Evaluation of the relationship between serum interleukin-1ß levels and expression of inflammasome-related genes in patients with COVID-19.

BACKGROUND: Inflammasomes are a group of molecules that are strongly involved in causing inflammation. This study aimed to evaluate the expression of NLR family pyrin domain containing 1 (NLRP1), NLRP3, and Apoptosis-associated speck-like protein containing a CARD (ASC) as well as their association with serum level of interleukin (IL)-1ß in patients with coronavirus disease 2019 (COVID-19). METHODS: Thirty COVID-19 patients and 30 healthy subjects (HS) were recruited. Peripheral blood specimens were collected from subjects to assess NLRP1, NLRP3, and ASC gene expression by Real time-PCR technique. Serum levels of IL-1ß were also measured via the enzyme-linked immunosorbent assay (ELISA). RESULTS: The findings showed no significant differences in serum IL-1ß level between COVID-19 patients and the HS group. mRNA expression of ASC (P = 0.008) and NLRP1 (P = 0.03) gene had a significant increase in COVID-19 patients compared to HS, while there was no significant increase in the expression of NLRP3 between the studied group. There were significant correlations between patient's data and expression levels of NLRP1, NLRP3, IL-1ß, and ACS. CONCLUSIONS: NLRP1 and ASC may have a more critical role in the generation of the active form of IL-1ß in COVID-19 patients compared to NLRP3. However, serum levels of IL-1ß in patients did not show a significant increase, which may be due to the patient's condition and the application of virus escape mechanisms through impaired NLRP3 expression and its malfunction.

The prevalence and associated factors of overweight/obesity and abdominal obesity in South-eastern of Iran: a cross-sectional study based on Rafsanjan cohort study.

BACKGROUND: Obesity has become a major health issue in both high and middle-income countries, increasing the risk of cardiovascular diseases and all-cause mortality. Risk of obesity is related to both unchangeable factors such as genetics and gender, and modifiable lifestyle factors. Most importantly, finding the major modifiable lifestyle factors which contribute to obesity may provide valuable benefits to every society. This study aimed to determine the association of demographic and lifestyle parameters with overweight/obesity and abdominal obesity in a population of Iranian adults. METHODS: In this cross-sectional study, adult participants of Rafsanjan Cohort Study (RCS) (as one of the district areas of the PERSIAN cohort (Prospective Epidemiological Research Studies in IrAN) included the study population. RCS is a population-based prospective cohort of men and women aged 35-70 years, launched in August 2015. Individuals were recruited from four urban and suburban areas of Rafsanjan, south-eastern of Iran. Trained experts interviewed each participant and completed the related questionnaires about his/her socioeconomic status, demography, anthropometric features, personal habits, physical activity and medical history. Multinomial logistic regression models were used to examine the relationships between overweight/obesity/abdominal obesity and associated factors. RESULTS: From 9980 participants, 1974 (42.42%) males and 2115 (39.70%) females were overweight, 784 (16.85%) males, 2223 (41.73%) females were obese and 1895 (40.73%) males and 989 (18.57%) females were normal weight. Also, 832 (17.9%) males and 4548 (85.4%) females had abdominal obesity and 3819 (82.1%) males and 778 (14.6%) females didn't have abdominal obesity. Based on the adjusted multiple logistic regression, overweight/obesity (BMI > 25) was associated with age > 45, female gender, education ≥ 13 years, heavy physical activity, wealth status index (WSI), alcohol consumption, current cigarette smoking and opium consumption compared to reference group. Also, odds of abdominal obesity displayed a significant association with age > 45, female gender, education > 5 years, physical activity, WSI, current cigarette smoking, alcohol and opium consumption compared to reference group. CONCLUSIONS: Our results recommend local public health strategies that promote training the society on the health benefits of avoiding alcohol, getting more physical exercise and gaining more personal education on the health-threatening lifestyle.

The profile of Rafsanjan Cohort Study.

Owning the largest human-made jungle of pistachio, the second largest copper mine, and being located on the trade route of opium transit, distinguish Rafsanjan from many other cities in Iran. The environmental exposures and lifestyle factors associated with these characteristics of Rafsanjan, have raised concern about possible health outcomes for individuals living in and around this city. Thus, local health authorities initiated the Rafsanjan Cohort Study (RCS), as part of the prospective epidemiological research studies in IrAN (PERSIAN). RCS is a population-based prospective cohort of men and women aged 35-70 years, launched in August 2015. Individuals from diverse socioeconomic levels and lifestyles were recruited from four urban and suburban areas of Rafsanjan (participation rate 67.42%). Questionnaire-based interviews regarding demographics, dietary and environmental exposures, medical and occupational history, as well as anthropometric measurements were completed for all participants. Additionally, bio-specimens (blood, urine, hair, and nail) were collected, and dental and eye examinations were performed. The enrollment phase ended in December 2017, and a 15-year follow-up is planned. A total of 9990 individuals were enrolled in RCS (53.41% females). About 26% of men are pistachio farmers. The baseline prevalence of major non-communicable disease (NCD) risk factors such as cigarette smoking, alcohol consumption and opium use were 25.45%, 10.02%, and 23.81%, respectively. The mean ± SD of other common risk factors are as follows: body mass index (27.83 ± 4.89 mm Hg), systolic blood pressure (107.18 ± 17.56 mm Hg) diastolic blood pressure (71.13 ± 10.83), fasting blood sugar (113.27 ± 39.11 mg/dL) and plasma cholesterol (198.78 ± 41.89 mg/dL). These results indicate a concerning prevalence of NCD risk factors in Rafsanjan city, warranting further detailed investigations, particularly regarding the association of NDC with agricultural/industrial pollutants and drug abuse.

The effect of intra-striatal administration of GPR55 agonist (LPI) and antagonist (ML193) on sensorimotor and motor functions in a Parkinson's disease rat model.

OBJECTIVE: G protein-coupled receptor 55 (GPR55) is an orphan G protein-coupled receptor with various physiological functions. Recent evidence suggests that this receptor may be involved in the control of motor functions. Therefore, in the present study, we evaluated the effects of intra-striatal administration of GPR55 selective ligands in a rat model of Parkinson's disease. METHODS: Experimental Parkinson was induced by unilateral intra-striatal administration of 6-hydroxydopamine (6-OHDA, 10 µg/rat). L-α-lysophosphatidylinositol (LPI, 1 and 5 µg/rat), an endogenous GPR55 agonist, and ML193 (1 and 5 µg/rat), a selective GPR55 antagonist, were injected into the striatum of 6-OHDA-lesioned rats. Motor performance and balance skills were evaluated using the accelerating rotating rod and the ledged beam tests. The sensorimotor function of the forelimbs and locomotor activity were assessed by the adhesive removal and open field tests, respectively. RESULTS: 6-OHDA-lesioned rats had impaired behaviours in all tests. Intra-striatal administration of LPI in 6-OHDA-lesioned rats increased time on the rotarod, decreased latency to remove the label, with no significant effect on slip steps, and locomotor activity. Intra-striatal administration of ML193 also increased time on the rotarod, decreased latency to remove the label and slip steps in 6-OHDA-lesioned rats mostly at the dose of 1 µg/rat. CONCLUSIONS: This study suggests that the striatal GPR55 is involved in the control of motor functions. However, considering the similar effects of GPR55 agonist and antagonist, it may be concluded that this receptor has a modulatory role in the control of motor deficits in an experimental model of Parkinson.

Transient receptor potential ankyrin 1 (TRPA1)-mediated toxicity: friend or foe?

Transient receptor potential (TRP) channels have been widely studied during the last decade. New studies uncover new features and potential applications for these channels. TRPA1 has a huge distribution all over the human body and has been reported to be involved in different physiological and pathological conditions including cold, pain, and damage sensation. Considering its role, many studies have been devoted to evaluating the role of this channel in the initiation and progression of different toxicities. Accordingly, we reviewed the most recent studies and divided the role of TRPA1 in toxicology into the following sections: neurotoxicity, cardiotoxicity, dermatotoxicity, and pulmonary toxicity. Acetaminophen, heavy metals, tear gases, various chemotherapeutic agents, acrolein, wood smoke particulate materials, particulate air pollution materials, diesel exhaust particles, cigarette smoke extracts, air born irritants, sulfur mustard, and plasticizers are selected compounds and materials with toxic effects that are, at least in part, mediated by TRPA1. Considering the high safety of TRPA1 antagonists and their efficacy to resolve selected toxic or adverse drug reactions, the future of these drugs looks promising.

Correlation of Dietary Intake and Helicobacter pylori Infection with Multiple Sclerosis, a Case-Control Study in Rafsanjan, Iran, 2017-18.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system. Some environmental factors, such as Helicobacter pylori infection (HPI), are likely to be considered a protective factor in MS. Dietary intake may provide exposure to or have protective effects for MS. The present study aimed to determine the relationship between serum anti-H. pylori IgG antibody (HPIA) level and dietary intake in patients with MS referred to the MS Clinic in Rafsanjan city, Iran. METHODS: The present case-control study was conducted on 97 patients with MS and 95 controls. The two groups had no significant difference in age and gender (p > 0.05). HPIA was checked, and the food frequency questionnaire was completed in both groups to measure nutritional intake. All data were analyzed by the SPSS 20 software using independent t-test, Chi-Square, Mann-Whitney U test, and correlation. RESULTS: The median serum HPIA level was significantly lower in MS cases than in controls. Furthermore, the median consumption of glutamic acid, arginine, serine, aspartic acid, alanine, proline, and caffeine was significantly lower in MS cases than in controls. A significant positive correlation was found between the levels of linoleic acid, lactose, Ca, molybdenum, galactose, leucine, and valine, and the level of HPIA in controls. CONCLUSION: Our study results demonstrated that some dietary nutrients had correlations with MS and HPI. Therefore, professionals from multiple disciplines must find which foods contain these dietary nutrients in future studies.

The effect of Wi-Fi electromagnetic waves on neuronal response properties in rat barrel cortex.

There is a growing number of studies on the possible biological effects of Wi-Fi radiations on nervous system. In this study we investigated the effect of Wi-Fi exposure on single neuron responses to natural stimuli by using whisker to barrel pathway. This study was done on 29 male Wistar rats. Neuronal spontaneous activity and ON and OFF responses to displacement of principal whisker (PW), adjacent whisker (AW) and combination of PW-AW stimulation (as natural stimuli) were recorded in barrel cortex of anaesthetised rats. A D-link Wi-Fi device was used for 1 h exposure to 2.4 GHz microwaves in data mode (18.2 dBm and 44% for power and duty cycle). A condition test ratio (CTR) was calculated for assessing neuronal integrative properties. Wi-Fi radiations decreased CTR for ON responses. However, neuronal spontaneous activity and ON and OFF responses were not significantly changed following exposure to Wi-Fi signals. The results of this study demonstrated that exposure to Wi-Fi radiation could modulate integrative responses to natural stimuli in barrel cortex.

Impact of opium dependency on clinical and neuropsychological indices of multiple sclerosis patients.

The aim of this study was to determine the effect of opium on clinical and neuropsychological parameters in multiple sclerosis (MS) patients with substance dependency. A cross-sectional study was conducted on MS patients in Rafsanjan, Iran. Forty opium-addict MS patients (10 males and 30 females) aged between 18 and 50 years were compared with 40 MS patients with no addiction. Word-Pair Learning, Mini-Mental State Examination (MMSE), Wisconsin Card-Sorting Test (WCST), Depression, Anxiety, Expanded Disability Status Scale (EDSS), Fatigue, and the Multiple Sclerosis Functional Composite (MSFC) were measured and compared in the two groups. The comparison of two groups showed a significant increase trait anxiety (P < 0.001), fatigue (P = 0.009) and significant decrease in the executive function (P = 0.003), MMSE (P = 0.003), and working memory (P < 0.001) in addicted MS. It indicates the better efficiency of processing in the non-addicted MS patients. The MSFC z-score also was significantly higher in the non-addicted group (P < 0.001). The opium addiction has a negative impact on the clinical and neuropsychological outcome in MS patients.

The effect of intracerebroventricular administration of orexin receptor type 2 antagonist on pentylenetetrazol-induced kindled seizures and anxiety in rats.

BACKGROUND: Current antiepileptic drugs are not able to prevent recurrent seizures in all patients. Orexins are excitatory hypothalamic neuropeptides that their receptors (Orx1R and Orx2R) are found almost in all major regions of the brain. Pentylenetetrazol (PTZ)-induced kindling is a known experimental model for epileptic seizures. The purpose of this study was to evaluate the effect of Orx2 receptor antagonist (TCS OX2 29) on seizures and anxiety of PTZ-kindled rats. RESULTS: Our results revealed that similar to valproate, administration of 7 µg/rat of TCS OX2 29 increased the latency period and decreased the duration time of 3rd and 4th stages of epileptiform seizures. Besides, it significantly decreased mean of seizure scores. However, TCS OX2 29 did not modulate anxiety induced by repeated PTZ administration. CONCLUSION: This study showed that blockade of Orx2 receptor reduced seizure-related behaviors without any significant effect on PTZ-induced anxiety.

Melatonin as an endogenous regulator of diseases: The role of autophagy.

Melatonin has long been known for its apparent effects on sleep and circadian rhythm. It may participate as a possible therapeutic agent in neurodegenerative, cardiovascular, and endocrine disorders as well. Autophagy is a lysosomal degradation process that occurs in response to starvation and other stresses. Recent studies have reported that melatonin may modulate the autophagy process. We reviewed the current literature that has reported on how different diseases and/or experimental models change autophagy parameters. We also discussed the effect of melatonin on autophagy parameters in the central nervous, cardiovascular, gastrointestinal and endocrine systems as reported in nonclinical studies. Moreover, the molecular targets for melatonin are discussed in details. In summary, melatonin has been reported to enhance significant protective effects in different in vitro and in vivo studies either through enhancement or inhibition of the autophagy process. Melatonin holds promise in the treatment of several major diseases. Regulation of autophagy by melatonin is a determinant parameter that should be considered in the future studies.

Heterogeneous effects of cholecystokinin on neuronal response properties in deep layers of rat barrel cortex.

Cholecystokinin (CCK) is one of the most studied neuropeptides in the brain. In this study, we investigated the effects of CCK-8s and LY225910 (CCK2 receptor antagonist) on properties of neuronal response to natural stimuli (whisker deflection) in deep layers of rat barrel cortex. This study was done on 20 male Wistar rats, weighing 230-260 g. CCK-8s (300 nmol/rat) and LY225910 (1 µmol/rat) were administered intracerebroventricularly (ICV). Neuronal responses to deflection of principal (PW) and adjacent (AW) whiskers were recorded in the barrel cortex using tungsten microelectrodes. Computer controlled mechanical displacement was used to deflect whiskers individually or in combination at 30 ms inter-stimulus intervals. ON and OFF responses for PW and AW deflections were measured. A condition-test ratio (CTR) was computed to quantify neuronal responses to whisker interaction. ICV administration of CCK-8s and LY225910 had heterogeneous effects on neuronal spontaneous activity, ON and OFF responses to PW and/or AW deflections, and CTR for both ON and OFF responses. The results of this study demonstrated that CCK-8s can modulate neuronal response properties in deep layers of rat barrel cortex probably via CCK2 receptors.

The effect of exercise preconditioning on stroke outcome in ovariectomized mice with permanent middle cerebral artery occlusion.

Exercise preconditioning has been shown to be effective in improving behavioral and neuropathological indices after cerebral ischemia. We evaluated the effect of exercise preconditioning, 17ß-estradiol, and their combination on stroke outcome using an experimental model of stroke in ovariectomized (OVX) mice. OVX mice were randomly assigned to 4 groups as follows: control (stroke), exercise (exercise and stroke), estradiol (17ß-estradiol and stroke), and exercise+estradiol (exercise and 17ß-estradiol and stroke). Exercise preconditioning was performed on a treadmill 5 days/week, 40 min/day, at a speed of 18 m/min for 4 weeks. 17ß-estradiol was gavaged (40 µg/kg per day) for 4 weeks. Stroke was induced by permanent middle cerebral artery occlusion (pMCAO), and neurological deficits were evaluated 1, 2, and 7 days after stroke. Then, the serum concentrations of matrix metalloproteinase-9 (MMP-9) and interleukin-10 (IL-10) and infarct volumes were assessed. Exercise preconditioning and 17ß-estradiol induced a better outcome compared with the control ischemic mice, which was manifested by decrease in MMP-9, increase in IL-10, diminished infarct volume, and improved neurological deficits. Concomitant administration of 17ß-estradiol and exercise also significantly improved these parameters. Exercise preconditioning or administration of 17ß-estradiol alone or in combination before pMCAO induced significant neuroprotection in OVX mice.

Effect of TPMPA (GABAC receptor antagonist) on neuronal response properties in rat barrel cortex.

GABAC receptors are ligand-gated chloride channels and have important roles in some neurological functions like vision. Recent investigations demonstrated that these receptors are also expressed in the somatosensory cortex. In this study, we investigated the effect of (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) (GABAC receptor antagonist) on the properties of the neuronal response to natural stimuli (whisker deflection) in deep layers of rat barrel cortex. Twenty-eight male Wistar rats, weighing 230-260 g, were used in this study. TPMPA (100 µmol/rat) was administered intracerebroventricularly (ICV). Neuronal responses to deflection of principal (PW) and adjacent (AW) whiskers were recorded in barrel cortex using tungsten microelectrodes. A computer-controlled mechanical displacement was used to deflect whiskers individually or in combination at 30 ms inter-stimulus intervals. ON and OFF responses for PW and AW deflections were measured. A condition-test ratio (CTR) was computed to quantify neuronal responses to whisker interactions. Our data suggest that ICV administration of TPMPA increased neuronal spontaneous activity, ON and OFF responses to PW, and/or AW deflections. However, CTR for neither ON nor OFF responses changed following TPMPA administration. The results of this study demonstrated that inhibition of GABAC receptors by TPMPA can modulate neuronal response properties in rat barrel cortex.

Short-term effects of troxerutin (vitamin P4) on muscle fatigue and gene expression of Bcl-2 and Bax in the hepatic tissue of rats.

In the current study, the effects of troxerutin (TRX) on muscle fatigue and gene expression of Bcl-2 and Bax in the hepatic tissue of rats was investigated. Forty male Wistar rats were randomly divided into 4 groups and designated as control and TRX treatment at 75 (TRX75), 150 (TRX150), and 300 mg/kg per day (TRX300). The treated groups and control group received TRX and water orally for 7 days. After an exhaustive swimming test on the 7th day, all animals were euthanized immediately and several biochemical parameters related to fatigue and gene expression of Bcl-2 and Bax in the hepatic tissue were measured. Our results showed that the exhaustion swimming time in the TRX300 groups significantly increased 1.2-fold compared with the control group (P < 0.001). TRX300 significantly reduced ALT (P < 0.05) activity and increased liver SOD activity compared with the control group (P < 0.01). Additionally, TRX significantly reduced the liver mRNA expressions of Bax (P < 0.001) and increased the Bcl-2/Bax ratio (P < 0.001) compared with the control group. Based on our data, TRX possesses anti-apoptotic and hepatoprotective action following exhaustive swimming exercise.

The effect of Wi-Fi electromagnetic waves in unimodal and multimodal object recognition tasks in male rats.

Wireless internet (Wi-Fi) electromagnetic waves (2.45 GHz) have widespread usage almost everywhere, especially in our homes. Considering the recent reports about some hazardous effects of Wi-Fi signals on the nervous system, this study aimed to investigate the effect of 2.4 GHz Wi-Fi radiation on multisensory integration in rats. This experimental study was done on 80 male Wistar rats that were allocated into exposure and sham groups. Wi-Fi exposure to 2.4 GHz microwaves [in Service Set Identifier mode (23.6 dBm and 3% for power and duty cycle, respectively)] was done for 30 days (12 h/day). Cross-modal visual-tactile object recognition (CMOR) task was performed by four variations of spontaneous object recognition (SOR) test including standard SOR, tactile SOR, visual SOR, and CMOR tests. A discrimination ratio was calculated to assess the preference of animal to the novel object. The expression levels of M1 and GAT1 mRNA in the hippocampus were assessed by quantitative real-time RT-PCR. Results demonstrated that rats in Wi-Fi exposure groups could not discriminate significantly between the novel and familiar objects in any of the standard SOR, tactile SOR, visual SOR, and CMOR tests. The expression of M1 receptors increased following Wi-Fi exposure. In conclusion, results of this study showed that chronic exposure to Wi-Fi electromagnetic waves might impair both unimodal and cross-modal encoding of information.

Protective effect of hydroalcoholic extract of Pistacia vera against gentamicin-induced nephrotoxicity in rats.

PURPOSE: Pistacia vera is a plant of the family Anacardiaceae found in Central and West Asia. P. vera nut (Pistachio) possess multiple pharmacological effects such as antimicrobial, anti-hyperlipidemia, antioxidant and anti-inflammatory. This study is designed to evaluate the protective effect of the hydroalcoholic extract of pistachio on gentamicin-induced nephrotoxicity in rats. METHODS: Nephrotoxicity was induced in rats by intraperitoneal injection of gentamicin (100 mg/kg/day for 7 days). Hydroalcoholic extract of pistachio (10, 50 and 100 mg/kg/p.o) was administered for 7 days. The nephroprotective activity was evaluated by determining creatinine clearance, serum creatinine, urine volume, urine glucose and blood urea nitrogen (BUN) levels. The kidneys were processed for histopathological examinations and all specimens were examined for morphologic parameters involving tubular degeneration, tubular necrosis and tubule interstitial nephritis. RESULTS: Results showed a significant increase in the levels of serum creatinine, urine volume, urine glucose and BUN and decrease of creatinine clearance by gentamicin (GA) administration. Co-administration with pistachio extract showed reduction in the levels of serum creatinine, urine volume, urine glucose and BUN and increase of creatinine clearance in all doses but the most significant alteration was observed in doses of 100 mg/kg. Also, the nephroprotective effect of the GA was confirmed by the histological examination of the kidneys. CONCLUSION: The study revealed the nephroprotective effect of the hydroalcoholic extract of pistachio. These findings suggest that pistachio treatment may attenuate renal dysfunction and structural damage through the reduction of oxidative stress and inflammation in the kidney.

Effects of naringin on physical fatigue and serum MMP-9 concentration in female rats.

CONTEXT: Oxidative stress has a critical role in the development of physical fatigue and activation of matrix metalloproteinases-9 (MMP-9). Naringin (Nar) is a bioflavonoid that has antioxidant activity and suppresses MMP-9 expression. OBJECTIVE: The present study evaluates the anti-fatigue activity of Nar on physical fatigue and serum MMP-9 concentration in rats. MATERIALS AND METHODS: Fifty female Wistar rats were randomly divided into five groups (n = 10); a control group, vehicle group and three Nar treatment groups. The Nar treated groups received different doses of Nar (40, 80 and 160 mg/kg/day) for 30 days. On the 30th day, rats were sacrificed immediately after exhaustive swimming test. Serum MMP-9 concentration and several biochemical parameters related to fatigue were measured. RESULTS: Exhaustive swimming time in the Nar-80 group significantly increased 1.78-, 1.53-, 1.5- and 1.3-fold compared with the control, vehicle, Nar-40 and Nar-160 groups, respectively. In addition, exhaustive swimming time in the Nar-160 group significantly increased 1.36-fold compared with the control group. Nar-80 significantly decreased LDH activity by 60.45% and 57.47% compared with the vehicle and control groups, respectively. Furthermore, Nar-80 and Nar-160 increased blood glucose levels by 19.56% and 18.38% compared with the control group, respectively. Nar-80 and Nar-160 significantly decreased serum MMP-9 concentration by 61.57% and 83.39% compared with the control group, respectively. CONCLUSION: Based on our data, Nar has anti-fatigue effects which may be attributed to its property in modulating energy metabolism and reducing serum MMP-9 concentration. Thus, Nar may be a promising agent for the treatment of physical fatigue.

The Possible Role of Toll-Like Receptor 4 in the Pathology of Stroke.

Stroke is a prevalent and dangerous health problem, which triggers an intense inflammatory response to Toll-like receptor (TLR) activation. TLRs are the essential components of the response of the innate immunity system, and, therefore, they are one of the key factors involved in recognizing pathogens and internal ligands. Among TLRs, TLR4 significantly participates in the induction of inflammation and brain functions; hence, it has been hypothesized that this molecule is associated with several immune-related brain diseases such as stroke. It has also been proved that animals with TLR4 deficiency have higher protection against ischemia and that the absence of TLR4 reduces neuroinflammation and injuries associated with brain trauma. TLR4 deficiency may play a neuroprotective role in the occurrence of stroke. This article reviews recent information regarding the impact of TLR4 on the pathogenicity of stroke.

Involvement of central TRPV1 receptors in pentylenetetrazole and amygdala-induced kindling in male rats.

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel that is involved in modulation of diverse physiological processes. The role of this receptor in epilepsy has not been studied well. Therefore, we investigated the role of central TRPV1 receptors on the development of pentylenetetrazole (PTZ) and amygdala-induced kindling in rats. Male Wistar rats received subconvulsive dose of PTZ intraperitoneally, every other day. TRPV1 receptor agonist, OLDA and its antagonist, AMG-9810 were injected intracerebroventricularly 30 min prior to PTZ administration. In electrical kindling, stimulating and recording electrodes were implanted in the right amygdala of male rats. After kindling, the effect of TRPV1 receptor agonist or antagonist on afterdischarge duration (ADD), latency to the onset of bilateral forelimb clonuses (S4L) and duration of loss of equilibrium (stage 5 seizures, S5D) were measured. The results demonstrated that, OLDA at the doses of 0.01, 0.1 and 1 µg/rat, significantly accelerated the incidence of all seizure stages, increased S5D and decreased S4L in the PTZ model of kindling. Also, in amygdala kindling, S5D and ADD were significantly reduced following the administration of AMG-9810. In contrast, OLDA significantly aggravated the indices of seizure in both models of epileptic seizure. This study demonstrated that central TRPV1 receptors may be involved in the development of electrical and PTZ-induced kindling.

Morphine Reduces Expression of TRPV1 Receptors in the Amygdala but not in the Hippocampus of Male Rats.

BACKGROUND: Chronic use of opioids usually results in physical dependence. The underlying mechanisms for this dependence are still being evaluated. Transient receptor potential vanilloid type 1 (TRPV1) are important receptors of pain perception. Their role during opioid dependence has not been studied well. The aim of this study was to evaluate the effect of morphine-dependence on the expression of TRPV1 receptors in the amygdala and CA1 region of the hippocampus. METHODS: This study used four groups of rats. Two groups of rats (morphine and morphine+naloxone) received morphine based on the following protocol: 10 mg/kg (twice daily, 3 days) followed by 20, 30, 40 and 50 mg/kg (twice daily), respectively, for 4 consecutive days. Another group received vehicle (1 ml/kg) instead of morphine given using the same schedule. The morphine+naloxone group of rats additionally received naloxone (5 mg/kg) at the end of the protocol. The control group rats received no injections or intervention. The amygdala and CA1 regions of the morphine, saline-treated and intact animals were isolated and prepared for real-time PCR analysis. RESULTS: Administration of naloxone induced withdrawal signs in morphine-treated animals. The results showed a significant decrease in TRPV1 gene expression in the amygdala (P<0.05) but not the CA1 region of morphine dependent rats. CONCLUSION: TRPV1 receptors may be involved in morphine-induced dependence.