فهرست مطالب

Physiology and Pharmacology
Volume:21 Issue: 1, Mar 2017

  • تاریخ انتشار: 1395/12/08
  • تعداد عناوین: 9
|
  • Mahmoud Rezaei, Azam Sadeghian, Nahid Roohi, Amir Shojaei, Javad Mirnajafi Zadeh Pages 1-14
    Epilepsy is accompanied with a strong change in neuronal activity not only in excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmission, but also in neuromodulatory agents. Dopaminergic system, as an important neuromodulatory system of the brain, has significant effect on neuronal excitability. In addition, this system undergoes many changes in epileptic brain. Understanding the effects of dopaminergic system in neuronal activities in epileptic brain and knowing the seizure-induced changes in dopaminergic system can shed light into finding the mechanisms involved in epileptogenesis and can help us in finding new treatments for epilepsy. In this review we briefly introduce dopaminergic system and its changes in brain areas which have role in epilepsy. Then, we will focus on the evidences showing the relationship between epilepsy and dopaminergic system.
    Keywords: Epilepsy, Dopaminergic System
  • Nuredin Bakhtiari, Elham Moslemee-Jalalvand, Jahanfard Kazemi Pages 15-24
    We and other studies have elucidated single molecules that can attenuate aging and extend longevity. Indeed, these molecules could prevent age-associated diseases simultaneously and probably extending healthy-life spans. In this review, we discuss recent advances, controversies, opportunities and challenges surrounding ursolic acid (UA) in relationship with aging. In this regard, UA also known as urson, prunol, micromerol and malol is a pentacyclic triterpenoid compound which naturally occurs in a large number of vegetarian foods, medicinal herbs and other plants, including apples and rosemary. Our previous studies for the first time evaluated anti-aging effects of UA. These studies indicated that UA through overexpression of anti-aging biomarkers such as sirtuin (SIRT) 1, SIRT6 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha/beta (PGC-1α/β). Klotho and orexin-A in the brain, skeletal muscle, liver and kidney ameliorates aging and thereby conferring broad health benefits in rodents, primates and possibly human. Taken together, our recent findings advantageously described that UA mimics short-term caloric restriction, exercise and has a potential therapy for age-related diseases. Finally, the prospects for drugs that can deliver at least a subset of the benefits of caloric restriction seems very real.
    Keywords: Ursolic Acid, aging, Sirtuins, PGC-1β- α, Klotho
  • Olga Yu. Fedorenko, Anton J.M. Loonen, Natalya M. Vyalova, А, Nastasiya S. Boiko, Ivan V. Pozhidaev, Diana Z. Osmanova, Lyubov D. Rakhmazova, Nikolay А, . Bokhan, Mikhail V. Ivanov, Maxim B. Freidin, Svetlana А, . Ivanova Pages 25-33
    Introduction
    Hyperprolactinemia is a common serious side effect of antipsychotic medications that are currently used in the treatment of patients with schizophrenia. Pharmacogenetic approaches offer the possibility of identifying patient-specific biomarkers for predicting the risk of this side effect. We investigated a possible relationship between variants (SNPs) in genes for cytochrome 2D6 (CYP2D6), dopamine-2 receptor (DRD2) and serotonin-2C receptor (HTR2C) and antipsychotic drug-induced hyperprolactinemia in patients with schizophrenia.
    Methods
    Overall, 128 Russian patients with paranoid schizophrenia (61F/67M, aged 18-65 y) were included. Serum prolactin concentration was measured with ELISA. DNA analysis and genotyping of CYP2D6 (rs3892097), DRD2 (rs6275) and HTR2C (rs6318) genes was done with StepOnePlus Real-Time PCR System using TaqMan® SNP Genotyping Assays (Applied Biosystems, USA).
    Results
    Our study showed an association of the CYP2D6 (rs3892097) and HTR2C (rs6318) gene polymorphism with hyperprolactinemia in patients with schizophrenia on the background of therapy. No associations were identified between the DRD2 (rs6275) gene polymorphism and the risk of antipsychotic-induced hyperprolactinemia in patients with schizophrenia.
    Conclusion
    Our study confirms a contribution of genetic factors to the antipsychotic-induced hyperprolactinemia in patients with schizophrenia. Further studies are required to unravel the genetic predictors of antipsychotic-induced side effects and to develop the personalized treatment strategies for patients with schizophrenia.
    Keywords: Schizophrenia, Hyperprolactinemia, Antipsychotics, Gene polymorphism
  • Siamak Beheshti, Azam Soleimanipour Pages 34-43
    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.
    Keywords: All-trans retinoic acid, Alzheimer's disease, Amyloid-β, Rat
  • Mahboobeh Aghagolzadeh, Akbar Hajizadeh Moghaddam, Bagher Seyedalipour Pages 44-53
    Introduction
    Oxidative stress seems to play a critical role in the degeneration of dopaminergic neurons in Parkinson’s disease (PD). Antioxidant compounds can deactivate and scavenge free radical. Olive leaves are considered as a useful source of phenolic compounds. Therefore, this study was designed to investigate the effects of methanolic olive leaf extract (OLE) on neurobehavioral activity and antioxidant enzyme activity, malondialdehyde (MDA) and glutathione (GSH) levels in striatum of rats in an experimental model of PD.
    Methods
    The PD was induced in animals by intrastriatal injection of 6-hydroxydopamin unilaterally. Animals were pretreated with the OLE (50, 100 and 150 mg/kg body weight) for 7 weeks, and then behavioral activity (narrow beam and grip testes) and antioxidant parameters were evaluated.
    Results
    In our study behavioral testes showed improvement in motor coordination and balance behavior in rats pretreated with OLE. Furthermore the extract of olive leaf restored the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase) and decreased MDA and increased GSH levels in the brain of rats.
    Conclusion
    Our results suggest that OLE shows a neuroprotective effect in animal models of Parkinson's disease.
    Keywords: Olive leaf extract, Oxidative stress, 6-Hydroxydopamine, Neurobehavioral activity, Parkinson's disease
  • Hamdy M. Embark Pages 54-62
    Introduction
    The cystic fibrosis transmembrane conductance regulator (CFTR) chloride (Cl−) channel is an essential component of epithelial Cl− transport systems in many organs. CFTR is mainly expressed in the lung and other tissues, such as testis, duodenum, trachea and kidney. The ubiquitin ligase neural precursor cells expressed developmentally down-regulated protein 4-2 (Nedd4-2) has previously been shown to regulate abundance of several channel and carrier proteins in the plasma membrane, an effect reversed by glucocorticoid dependent kinase 1 (SGK1).
    Methods
    The present study was thus performed to elucidate the sensitivity of CFTR to regulation by Nedd4-2 and the serum and SGK1. To this end, the CFTR was heterologously expressed in oocytes alone or together with Nedd4-2 or the SGK1. The cRNAs encoding CFTR, Nedd4-2 and/or the constitutively active S422DSGK1 have been injected into Xenopus oocytes. The activity of CFTR was measured by the two-electrode voltage-clamp technique and CFTR-mediated currents were elicited by the application of forskolin and IBMX (F/I).
    Results
    As a result, forskolin/IBMX treatment triggered cAMP-stimulated ion currents (IcAMP) in Xenopus oocytes expressing CFTR cRNA, but not in oocytes injected with water (control). Co-expression of Nedd4-2 markedly down-regulates the cAMP-stimulated ion current (IcAMP), an effect reversed by Co-expression of the constitutively active S422DSGK1. In Xenopus oocytes co-expressing CFTR with S422DSGK1 the cAMP-stimulated ion current (IcAMP) was similar to that in Xenopus oocytes expressing CFTR alone.
    Conclusion
    The present observations suggest that CFTR is a target for the ubiquitin ligase Nedd4-2, which is inactivated by the SGK1.
    Keywords: CFTR, Trafficking, Xenopus laevis oocyte expression, SGK1, Nedd4-2
  • Kameni Poumeni Mireille, Dzeufiet Djomeni Paul Desire, Bilanda Danielle Claude, Mengue Ngadena Yolande Sandrine, NgoungourÉ Madeleine Chantal, Mballa Marguerite Francine, Mbolang Nguegan Lohik, Dimo Theophile, Kamtchouing Pierre Pages 63-71
    Introduction
    Nymphea lotus Linn (N. lotus) flowers are used empirically for the treatment of male sexual disorders in Cameroon west region. This study was aimed to evaluate the effects of the N. lotus on some parameters of male fertility in adult albino male rats.
    Methods
    twenty four male rats were divided in 4 groups (n=6 each) and subjected to the following treatment: distilled water as vehicle control (10 ml/kg), testosterone as reference drug (5 mg/kg) and N. lotus flowers aqueous extract at the doses of 75 (NL75) and 150 mg/kg (NL150). Distilled water and aqueous extract of the plant were given once daily whereas testosterone was injected intramuscularly once a week. Treatment lasted for 55 days. Index of libido, sperm count, motility and viability were assessed. Relative weight and histology of some androgens dependent organs were analyzed.
    Results
    Our results showed the treatment with NL75 during 55 days, increased markedly the index of libido (83.33%) in animals compared to control (50%). Both N. lotus treated groups showed a significant elevation (P
    Conclusion
    From these findings, it was concluded that N. lotus flowers have androgenic and reproductive properties justifying its empirical uses.
    Keywords: Plants, Androgens, Testis, Fertility, Male rats
  • Irfan Ahmed Sheikh, Muhammad Mubashshir, Safia Sumoona, Mohd Ovais Pages 72-79
    Introduction
    Effects of melatonin (MT) were comparatively examined on melanophores of isolated skin in adults and tadpole’s tailfin of a frog Rana cyanophlyctis. MT is generally considered as a potent melanophores aggregating hormone besides regulating the sleep wake cycle in vertebrates.
    Methods
    Melanophore size index (MSI) was chosen as a recording parameter of the responses. Concentration-response curve was obtained by application of MT to the frog skin. Against this MT, antagonists were employed to observe their blocking effects on aggregatory responses of frog melanophores.
    Results
    MT has induced aggregation in a wide dose-range on spotted and non-spotted regions in adults as well as in the tailfin of tadpoles. MT induced aggregation was somewhat independent to the applied concentrations of MT and beyond the dose 4.31 × 10-8 M of MT, aggregation of melanophores was decreased. Phenomenons of auto-desensitization and auto-antagonism have been observed. For tadpoles, the sensitivity to MT was higher than that of the adult skin melanophores as evident with the lowest threshold dose of MT to induce a discernible response. MT induced aggregatory responses were effectively inhibited by the specific MT antagonists luzindole and K-185 and also by the Ca channel blocker verapamil. Seasonal variation in inhibition of MT receptors by K-185 is being reported in this species.
    Conclusion
    Tadpole melanophores of Rana cyanophlyctis were more sensitive towards MT aggregation than their adult counterparts. Seasonal variations and auto-desensitization are all expressed through the specific MT1, MT2 receptors and Ca channels.
    Keywords: Autoantagonism, Autodesensitization, Melanophores, Melanosomes, Melatonin, Tadpoles
  • Zahra Abbasi, Gholamali Jelodar, Saeed Nazifi Pages 80-86
    Introduction
    Walnut leaf contains large amounts of antioxidants, phenolic compounds and flavonoids and the beneficial effect of these compounds in the treatment of diabetes has been shown. This study investigated the effect of cyclohexane and ethanol extract of walnut leaf on activity of sorbitol dehydrogenase (SDH) enzyme.
    Methods
    Fifty- six adult male Sprague-Dawley rats were divided into seven groups and treated for 30 days as follows: control and diabetic control (received sesame oil as vehicle), control cyclohexane & control ethanol (received 250 mg/kg body weight of cyclohexane and ethanol extracts respectively), diabetic cyclohexane 250 (received 250 mg/kg cyclohexane extract), and diabetic ethanol 150 & diabetic ethanol 250 (received 150 and 250 mg/kg ethanol extract respectively). Diabetes was induced by single injection of streptozotocin (60 mg/kg, ip). Body weight and blood glucose were recorded weekly and in the last day of treatment animals were sacrificed by whole blood collection directly from the heart. Activity of SDH was measured in the serum by ELISA method.
    Results
    Oral administration of cyclohexane extract of walnut leaf at a dose of 250 mg/kg in the diabetic group improved blood glucose significantly compared to other diabetic groups. Administration of both extracts reduced activity of SDH compared to diabetic control group significantly. There was no significant difference of body weight between treatment groups and diabetic control group at the end of the treatment period.
    Conclusion
    Cyclohexane extract of walnut leaf decreased blood glucose significantly, while both extracts reduced activity of SDH significantly in diabetic animals.
    Keywords: Diabetes mellitus, Sorbitol dehydrogenase, Extracts of walnut leaf