pistachio's exposure significantly increased the balance and muscular strength compared to the ischemia group (p<0.05). Additionally, a significant decrease was observed in the volume of stroke and neuronal degradation in the pistachio-treated rats compared with the ischemia group (p<0.05). CONCLUSIONS: Pistachio consumption reduces the volume of infarction and neuronal damage and improves neurological disorders after ischemia. Therefore, pretreatment with pistachio would have a protective effect against stroke.

Hippocampal Astrocyte Response to Melatonin Following Neural Damage Induction in Rats.

INTRODUCTION: Brain injury induces an almost immediate response from glial cells, especially astrocytes. Activation of astrocytes leads to the production of inflammatory cytokines and reactive oxygen species that may result in secondary neuronal damage. Melatonin is an anti-inflammatory and antioxidant agent, and it has been reported to exert neuroprotection through the prevention of neuronal death in several models of central nervous system injury. This study aimed to investigate the effect of melatonin on astrocyte activation induced by Traumatic Brain Injury (TBI) in rat hippocampus and dentate gyrus. METHODS: Animals were randomly divided into 5 groups; Sham group, TBI group, vehicle group, and melatonin-treated TBI groups (TBI+Mel5, TBI+Mel20). Immunohistochemical method (GFAP marker) and TUNEL assay were used to evaluate astrocyte reactivity and neuronal death, respectively. RESULTS: The results demonstrated that the astrocyte number was reduced significantly in melatonin-treated groups compared to the vehicle group. Additionally, based on TUNEL results, melatonin administration noticeably reduced the number of apoptotic neurons in the rat hippocampus and dentate gyrus. CONCLUSION: In general, our findings suggest that melatonin treatment after brain injury reduces astrocyte reactivity as well as neuronal cell apoptosis in rat hippocampus and dentate gyrus.

Minocycline Mitigation of Tremor Syndrome and Defect of Cognitive and Balance Induced by Harmaline.

INTRODUCTION: Minocycline has anti-inflammatory, anti-apoptotic, and anti-oxidant effects. Preclinical data suggest that minocycline could be beneficial for treating common neurological disorders, including Parkinson disease and multiple sclerosis. METHODS: In this study, the effects of minocycline on harmaline-induced motor and cognitive impairments were studied in male Wistar rats. The rats were divided into four groups of ten animals each. Harmaline was used for the induction of Essential Tremor (ET). Minocycline (90 mg/kg, IP) was administered 30 minutes before the saline or harmaline. Tremor intensity, spontaneous locomotor activity, passive avoidance memory, anxiety-related behaviors, and motor function were assessed in the rats. RESULTS: The results showed that minocycline could recover tremor intensity and step width but failed to recuperate the motor balance. The memory impairments observed in harmaline-treated rats were somewhat reversed by administration of minocycline. The cerebellum and inferior olive nucleus were studied for neuronal degeneration using histochemistry and transmission electron microscopy techniques. Harmaline caused ultrastructural changes and neuronal cell loss in inferior olive and cerebellar Purkinje cells. Minocycline exhibited neuroprotective changes on cerebellar Purkinje cells and inferior olivary neurons. CONCLUSION: These results open new therapeutic perspectives for motor and memory impairments in ET. However, further studies are needed to clarify the exact mechanisms.

Inhibition of protease-activated receptor 1 (PAR1) ameliorates cognitive performance and synaptic plasticity impairments in animal model of Alzheimer's diseases.

INTRODUCTION: Alzheimer's disease (AD) is a progressive brain disorder accompanied with synaptic failures and decline in cognitive and learning processes. Protease-activated receptor 1 (PAR1) is the major thrombin receptor in the brain that is implicated in synaptic plasticity and memory formation. In the current study, we hypothesized that inhibition of PAR1 would theoretically prevent amyloid beta (Aß) accumulation in the brain and then contribute to reduce risk of AD. The aim of the present study was to evaluate the effect of PAR1 inhibition by using SCH (as an inhibitor of PAR1) on spatial learning, memory, and synaptic plasticity in the CA1 region of the hippocampus in rat model of Alzheimer's disease. METHODS: For the induction of Alzheimer's disease, amyloid beta (Aß) 1-42 was injected in the CA1 region of the hippocampus. The rats were divided into four groups: group I (surgical sham); group II rat mode of Alzheimer's disease (AD); group III (SCH) (25 µg/kg) intraperitoneally (i.p.), and group IV (AD + SCH). After 14 days of protocol, the rats in group III received SCH and 30 min after injection behavioral and electrophysiological tests were performed. Learning and memory ability was assessed by Morris water maze and novel object recognition tests. Extracellular evoked field excitatory postsynaptic potentials (fEPSP) were recorded in the stratum radiatum of the CA1 area. RESULTS: Our results showed that AD rats showed impairments in learning and memory, and long-term potentiation (LTP) was not induced in these rats. However, injection of SCH overcame the AD-induced impairment in LTP generation in the CA1 area of the hippocampus and improved learning and memory impairment.

Ovarian hormones prevent methamphetamine-induced anxiety-related behaviors and neuronal damage in ovariectomized rats.

Methamphetamine (METH) may cause long‒lasting neurotoxic effects and cognitive impairment. On the other hand, the ovarian hormones estrogen and progesterone have neuroprotective effects. In the current study, we aimed to examine the effects of estrogen and progesterone on anxiety‒like behavior and neuronal damage in METH‒exposed ovariectomized (OVX) rats. Three weeks after ovariectomy, the animals received estrogen (1 mg/kg, i.p.), or progesterone (8 mg/kg, i.p.), or estrogen plus progesterone (with the same doses), or vehicle during 7 consecutive days (days 22-28). On day 28, OVX rats were exposed to a single‒day METH regimen (6 mg/kg, four s.c. Injections, with 2 h interval) 30 min after the hormone treatment. The next day (on day 29), the animals were assessed for anxiety‒related behaviors using the open field and elevated plus‒maze tasks. The animals were then sacrificed and brain water content, cell apoptosis and expression of IL-1ß were evaluated. The findings showed that treatment with estrogen or progesterone alone in METH‒exposed rats significantly improved hyperthermia, anxiety‒like behavior, neuronal damage, and inflammation in the CA1 area. Also, treatment with estrogen plus progesterone improved hyperthermia and brain edema. Taken together, the findings suggest that treatment with ovarian hormones can partially prevent hyperthermia and anxiety‒related behaviors induced by METH in OVX rats, which could be accompanied by their neuroprotective effects in the hippocampus.

Biogenic selenium nanoparticles target chronic toxoplasmosis with minimal cytotoxicity in a mouse model.

Introduction. Nanoparticles (NPs) have numerous biological benefits due to their large surface-volume ratio and convenient entry into cells compared to other particles. Previous research has shown the antimicrobial properties of biogenic selenium NPs (SeNps) and their effects on cellular immunomodulatory cytokines that play a key role in controlling infections.Aim. This study aimed to evaluate the therapeutic effects of SeNPs against chronic toxoplasmosis in mice.Methodology. Infected mice with Toxoplasma gondii (Tehran strain) were orally treated with SeNPs at doses of 2.5, 5 and 10 mg kg-1 once a day for 14 days. On the fifthteenth day, the mean number of brain-tissue cysts and the mRNA levels of TNF-α, IL-12, IL-10, IFN-γ and inducible nitric oxide synthase (iNOS) in the mice of each group were recorded. Moreover, serum clinical chemistry factors in the treated mice were examined to determine the safety of SeNPs.Results. The mean number of tissue cysts was significantly (P<0.001) decreased in mice treated with SeNPs in a dose-dependent manner compared with the control group. The mRNA levels of inflammatory cytokines were significantly increased in mice treated with SeNPs at a dose of 10 mg kg-1 compared with the control subgroup (P<0.05). No significant variation (P>0.05) observed in clinical chemistry parameters among the mice in the control subgroup compared with those treated with SeNPs.Conclusion. The findings demonstrated the therapeutic effects of SeNPs with no considerable toxicity against latent toxoplasmosis in the mouse model. Nevertheless, further studies are obligatory to reveal the exact anti-Toxoplasma mechanisms of SeNPs.