Papers by Hashem Haghdoost-Yazdi
Neurochemical Research, Apr 3, 2018
Epidemiological studies indicate that a higher plasma level of uric acid (UA) associates with the... more Epidemiological studies indicate that a higher plasma level of uric acid (UA) associates with the reduced risk of Parkinson's disease (PD). To confirm the role of UA as a biomarker for PD, we evaluated changes in the serum UA level in the 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonism in rat. For this purpose, 6-OHDA was administered in the medial forebrain bundle by stereotaxic surgery. According to the apomorphine-induced rotational test, the increased intensity of behavioral symptoms as a function of time was associated with the further reduction of UA level. On the other hand, the level of UA increased in the midbrain of the injured hemisphere. The level of reduction in the serum UA level of rats with severe and moderate symptoms was significantly higher than that of rats with mild symptoms. The immunohistofluorescence and biochemical analyses showed that the serum UA level was also correlated with the death of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc), reduced level of striatal dopamine, and severity of oxidative stress in the midbrain. The rats with mild symptoms also showed a significant decrease in TH-positive neurons and striatal dopamine level. These findings suggest a positive correlation between the level of reduction in the serum urate level and severity of 6-OHDA-induced Parkinsonism. In addition, our findings indicated that UA had no marked neuroprotective effects, at least at concentrations obtained in this study. On the other hand, UA was introduced as a biomarker for PD, as a significant decline was observed in the serum UA level of rats with mild behavioral symptoms but with significant dopaminergic cell death in the SNc.
Scientific Journal of Kurdistan University of Medical Sciences
Background and Aim. It has been reported that lithium (Li) has neuroprotective effects in neurode... more Background and Aim. It has been reported that lithium (Li) has neuroprotective effects in neurodegenerative diseases. In this study, we investigated the association between serum Li level and Parkinson's disease induced by 6-hydroxypapamine (6-OHDA) in rats. Material and Methods. 6-OHDA was injected into the medial forebrain bundle by stereotoxic surgery. Apomorphine-induced rotational and cylinder tests were carried out before the toxin injection and in the second and sixth weeks thereafter. Blood samples were collected from the heart of the animals in the seventh week. The survival of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) was determined using immunohistochemistry. Li was measured by ion selective electrode method (ISE). Results. There was no significant difference in the serum Li levels between control and 6-OHDA-treated rats. Based on the severity of the rotational behavior, the 6-OHDA-treated rats were divided into two subgroups: symptomatic (with severe behavioral symptoms) and asymptomatic (with no or mild behavioral symptoms). In the symptomatic and asymptomatic subgroups, SNc DA neuronal loss was 83 ± 16% and 45± 10%, respectively. Serum li level in the asymptomatic subgroup was significantly higher than that in the symptomatic subgroup and control group. Conclusion. Serum Li level increased in the mild to moderate damage to SNc DA neurons but returned to normal value in severe neuronal damage. Therefore, an increase in serum Li level can predict subclinical SNc DA neuronal death and helps in making early diagnosis of PD.
مجله دانش و تندرستي, Dec 17, 2011
Introduction: Systemic injections of morphine have been shown to elicit analgesic responses in fo... more Introduction: Systemic injections of morphine have been shown to elicit analgesic responses in formalin test. However, the locations of central sites that may mediate these effects have not been clearly elucidated. This study assessed the antinociceptive action of morphine after microinjection into the nucleus reticularis paragigantocellularis lateralis (LPGI) in the formalin test in rats. Formalin-induced behaviour is characterized by two phases relevant to acute and tonic. Methods: In this behavioral study, Inflammatory Pain Model by formalin was used in white rats with weight range of 200-300g. Using a stereotaxic apparatus, canulla was inserted into the LPGI. After 1 week recovery, animals were initially submitted to the injection of 50 ml of 2% formalin solution in hind paw. Results: Intra-LPGI microinjection of morphine produced robust inhibition of formalin-evoked behaviour in phase 1, interphase and phase 2 (P<0.001); however, exogenous injection of morphine in the LPGI had no effect on reducing formalin induced nociceptive behaviors Conclusion: The results suggested that morphine plays an anti-nociceptive role in LPGI in phase 1, interphase and late phase of formalin test in rats, which suggests that opioid receptors in the LPGI may be involved in the LPGI-mediated depression of formalin test as inflammatory pain.
Bratislava Medical Journal
BACKGROUND: Using neural stem cells (NSCs) in cell therapy and regenerative medicine is a growing... more BACKGROUND: Using neural stem cells (NSCs) in cell therapy and regenerative medicine is a growing knowledge. In this study, the protective role of carnosic acid and trehalose against H 2 O 2-induced oxidative stress in autophagy induction and apoptosis inhibition in NSCs was investigated. MATERIAL AND METHODS: The bone marrow stromal cells (BMSCs) were isolated from the femur of the rat and differentiated into NSCs using basic fi broblast and epidermal growth factors (bFGF and EGF), and B27 serum free media. To evaluate the autophagy, the P62 protein was assessed by immunocytochemistry and LC3II / LC3I ratio by Western blotting. Further, we used 3-Methyladenine (3-MA), a widely used autophagy inhibitor to study whether combined treatment of 3-MA with carnosic acid and trehalose modulates autophagy in NSCs. For studying apoptosis, the cleaved caspase-3 protein was evaluated. Carnosic acid and trehalose increased the survival of the NSCs. RESULTS: The H 2 O 2 decreased the autophagy and induced apoptosis with increasing time during 24 hours, however, a pre-treatment with 2 μM carnosic acid and trehalose 3 % induced the autophagy proteins (while increasing the LC3II / LC3I ratio and decreasing the P62) and decreased the apoptosis (while decreasing the expression of the cleaved caspase-3). The results showed that the carnosic acid and trehalose increased the survival of NSCs against the oxidative stress caused by H 2 O 2 , decreased apoptosis, and induced autophagy. CONCLUSION: Due to the carnosic acid and trehalose unique properties and its low toxicity, it can be used as an agent in cellular transplantation for reducing oxidative stress and inducing autophagy (Fig. 4, Ref. 37).
Introduction: Transplantation of embryonic ventral mesencephalic (VM) dopamine neurons into the s... more Introduction: Transplantation of embryonic ventral mesencephalic (VM) dopamine neurons into the striatum is a currently explored therapeutic strategy for treatment of patients with patients with Parkinson's disease (PD). However, this strategy has been limited with poor cell survival, generally ranging from 5-20%. In this study, we investigated the effect of potassium channel blocker of tetraethylammonium (TEA) and B vitamins supplementation on the efficacy of cell replacement therapy in the treatment of 6-hydroxydopamine (6-OHDA)-induced Parkinsonism. Methods: Cell suspension was prepared from embryonic day 14 (E14) VM of rat fetuses and was transplanted into striatum of Parkinsonian rats after overnight hibernation with TEA or B vitamins. The Parkinsonian rats were also treated with TEA or B vitamins for two weeks after transplantation. Severity of Parkinsonism was assessed by apomorphine-induced rotational test in several steps before and after transplantation. Results: 1-Transplantation of VM cell suspension significantly decreased behavioral symptoms of Parkinsonism in the apomorphine-induced rotational test. 2-TEA treatment further decreased these symptoms. 3-B vitamins treatment had no additional effect in amelioration of the symptoms. 4-Treatment with both TEA and B vitamins also further decreased behavioral symptoms, which in one post-transplantation test was even more than the effect of TEA alone. Conclusion: TEA, especially in combination with B vitamins supplementation, can increase the efficacy of cell replacement therapy in the 6-OHDA rat PD model.
Background: 4-aminopyridine (4-AP) and tetraethylammonium (TEA) are two potassium channel blocker... more Background: 4-aminopyridine (4-AP) and tetraethylammonium (TEA) are two potassium channel blockers which have shown that have beneficial effects in treating some neurological disorders such as ataxia, Alzheimer and multiple sclerosis. In this study the effect of acute administration of 4-AP and TEA in the treatment of behavioral symptoms of Parkinsonism induced by the toxin 6-hydroxydopamine (6-OHDA) was studied in male rats. Materials & Methods: 6-OHDA was injected into left medial forebrain bundle (MFB) by stereotaxic surgery using Hamilton syringe. Then, in the third week after surgery, the rats before and after drug application were tested for rotational behavior induced by apomorphine. In the fourth week, Rotarod test was performed in the presence of the blockers for six consecutive days. Results: 4-AP at doses 200 and 500 µg/kg had no significant effect, but at dose 1000 µg/kg led to a significant improvement of behavioral symptoms of Parkinsonism in the rotation test. On the other hand, the drug decreased motor performance and motor learning in the Rotarod test. TEA at dose 1 mg/kg was ineffective, but at dose 2 mg/kg caused a significant decrease, and at dose 5 mg/kg caused a significant increase in the number of rotations of the Parkinsonian rats. TEA had no effect on the motor learning in the Rotarod test. Conclusion: The results of this study indicate that 4-AP and TEA, in a dose-dependent manner, weaken some symptoms of Parkinsonism, but worsen some other symptoms.
Metabolic brain disease, 2021
Human studies indicate that Parkinson's disease (PD) associates with disruption in metabolism... more Human studies indicate that Parkinson's disease (PD) associates with disruption in metabolism of glucose and free fatty acids (FFA). Studies have shown that interlukin-1beta (IL-1β) causes hypoglycemia through insulin- independent mechanisms. Here, we investigated association between dopaminergic neuronal death, as the main pathophysiological mechanism underlying PD, and serum levels of glucose, FFA and IL-1β in 6-hydroxydopamine (6-OHDA) animal model of PD. Neurotoxin of 6-OHDA was injected into medial forebrain bundle and multiple behavioral testes were carried out during eight weeks thereafter. Blood was collected before the toxin and in second and eight weeks thereafter. Then, brain of the animals was perfused to assess survival of dopaminergic (DAergic) neurons in substantia nigra by tyrosine hydroxylase (TH) immunohistochemistry. Glucose, FFA and IL-1β levels were determined using calorimetric method and specific ELISA kits. In compare to control, 6-OHDA- treated rats had ...
Journal of Babol University of Medical Sciences, 2014
Neurophysiology, 2018
The effects of combined prenatal stress (including the action of electromagnetic fields, zoo soci... more The effects of combined prenatal stress (including the action of electromagnetic fields, zoo social stress, and immobility on pregnant females) on the learning and memory of offsprings of rats were investigated. Two groups of male and female rats (n = 16 in each) were studied. The animals received prenatally (from 8 to 18 days of gestation) three different stresses as follows: immobilization of pregnant mothers (0.5 h, twice a day by placing in a restrainer), social stress (6 rats kept in a small cage), and exposure to electromagnetic waves (4 h, 0.5 MT, 50 Hz). The learning and memory of rats were assessed two months after birth (2, 6, 24, 48 h and 1-and 2-week-long intervals after training) by using a conditioning avoidance method. Also, expression of the APP gene was investigated in rats using RT-PCR. The prenatal stress suppressed visits of male offsprings to the dark compartment in comparison with the control group, and the difference was significant 2 h after the shock (P < 0.05). These parameters were also reduced in female offsprings of the stressed group, but this difference was insignificant (P > 0.05).The relative expression of the APP gene was also higher in both male and female offsprings (P < 0.05 and 0.01, respectively). Thus, the implemented combined prenatal stress impaired the acquisition process and long-term memory in male offsprings and long-term memory in female offsprings. Also, it may promote deposition of β-amyloid plaques.
Basic and clinical neuroscience, 2014
The formalin test is the most accepted chemical test for evaluation of nociception. It requires t... more The formalin test is the most accepted chemical test for evaluation of nociception. It requires the injection of an adequate amount of formalin into the surface of the hindpaw. Formalin test consists of phase 1 (0-7 min) and phase 2 (15-60) in which the animal shows painful behaviors. These phases are separated with a quiet phase named interphase, in which the nociceptive responses are decreased or completely disappeared. The goal of the current study was to evaluate the effects of swim stress at different heights of water on different phases of the formalin test in male rats. Swim stress decreased nociceptive behaviors in first phase and prolonged interphase or delayed the start of second phase in a water height dependent manner. Swim stress in 25 and 50cm completely abolished the nociceptive behaviors in phase 1. The present results showed different pain modulation during different phases of the formalin test and elucidated the impact of swim stress on duration of interphase. Inte...
Neurological Research, 2011
Objective: Cerebellar Purkinje cells (PCs) fire burst of Na z spikes riding on a Ca 2z spike whic... more Objective: Cerebellar Purkinje cells (PCs) fire burst of Na z spikes riding on a Ca 2z spike which basically involves the same ionic channels and currents establishing the paroxysmal depolarization shift (PDS) discharges. Methods: Intracellular recordings were taken from somata of PCs to explore effects of the epileptogenic drugs of pentylenetetrazol (PTZ), bicuculline methiodide (BCC) and 4-aminopyridine (4-AP) on the firing behavior of these cells. Results: PCs showed spontaneous PDS-like events in presence of these drugs. Generally, PTZ and BCCinduced PDSs were similar in shape and properties but were remarkably different from 4-AP-induced PDSs. Blockade of glutamate transmission inhibited generation of PDSs by PTZ and BCC but it did not affect discharge of PDSs induced by 4-AP. Careful analysis of PDS discharges revealed that they have remarkable differences with normal and 4-AP-induced spontaneous activity. Discussion: Data presented here indicate that PDS discharges in PCs are induced either by the imbalance between excitatory and inhibitory synaptic transmission or by the suppression of 4-AP-sensitive currents.
Introduction: It is known that acute and chronic stress induce hormonal and neuronal changes whic... more Introduction: It is known that acute and chronic stress induce hormonal and neuronal changes which affecting both pain threshold and nociceptive behaviours. Orexin plays an important role in modulation of pain and stress. Considering pain modulation during stress and the role of orexin in pain and stress, orexin might be involved in pain modulation during stress.We evaluated the involvement of orexin receptor-1in acute immobilization stress on the tonic pain model. Methods: Adult male, Wistar rats (200-300 g), placed in a stereotaxic apparatus and canulla were inserted into their left cerebral ventricle. After 1 week of recovery, animals were initially submitted to one session of acute restraint stress (30 min) and immediately submitted to formalin injection in the hind paw to evaluate nociceptive behaviours. Orexin receptor 1 antagonist (SB 334867) was injected intracerebroventricularly, 5 minute before formalin injection, while the solvent was injected in the control group. Results: two percent formalin produced typical biphasic pain responses in rats that was observed for more than 1 hour. Acute exposure to restraint stress reduced the nociceptive behaviour by chemical stimulation in phase 1, interphase and phase 2. The short-term stress induced analgesia was reflected in a decrease in the nociceptive behaviour during phase 1, whereas the long-term stress induced analgesia was reflected in a decrease in the nociceptive behaviours during phase 2. Pretreatment with orexin receptor 1 antagonist (SB 334867) attenuated the antinociceptive behavioral effect of restraint stress. Conclusion: Our results indicate that orexin receptor 1 antagonist attenuated antinociceptive effect of restraint stress assessed by formalin. These findings show that orexin receptor 1 might mediate an opioid-independent stress-induced analgesia.
Introduction: Parkinson is a brain’s degenerative disease. Evidence shows that the levels of homo... more Introduction: Parkinson is a brain’s degenerative disease. Evidence shows that the levels of homocysteine increases in the Parkinson's disease. In this study, the success of cell transplantation was evaluated by comparison between serum homocysteine levels and behavioral symptoms in experimentally Parkinson's induced by 6-hydroxy dopamine (6- OHDA). Methods: This experimental study was conducted in 2014 on male Wistar rats. The rats initially were Parkinsonism through stereotaxic 6- OHDA microinjection into right middle frontal areas of right hemisphere. Parkinson's was confirmed by apomorphine-induced rotation test. Then the rats treated with stem cell transplantation and the effect of treatment was assessed again. The total level of homocysteine was measured before, six weeks after 6- HDOA injection and ten weeks after cell transplantation. Data were analyzed using paired t-tests, ANOVA and Tukey test. Results: The total level of homocysteine didn’t change significantl...
Advanced Pharmaceutical Bulletin, 2015
Scrophularia variegata M. Beib. (Scrophulariaceae) is an Iranian medicinal plant which is used fo... more Scrophularia variegata M. Beib. (Scrophulariaceae) is an Iranian medicinal plant which is used for various inflammatory disorders in traditional medicine. In this study we evaluated the anti-cancer and cytotoxic effects of the Scrophularia variegata (S. variegata) ethanolic extract on the human breast cancer cell line. Methods: The cytotoxicity effect of the extract on MCF-7 cells was evaluated by MTT assay. In addition, Caspase activity, DNA ladder and Cell death were evaluated by ELISA, gel electrophoresis and Annexin V-FITC/PI staining, respectively. Results: The S. variegata extract showed significant effect cytotoxicity on MCF-7 human breast cancer cell line. Treatment with the extract induced apoptosis on the breast cancer cells by cell cycle arrest in G2/M phase. The results indicated that cytotoxicity activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation as well as an increase of the amount of caspase 3 and caspase 9. In addition, the phytochemical assay showed that the extract had antioxidant capacity and also flavonoids, phenolic compounds and phenyl propanoids were presented in the extract. Conclusion: Our findings indicated that S. variegata extract induced apoptosis via mitochondrial intrinsic pathway on breast cancer by cell cycle arrest in G2/M phase and an increase of caspase 3 and caspase 9. However future studies are needed.
Background: Nuclease and caspase enzymes activities which promote death signals and lead to apopt... more Background: Nuclease and caspase enzymes activities which promote death signals and lead to apoptosis are dependent to potassium ions. Objective: The aim of this study was to determine the effect of 4-aminopyridine (4-AP) potassium channel blocker on the animal model of Parkinson's disease. Methods: This experimental study was performed in Qazvin University of Medical Sciences, 2013. Male Rats were received different doses of 4-AP twice daily from half an hour before injection of 6hydroxydopamine (6-OHDA) to 7 or 15 days after that. 6-OHDA was injected into medial forebrain bundle (MFB) in acute model groups and into striatum in chronic model groups. The severity of Parkinsonism was assessed by standard behavioral methods. Data were analyzed using Kruskal-Wallis and Mann Whitney U tests. Findings: In acute model groups, administration of 0.5 mg/kg 4-AP (n=9) had no remarkable effect on behavioral symptoms, but 1 mg/kg 4-AP (n=8) significantly reduced the severity of apomorphine-induced rotations and improved motor learning in rotarod test. In chronic model groups, although 1 mg/kg 4-AP (n=7) significantly reduced the severity of rotations and improved motor learning, but 0.5 mg/kg 4-AP (n=8) was more effective. Conclusion: Pretreatment with 4-AP can reduce 6-OHDA-induced dopaminergic neuron death. Since the chronic model of 6-OHDA is more similar to Parkinson's disease in human, the low dose of 4-AP is recommended for treatment of this disease.
Physiology and Pharmacology, Oct 10, 2013
Introduction: Transplantation of embryonic ventral mesencephalic (VM) dopamine neurons into the s... more Introduction: Transplantation of embryonic ventral mesencephalic (VM) dopamine neurons into the striatum is a currently explored therapeutic strategy for treatment of patients with patients with Parkinson's disease (PD). However, this strategy has been limited with poor cell survival, generally ranging from 5-20%. In this study, we investigated the effect of potassium channel blocker of tetraethylammonium (TEA) and B vitamins supplementation on the efficacy of cell replacement therapy in the treatment of 6-hydroxydopamine (6-OHDA)-induced Parkinsonism. Methods: Cell suspension was prepared from embryonic day 14 (E14) VM of rat fetuses and was transplanted into striatum of Parkinsonian rats after overnight hibernation with TEA or B vitamins. The Parkinsonian rats were also treated with TEA or B vitamins for two weeks after transplantation. Severity of Parkinsonism was assessed by apomorphine-induced rotational test in several steps before and after transplantation. Results: 1-Transplantation of VM cell suspension significantly decreased behavioral symptoms of Parkinsonism in the apomorphine-induced rotational test. 2-TEA treatment further decreased these symptoms. 3-B vitamins treatment had no additional effect in amelioration of the symptoms. 4-Treatment with both TEA and B vitamins also further decreased behavioral symptoms, which in one post-transplantation test was even more than the effect of TEA alone. Conclusion: TEA, especially in combination with B vitamins supplementation, can increase the efficacy of cell replacement therapy in the 6-OHDA rat PD model.
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Papers by Hashem Haghdoost-Yazdi