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Showing 29 results for Subject: Neurodegeneretive diseases

Farshad Homayouni Moghadam, Hojatoallah Alaie, Khadije Karbalaie, Somayeh Tanhaei, Mohammad Hossein Nasr Esfahani, Hossein Baharvand,
Volume 11, Issue 3 (12-2007)
Abstract

Introduction Cholinergic system is one of the important systems of mammalian CNS. Cholinergic neurons distributed in brain and spinal cord and contributed to principal functions like: consciousness, learning and memory, and motor control. In this study we investigated the differentiation potentiality of mouse embryonic stem cells toward cholinergic neurons. The aim of this study was to evaluate the effect of sonic hedgehog (Shh), Retinoic Acid (RA), LIF, IL6 and NGF on differentiation of neural progenitor cells (NPCs), produced by lineage selection method, to cholinergic neurons. Material and methods Royan B1, mouse embryonic stem cells derived from C57BL/6 strain was used to produce aggregates. Aggregates were cultured in serum free medium to produce nestin positive or NPCs, then cell expansion was achieved by treatment with EGF and FGF2. Following withdrawal of EGF and FGF2, the cells were further cultured in presence or absence of differentiation factors in serum containing medium. Relative number of neurons and cholinergic neurons were assessed by immunohistochemical procedure using antibodies against MAP2, B-tubulin3, and ChAT. Results Data obtained show that around 70% of cells were B-tubulin3 positive. We found ChAT immunoreactivity in cultured cells in both treated and control groups. Conclusion This study shows that some of the neurons produced by lineage selection method are cholinergic neurons, and the percentage of cholinergic neurons increased after treatment by Shh, LIF and RA.
Adele Jafari, Javad Fahanik-Babaei, Afsaneh Eliassi, Reza Saghiri,
Volume 17, Issue 1 (3-2013)
Abstract

Introduction: Alzheimer’s disease is a progressive neurodegenerative disorder, characterized by impairment of memory and changes in behavior and personality. Recent evidence suggests that mitochondrial channels play important roles in memory disorders. Accordingly, the biophysical properties of a single potassium channel were investigated in the brain mitochondrial inner membrane of rat with Alzheimer’s disease. Methods: In the male Wistar rats (220-250 g), Alzheimer’s disease was induced by intracerebroventricular injection of amyloid beta 1-42 (4μg/μL). After two weeks, the brain mitochondrial inner membranes were extracted. Vesicles were incorporated into lipid bilayer membranes, and single potassium channel properties were investigated. Also, purity of the cell fraction was tested by Western blotting. Protein samples were probed with specific antibodies. Results: Based on our previous data, mitochondrial inner membrane has a potassium channel with a main conductance 93 pS which was 4-AP sensitive and voltage-insensitive at -50 to +40 mV. In the present study, it was demonstrated that the channel conductance was increased to 114 pS in Alzheimer’s disease. In addition, the currentvoltage relationship showed an inward rectification. Western blotting and antibodies directed against various cellular proteins revealed that the extracted material contains only mitochondria. Conclusion: Our data showed that the biophysical properties (gating, conductance and activities) of potassium channel were significantly altered in Alzheimer’s disease. Based on these findings, we propose that the brain mitochondrial potassium channels are involved in Alzheimer’s disease, and it can be considered as a target for therapeutic plans.
Shahram Shahmohamadi, Akbar Hajizadeh Moghaddam, Maryam Khosravi,
Volume 17, Issue 2 (7-2013)
Abstract

Introduction: Oxidative stress is the result of imbalance between free radicals and the antioxidant defense mechanisms of the body. Oxidative stress in brain causes dysfunction of brain activities, destruction of neurons, and disorders like Alzheimer disease. In this experimental study, we examined the protective effect of Salvia officinalis L. against oxidative stress induced by intracerebroventricular injection of streptozotocin in male rats. Methods: In the experimental research, Wistar rats were divided into control, sham, and experimental groups. Experimental groups received 25, 50 and 100 mg/kg body weight of hydroalcoholic extract of Salvia officinalis intraperitoneally. After two weeks, surgical procedure was performed on sham and experimental groups and after one week of recovery, streptozotocin was injected intracerebroventricularly (i.c.v-STZ) at 3 mg/kg. Brain hemispheres were separated after four weeks. Finally, superoxide dismutase (SOD) and catalase (CAT) levels were measured in brain hemispheres. Results: In the group receiving STZ, CAT and SOD levels were significantly decreased compared to the control group (P<0.001), whereas intraperitoneal injection of different doses of Salvia officinalis leaves extract significantly increased SOD and CAT levels compared to STZ group (P<0.001). Conclusion: These data show that antioxidant effects of Salvia officinalis L. could prevent oxidative stress induced by i.c.v.-STZ injection in the brains of male rats.
Shabnam Ghaffari, Homeira Hatami Nemati, Gholamreza Dehghan,
Volume 17, Issue 3 (10-2013)
Abstract

Introduction: Cognitive dysfunction is recognized as a significant feature of multiple sclerosis (MS). Oxidative stress plays an important role in the pathogenesis of MS. Toxic demyelination by ethidium bromide (EB) is one of the common methods for induction of MS, which leads to neuronal death by production of free radicals and enhancement of oxidative stress burden. According to previous pharmacological studies, saffron extract acts as a free radical scavenger. Accordingly, in the present study the effect of short-term microinjection of saffron extract on the process of spatial memory and lipid peroxidation in the hippocampus was assessed in an experimental model of MS. Methods: One week after MS induction by EB (0.01 %), animals of the experimental group were treated by saffron extract (5 and 10 μg/rat) for 3 consecutive days. Following the treatment period, Morris Water Maze test was carried out and hippocampi of both sides were dissected and used for measurement of a lipid peroxidation marker (MDA) in the end. Results: Based on the results of the present study, short-term treatment by saffron extract significantly ameliorated spatial memory in experimental models of MS (P<0.05). MDA in the saffron treated group showed a significant reduction compared to the control MS animals (P<0.01). Conclusion: It seems that treatment with saffron extract is able to prevent memory and learning reduction, through inhibition of lipid peroxidation in an experimental model of MS. However, evaluation of beneficial effects of saffron on the spatial memory and its role in preventing or treating cognitive deficits in MS patients, requires much more extensive molecular studies.
Mohammad Sophiabadi, Negin Fraidouni, Ayda Faraji, Tahereh Dargahi, Hassan Yaghubi-Dust, Hashem Haghdoost-Yazdi,
Volume 17, Issue 3 (10-2013)
Abstract

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.
Sedigheh Khanjani Jelodar, Mohammad Reza Bigdeli,
Volume 17, Issue 3 (10-2013)
Abstract

Introduction: Huntington's disease is a neurodegenerative disorder in which an increase in the global oxidative stress and a decrease in the antioxidant defense system are observed. Olea europaea's main phenolic components include oleuropein, dimethyl oleuropein, ligstroside and phenolic oleosides, which can be more than 140 mg per gram of fresh olives and 60-90 mg per gram of dried olive leaves. These phenolic components have great antioxidant and neuroprotective properties. We aimed to study the neuroprotective effects of pretreatment with olive leaf extract on the behavioral signs and antioxidant enzymatic activity in the brains of Huntington animal models. Methods: Rats were divided into 4 groups in separate cages. The first and the second groups received distilled water orally. The third and the fourth groups were gavaged by75 and 150 mg/Kg/day of olive leaf extract, respectively. To induce Huntington’s disease, the animals were intraperitoneally injected with3-NP for 6 days. Results: Pretreatment with olive leaf extract exerts neuroprotective effects and significantly reduces neurological disorders and increases superoxide dismutase, glutathione reductase and catalase activities. Conclusion: Although more studies are required to explain the healing mechanism of olive leaf extract, it seems to exert its effects via protecting neurons through its antioxidant properties and its ability to increase enzyme activities including superoxide dismutase, glutathione reductase, catalase.
Zahra Rabiei, Mahmoud Rafieian,
Volume 17, Issue 4 (1-2014)
Abstract

Introduction: Alzheimer’s Disease (AD) is a chronic neurological disorder characterized by memory impairment, cognitive dysfunction, behavioral disturbances, and deficits in activities of daily living. AD has been found to be associated with a cholinergic deficit in the post-mortem brain characterized by a significant decrease in acetylcholine amount and loss of cholinergic neurons of the nucleus basalis of Meynert (NBM). This study investigated the effect of Zizyphus jujuba (ZJ) extract on motor activity in NBM-lesioned rat model of AD and intact rats. Methods: In this study, 49 wistar rats were divided into 7 groups. Rats received bilateral electrolytic lesions of the NBM. The control and sham group received distilled water while NBM-lesioned groups received ZJ extract via gastric gavage for 20 days. Intact rats received ZJ extract for 20 days without any surgery. The motor activity assessed with rota-rod apparatus. Data were compared using one way ANOVA followed by LSD post test. Results: ZJ extract for 20 days improved motor activity in NBM-lesioned rats and intact rats that received extract at the dose of 1000 mg/kg. Conclusion: Results suggest that ZJ extract can improve the motor coordination both in NBM-lesioned rats and in intact rats.
Sima Nasri, Zahra Hajializadh, Saeed Esmaeili-Mahani,
Volume 17, Issue 4 (1-2014)
Abstract

Introduction: Uncontrolled diabetes mellitus could lead to neuropathy in central and peripheral nerve tissues and one of its main signs can be hyperalgesia and motor coordination defect. Due to the blood glucose lowering effect of Thymus species and the presence of polyphenolic compounds with high antioxidant capacity, in this study the effect of Thymus caramanicus jalas extract was investigated on animal model of diabetes-induced neuropathy. Methods: In the present study development of hyperalgesia was examined by tail-flick and rota-rod tests, in streptozotocin-induced diabetic male wistar rats (subcutaneous injection). Animals were given Thymus caramanicus jalas extract (50, 100, 150 and 200 mg/kg) for 6 weeks. The levels of blood glucose were measured at the beginning and the end of the experimental period. Results: Blood glucose levels in diabetic animals which received Thymus extract at the doses of 150 and 100 mg/kg was reduced as compared to the pretreatment levels (p<0.05 and p<0.01, respectively). Untreated diabetic rats showed lower threshold in pain sensation and motor deficit compared with the control animals. However, tail-flick latency and ability to stay on rota-rod were significantly decreased in diabetic animals that received 100 mg/kg (p<0.01) and 150 mg/kg (p<0.001) of extract. Conclusion: The data show that Thymus caramanicus jalas extract has ability to reduce serum glucose levels and attenuate hyperalgesia and motor deficit induced by diabetes in rats. The mechanisms of this effect may be related to (at least in part) the attenuation of blood glucose and prevention of neural damage.
Sepide Tarbali, Shiva Khezri, Reza Heidari,
Volume 17, Issue 4 (1-2014)
Abstract

Introduction: Consumption of vitamin D3 is effective to reduce intensity of autoimmune diseases such as multiple sclerosis. Neurons of the central nervous system are constantly exposed to reactive oxygen species and these factors play a key role in the destruction of myelin and damage of axons. The hippocampus is a vital center for learning and memory in central nervous system. This area is extremely vulnerable to neurodegenerative diseases and oxidative damage. In the present study the effects of vitamin D3 on learning, spatial memory and lipid peroxidation following demyelination of rat hippocampal CA1 neurons was investigated. Methods: For demyelination induction, 2μl lysolecithin was injected into the CA1 area of rat brain using stereotaxic surgery. After induction of demyelination, animals received 5 μg/kg vitamin D3 for 7 days. The learning and spatial memory of rats were investigated by radial maze. The extent of demyelination in hippocampus was studied using myelin specific Luxol fast blue staining. On day 7, lipid peroxidation was evaluated by Esterbauer and cheeseman methods. Results: The results of this study showed that administration of vitamin D3 caused significant improvement of spatial learning and memory compared to the group receiving lysolecithin alone (p<0.001). Levels of lipid peroxidation in group treated with vitamin D3 showed significant reduction compared to the group receiving lysolecithin alone (p<0.01). Conclusion: Vitamin D3 acts as an antioxidant agent and caused improvement in learning and spatial memory through reduction of demyelination and lipids peroxidation products.
Seyyed Rasoul Zaker, Siamak Beheshti, Rezvan Aghaie, Maryam Noorbakhshnia,
Volume 18, Issue 4 (1-2015)
Abstract

Introduction: Olibanum improves memory in different models of learning. However, the effect of olibanum on models of Alzheimer’s disease has been less studied. In the present study, the effect of olibanum on memory in normal rats and in a rat model of Alzheimer disease induced by intracerebroventricular injections of streptozotocin was evaluated. Methods: Rats received an aqueous extract of olibanum (50, 100 and 300 mg/kg) via gavage, acutely 30 minutes before the test and chronically for 21 consecutive days before assessment of memory racall. In two other groups of animals, two guide cannulas were inserted into the lateral ventricles under stereotaxic surgery. One group received bilateral injections of streptozotocin (1.5 mg/kg/2 μl/side) in the first and third days of surgery. The other group received artificial cerebrospinal fluid. Fourteen days after surgery, learning was evaluated. Two other groups of animals received olibanum (50 mg/kg) or its solvent, for 21 days beginning from one week before injections of streptozotocin. Results: Acute administration of olibanum did not affect learning parameters, but chronic administration of it (50 mg/kg) improved memory retrieval. Streptozotocin increased number of necessary stimulations for induction of short term memory, but decreased step through latency, significantly. In animals which received streptozotocin, olibanum increased step through latency, significantly. Conclusion: Olibanum reduces the risk of Alzheimer’s disease induced by streptozotocin. Further studies with emphasis on active constituents of olibanum may result in development of drugs capable of decreasing probability of Alzheimer’s disease occurrence.
Vahid Pirhajati Mahabadi, Mansoureh Movahedin, Zohreh Mazaheri, Saeed Semnanian, Javad Mirnajafi_zadeh, Mehrdad Faizi,
Volume 19, Issue 1 (3-2015)
Abstract

Introduction: Noradrenergic cells in LC participate in the process of cortical activation and behavioral arousal. The evidence suggests that locus ceoruleus (LC) plays an important role in the sleep-wake cycle. The aim of this study was stereological estimation of cavity caused by lesion and assessment of sleep stages after bilateral lesion of the LC. Materials and Methods: Male Wistar rats weighting 250-275 gr were divided into four groups (control: n=6, sham: n=6, lesion1: n=6 and lesion2: n=6). 6 hydroxydopamine (6 OHDA) (2μg/0.5μl and 4μg/1μl) was sterotaxically injected bilaterally into LC to produced lesion. For sleep recording 3 EEG and 2 EMG electrodes were implanted respectively in the skull and dorsal neck muscle. Recordings were taken before and 7, 21 and 42 days after lesion. After 7 weeks, Rats first were anesthetized and then their brains were removed and cut in 7 μm serial sections and stained with cresyl violet. The volume of LC and the lesion induced cavity were evaluated through the stereological technique. Results: Lesion - induced cavity volume (0.5 μl) was restricted to LC, whereas Another group (1 μl), total LC and structures adjacent to the LC were also damaged. A significant decrease was seen in non-rapid eye movement (NREM) and paradoxical sleep (PS) stages and a significant increase was seen in duration of wake and paradoxical sleep without atonia (PS-A) in lesion group in comparison with control and sham groups. Conclusion: The results of this study demonstrate 2μg/0.5μl 6-OHDA is suitable dose for LC lesion and bilateral lesion of LC causing disrupt wake, NREM ,PS and also produce the PS-A.
Bahar Naghavi Gargari, Mehrdad Behmanesh, Mohammad Ali Sahraian,
Volume 19, Issue 1 (3-2015)
Abstract

Introduction: Multiple sclerosis is a chronic inflammatory disease of central nervous system. The etiology of MS is slightly known, but genetic and environmental factors are reported. Vitamin D regulates gene expression and affects target cell functions. The aim of this study was to investigate the expression variation of IL-2 and IL-4 genes under vitamin D supplementation in patients with multiple sclerosis. Materials and Methods: In this study, blood samples were drawn from 32 patients before and after treatment with vitamin D. Quantitative real time PCR was used to measure IL-2 and IL-4 gene expression levels. Correlation analysis between the expression levels of genes and serum vitamin D, the Expanded Disability Status Scale (EDSS) as well as other clinical features of patients with MS was performed. Results: No significant difference of IL-2 and IL-4 genes expression level was observed with vitamin D supplementation. We did not find significant correlation between IL-2 and IL-4 mRNA levels and EDSS score in multiple sclerosis patients. Conclusion: We did not find any difference between the expression of IL-2 and IL-4 genes before and after treatment with vitamin D that it may have some effects on the prevention of multiple sclerosis through other inflammatory factors and signaling pathways.
Mohammad Hossein Esmaeili, Tahereh Dargahi, Hashem Haghdoost-Yazdi,
Volume 19, Issue 2 (5-2015)
Abstract

Introduction: A large body of evidence points to oxidative stress as prime candidate mediating the behavioral impairments and memory deficits in Alzheimer's disease (AD). It has been demonstrated that hyperoxia preconditioning activates complex endogenous neuroprotective mechanisms including an increase in capacity of antioxidant defence mechanisms. The aim of this study was to investigate the beneficial effects of normobaric hyperoxia preconditioning in streptozotocin (STZ)- induced memory impairment in rats. Materials and Methods: Male Wistar rats were first exposed to air with high oxygen concentration (>90%) or atmospheric air for 24 hours and then STZ (3 mg/kg) was bilaterally infused in lateral ventricles of the brain. Two weeks later Morris Water Maze (MWM) test was performed to assess spatial learning and memory consolidation. Results: STZ increased escape latency (P<0.05), distance and number of crossed quadrants (P<0.05) especially on 1st and 2nd days. However, hyperoxia preconditioning significantly attenuated STZ-induced learning and memory deficits during training sessions in the MWM (P<0.05). Preconditioning also increased time spent and swimming distance in the target quadrant in probe test (P<0.05). However, hyperoxia preconditioning had no effect on the swimming speed. Conclusion: Hyperoxia preconditioning significantly attenuated STZ-induced impairments in spatial learning and memory. These results suggest that hyperoxia may have a potential therapeutic effect at the early stage of AD and possibly the prevention of memory deficits.


Ekram Mohammadi, Mohammad Reza Bigdeli,
Volume 19, Issue 2 (5-2015)
Abstract

Introduction: The purpose of this study was to determine Na-Ca exchanger 2, 3 (NCX2, 3) protein level changes during 2, 5, 10, 15 days after induction of normobaric hyperoxia (HO) preconditioning. Materials and Methods: Rats were divided in two experimental groups. The first group was exposed to 95% inspired HO for 4 h/day for 6 consecutive days (HO). The second group acted as control, and was exposed to 21% oxygen in the same chamber. Each main group was subdivided to middle cerebral artery occlusion (MCAO-operated) and intact (without any surgery) subgroups. After 2, 5, 10 and 15 days from pretreatment, MCAO-operated subgroups were subjected to 60 min of right MCAO. After 24 hours reperfusion, neurologic deficit score (NDS) and infarct volume (IV) were measured in MCAO-operated subgroups. The NCX 2, 3 expression levels of core, penumbra and subcortex regions were assessed in sham-operated and intact subgroups. Results: Expression of NCX 2, 3 proteins were increased in penumbra (P=0.000, P=0.002), core (P=0.001, P=0.033) and just NCX3 was increased in subcortex (P=0.033) during preconditioning with HO. Neurologic deficit score and infarct volume were decreased with HO preconditioning. These effects of hyperoxia disappeared gradually during 15 days after pretreatment. Conclusion: Although further studies are needed to clarify the mechanisms of time course of neuroprotection, HO durable effects on NCX2, 3 expression, IV and NDS are consistent with an active role in the genesis of ischemic neuroprotection.
Ghorbangol Ashabi, Fariba Khodagholi, Shima Zare-Shahamati, Negar Ghadernezhad, Mona Maleki, Leila Khalaj,
Volume 19, Issue 3 (10-2015)
Abstract

Ischemic brain injury involves a complex sequence of excitetoxic and oxidative events. Metformin is proposed as one of the potential candidates for returning the body to its basic homeostasis in ischemic situations. Metformin can either protect or damage cells by activating AMP-activated protein kinase (AMPK) and its downstream factors so, it has a dual role in the cerebral ischemia context, but more investigations are needed to define its exact underlying mechanism. Herein, we classify the controversial results of metformin therapy in the experimental models of brain ischemia central and peripheral injection of metformin, chronic and acute treatment, pre- and post-treatment with metformin, tissue-specific role of metformin, dose-specific effect of metformin, age-dependent aspects of metformin therapy. Categorizing different types of cerebral ischemia is important in investigating the dual role of metformin. Due to the variations in metformin therapy, it can be used for chronic treatment, but the patients must be informed about its harmful effects. Although the mechanisms in which AMPK protects/degenerates neurons against ischemic stress situation are still unknown.


Svetlana A Ivanova, Olga Yu Fedorenko, Maxim B Freidin, Valentina M Alifirova, Natalia G Zhukova, Irina A Zhukova, Asmar Fy Al Hadithy, Jacobus Rbj Brouwers, Nikolay A Bokhan, Bob Wilffert, Anton Jm Loonen,
Volume 19, Issue 4 (12-2015)
Abstract

Introduction: Long-term levodopa treatment of Parkinson’s disease (PD) is frequently complicated by spontaneously occurring involuntary muscle movements called dyskinesia. The exact pathological mechanism of this complication has not yet been elucidated. We have previously demonstrated that in PD patients the vulnerability to develop peripheral but not orofacial dyskinesia is associated with the presence of two variants of the GRIN2A gene. Moreover, we have shown that in tardive dyskinesia (TD) orofacial dyskinesia is associated with other polymorphisms as compared with peripheral dyskinesia. In the present study we investigate whether the peripheral versus orofacial nature of levodopa-induced dyskinesia (LID) in PD can be explained by considering polymorphisms for dopaminergic and serotonergic receptors. Materials and Methods: 101 Russian patients with PD (38M/63F) were examined. Genotyping was carried out on 19 SNPs for 3 neurotransmitter genes: 10 SNPs for DRD3 gene (rs11721264, rs167770, rs3773678, rs963468, rs7633291, rs2134655, rs9817063, rs324035, rs1800828, rs167771), 1 SNP for DRD4 gene (rs3758653), and 8 SNPs for HTR2C gene (rs6318, rs5946189, rs569959, rs17326429, rs4911871, rs3813929, rs1801412, rs12858300). Results: Genotyping patients with PD and LID revealed that only rs3773678 (DRD3, dominant, p = 0.042) was associated with orofacial dyskinesia. Conclusion: The findings of the current study are not related to LID in PD itself, but to other forms of orofacial dyskinesia in this patient group.


Sajjad Salari, Maryam Bagheri,
Volume 20, Issue 1 (2-2016)
Abstract

Alzheimer's disease (AD) is the most common form of neurodegenerative disorders. Memory loss in an alert person and impairment in the function of language, attention, perception, judgment or problem solving can occur in patients with AD. However, there are some medications in order to delay the debilitating aspects of the disease; but unfortunately, scientists could not found approaches to cure this progressive problem. Hence, in order to investigate the exact mechanisms underlying the disease and to discover novel drugs that can slow the progress or alleviate the clinical symptoms of AD, producing a model which can express the most pathophysiologic and behavioral features of the disease is a desire. Nowadays, there are different animal models developed by use of pharmacologic agents and/or genetic manipulations. In this paper, we aimed to describe different animal models of AD, genetic and pharmacologic, that are mostly used by researchers.


Sharareh Daryani, Alireza Farzaei, Narges Hosseinmardi, Farideh Bahrami, Mahyar Janahmadi,
Volume 20, Issue 2 (5-2016)
Abstract

Introduction: Although aging is the most important risk factor for Alzheimer's disease (AD), there is evidence indicating that neuroinflammation may contribute to the development and progression of the disease. Several studies indicated that minocycline may exert neuroprotective effects in rodent models of neurodegenerative diseases. Nevertheless, there are also other studies implying that minocycline has no positive beneficial effects. Thus, the aim of the present study was to assess the preventive effect of minocycline against Aβ-induced changes in intrinsic electrophysiological properties in a rat model of AD. Methods: The present study extended this line of research by examining whether inhibition of microglial activation may alter the intrinsic electrophysiological properties of CA1 pyramidal neurons in a rat model of Aβ neurotoxicity, using whole cell patch clamp. Results: Findings showed that bilateral injection of the Aβ (1-42) into the prefrontal cortex caused membrane hyperpolarization, action potential (AP) narrowing and after hyperpolarization (AHP) amplitude enhancement. It was also resulted in a faster decay time of AP, higher rheobase current, lower firing frequency and smaller post stimulus AHP amplitude. Administration of minocycline (45mg/kg, i.p) not only failed to prevent Aβ-induced alterations in the intrinsic electrophysiological properties, but also enhanced the effects of Aβ on neuronal firing behavior. Conclusion: It can be concluded that minocycline, as a microglial inhibitor, may enhance the disruption of electrophysiological properties of CA1 pyramidal neurons induced by Aβ neurotoxin, including AP parameters and intrinsic neuronal excitability.


Mina Afhami, Fatemeh Abbaszadeh, Elham Saghaei, Kobra Naseri, Mohammad Javan, Masoumeh Jorjani,
Volume 20, Issue 3 (8-2016)
Abstract

Introduction: Spinal cord injuries are accompanied with significant demyelination of axons and subsequent locomotor dysfunction. To identify the extent of damage following electrolytic lesion of ventrolateral white matter, essential area for initiation of locomotor activity, we assessed demyelination as well as alteration in motor performance. Moreover, the protective effect of estradiol as a candidate treatment for preservation of myelin and locomotor activity after injury was examined due to its anti-apoptotic and anti-inflammatory activities. Methods: A unilateral electrolytic lesion positioned in the right ventrolateral funiculus (VLF) was applied following laminectomy at T8-T9. In the estradiol-treated injury group, animals received a pharmacological single dose of estradiol valerate (4 mg/kg) at 30min post injury. Locomotor function was assessed using rotarod and open field tasks during 4 weeks after injury. Results: Obtained results showed significant demyelination at the site of injury and caudal areas following lesion as well as altered motor performance. Post-spinal cord injury administration of estradiol enhanced white matter maintenance at the site of lesion, restored the level of myelin basic protein (MBP), decreased TUNEL positive cells and improved functional recovery. Conclusion: Taken together, these results indicate that demyelination after lesion in VLF may be a contributing factor to limited motor performance, and suggest that pharmacological doses of estradiol may have an early protective effect through sparing of white matter.


Siamak Beheshti, Azam Soleimanipour,
Volume 21, Issue 1 (2-2017)
Abstract

Introduction: Retinoid signaling has been argued to have favorable effects on Alzheimer's disease (AD). We studied the role of chronic intracerebroventricular (ICV) injection of all-trans retinoic acid (ATRA) on the amyloid-beta (Aβ) model of AD. Methods: Adult male rats weighing 260-330 g were divided into 12 groups of 8 each. Six groups of rats received ATRA (3nM, 30nM, 3μM, 0.3mM, 30mM/rat; ICV) or DMSO 1% (2μl/rat; ICV), bilaterally and in a chronic manner (6 times, twice a week). Forty eight hours following the last injection, memory performance was assessed using a passive avoidance paradigm. One group received Aβ (10μg/rat; ICV), bilaterally. The control group received DMSO 1% (2μl/rat; ICV). Twenty days later memory performance was assessed. Three groups of rats received Aβ (10μg/rat; ICV) and then ATRA (3nM or 30nM/rat; ICV) or DMSO 1%, chronically (6 times, twice a week). Another group received DMSO 1% (2μl/rat; ICV) and then, DMSO 1%, chronically (6 times, twice a week). Results: ATRA at doses 0.3mM and 30mM/rat impaired memory retrieval by decreasing step-through latency (STL) and increasing time spent in the dark compartment (TDC), significantly. However, moderate doses (3nM and 30nM/rat) did not change memory performance. ATRA (30nM/rat) increased STL and decreased TDC and NST in the Aβ-treated rats, significantly compared to the group received Aβ-DMSO 1%. Conclusion: The results propose a potential prophylactic effect of ATRA in the ICV Aβ model of AD and indicate the prominence of retinoic acid signaling as a target for AD prevention.



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