RESUMEN

BACKGROUND: Alzheimer's disease (AD) is linked to the accumulation of Aß, increased tau hyperphosphorylation, persistent neuroinflammation, and a decline in neurotrophic factors, neurogenesis, and synaptic plasticity. Oxytocin (OT) has a significant impact on memory and learning. We examined the influence of intranasal (IN) OT on synaptic plasticity, neurogenesis, histone acetylation, and spatial and cognitive memories in rats. METHODS: Aß25-35 (5 µg/2.5 µl) was administered bilaterally in the CA1 of male Wistar rats for four consecutive days. After seven days of recovery, OT (2 µg/µl, 10 µl in each nostril) was administered IN for seven consecutive days. Working, spatial, and cognitive memories, and gene expression of neurogenesis- and synaptic plasticity-involved factors were measured in the hippocampus. Histone acetylation (H3K9 and H4K8) was also measured using western blotting. RESULTS: IN administration of OT significantly improved working and spatial memory impairment induced by Aß and increased the factors involved in synaptic plasticity (MeCP2, REST, synaptophysin, and BDNF) and neurogenesis (Ki67 and DCX). We also found an enhancement in the levels of H3K9ac and H4K8ac following OT administration. CONCLUSION: These findings indicated that IN OT could improve hippocampus-related behaviors by increasing synaptic plasticity, stimulating neurogenesis, and chromatin plasticity.

RESUMEN

Interferon beta (IFNß) is a member of the type-1 interferon family and has various immunomodulatory functions in neuropathological conditions. Although the level of IFNß is low under healthy conditions, it is increased during inflammatory processes to protect the central nervous system (CNS). In particular, microglia and astrocytes are the main sources of IFNß upon inflammatory insult in the CNS. The protective effects of IFNß are well characterized in reducing the progression of multiple sclerosis (MS); however, little is understood about its effects in other neurological/neurodegenerative diseases. In this review, different types of IFNs and their signaling pathways will be described. Then we will focus on the potential role and therapeutic effect of IFNß in several CNS-related diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, stroke, spinal cord injury, prion disease and spinocerebellar ataxia 7.

Asunto(s)

Interferón beta , Humanos , Animales , Interferón beta/uso terapéutico , Interferón beta/metabolismo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/metabolismo , Transducción de Señal/efectos de los fármacos

RESUMEN

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive decline. Yttrium oxide nanoparticles (Y2O3NPs) have recently attracted much attention for their potential anti-inflammatory and antioxidant properties. However, the effects of Y2O3NPs in animal models of AD are less studied. This study aimed to investigate the potential therapeutic effects of Y2O3NPs in streptozotocin (STZ)-treated rats, a reliable animal model of AD, with special emphasis on cognitive function, neuroinflammation, and mitochondrial biogenesis in the hippocampus. Male Wistar rats were stereotaxically injected with STZ (3 mg/kg, 3 µl/ventricle). Three weeks after STZ injection, cognitive function was assessed using the Morris water maze, elevated plus maze, and passive avoidance tasks. Intraperitoneal treatment with Y2O3NPs (0.1, 0.3, or 0.5 mg/kg) was started 24 h after the STZ injection and continued for 21 days. The mRNA and protein levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) and components involved in mitochondrial biogenesis (PGC-1α, NRF-1, and TFAM) were measured in the hippocampus. The results indicated that STZ induced cognitive impairment and led to neuroinflammation and mitochondrial biogenesis impairment in the hippocampus of rats. Interestingly, treatment with Y2O3NPs effectively reduced STZ-induced cognitive deficits in a dose-dependent manner, possibly by attenuating neuroinflammation and mitochondrial biogenesis impairment. These findings suggest that Y2O3NPs can be considered as a promising therapeutic agent for treating or ameliorating the neuropathological effects associated with AD.

Asunto(s)

Disfunción Cognitiva , Hipocampo , Nanopartículas , Biogénesis de Organelos , Ratas Wistar , Estreptozocina , Itrio , Animales , Masculino , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Estreptozocina/toxicidad , Nanopartículas/administración & dosificación , Ratas , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Itrio/farmacología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/inducido químicamente , Modelos Animales de Enfermedad

RESUMEN

Methamphetamine (MA) induces neurocognitive effects via several mechanisms. In the present study, we investigated the alteration of thyroid hormone receptor's expression in the context of MA-induced memory impairment and explored the protective effects of exogenous thyroid hormones (THs). Male wistar rats, received increasing regimen of MA (1-10 mg/kg, intraperitoneal, twice a day for 10 days), were treated with T3 (40 µg/rat/day; intranasal, 2.5 µl/nostril) or T4 (20 µg/kg/day; intraperitoneal) for 7 days after MA cessation. All rats were subjected to novel object recognition memory test and then the mRNA levels of TH nuclear receptors (TRα1 and TRß1) and seladin-1, an anti-apoptotic factor, and the protein level of TH cell surface receptor (integrin αvß3) were measured in the hippocampus of rats. Our results showed that MA-induced memory impairment is concomitant with decreased level of TRα1 mRNA. T3 or T4 treatment significantly alleviated MA-induced memory impairment, but had no significant effect on the mRNA levels of TH nuclear receptors. However, T4 treatment significantly increased the protein level of cell surface receptor (αv subunit) in MA-treated rats. These findings suggest that MA neurocognitive effects can be associated with impaired TH signaling in the brain and introduce this pathway as a promising therapeutic approach against MA-induced memory impairment.

Asunto(s)

Metanfetamina , Animales , Masculino , Trastornos de la Memoria/inducido químicamente , Metanfetamina/toxicidad , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores de Hormona Tiroidea/genética , Hormonas Tiroideas

RESUMEN

Here, we introduced a patient with Mn-induced parkinsonism who was responsive to intranasal insulin, and his parkinsonism and dystonia responded to this treatment.

RESUMEN

INTRODUCTION: Midbrain dopaminergic neurons are involved in various brain functions, including motor behavior, reinforcement, motivation, learning, and cognition. Primary dopaminergic neurons and also several lines of these cells are extensively used in cell culture studies. Primary dopaminergic neurons prepared from rodents have been cultured in both DMEM/F12 and neurobasal mediums in several studies. However, there is no document reporting the comparison of these two mediums. So in this study, we evaluated the neurons and astroglial cells in primary midbrain neurons from rat embryos cultured in DMEM/F12 and neurobasal mediums. METHODS: Primary mesencephalon cells were prepared from the E14.5 rat embryo. Then they were seeded in two different mediums (Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 [DMEM/F12] and neurobasal). On day 3 and day 5, half of the medium was replaced with a fresh medium. On day 7, ß3-tubulin-, GFAP (Glial fibrillary acidic protein)- and Tyrosine Hydroxylase TH-positive cells were characterized as neurons, astrocytes, and dopaminergic neurons, respectively, using immunohistochemistry. Furthermore, the morphology of the cells in both mediums was observed under light microscopy on days 1, 3, and 5. RESULTS: The cells cultured in both mediums were similar under light microscopy regarding the cell number, but in a neurobasal medium, the cells have aggregated and formed clustering structures. Although GFAP-immunoreactive cells were lower in neurobasal compared to DMEM/F12, the number of ß3-tubulin- and TH-positive cells in both cultures was the same. CONCLUSION: This study's findings demonstrated that primary midbrain cells from the E14.5 rat embryo could grow in both DMEM/F12 and neurobasal mediums. Therefore, considering the high price of a neurobasal medium, it can be replaced with DMEM/F12 for culturing primary dopaminergic neurons.

RESUMEN

Adult neurogenesis in the hippocampal dentate gyrus plays a critical role in learning and memory. Projections originating from entorhinal cortex, known as the perforant pathway, provide the main input to the dentate gyrus and promote neurogenesis. However, neuromodulators and molecular changes mediating neurogenic effects of this pathway are not yet fully understood. Here, by means of an optogenetic approach, we investigated neurogenesis and synaptic plasticity in the hippocampus of adult rats induced by stimulation of the perforant pathway. The lentiviruses carrying hChR2 (H134R)-mCherry gene under the control of the CaMKII promoter were injected into the medial entorhinal cortex region of adult rats. After 21 days, the entorhinal cortex region was exposed to the blue laser (473 nm) for five consecutive days (30 min/day). The expression of synaptic plasticity and neurogenesis markers in the hippocampus were evaluated using molecular and histological approaches. In parallel, the changes in the gene expression of insulin and its signaling pathway, trophic factors, and components of mitochondrial biogenesis were assessed. Our results showed that optogenetic stimulation of the entorhinal cortex promotes hippocampal neurogenesis and synaptic plasticity concomitant with the increased levels of insulin mRNA and its signaling markers, neurotrophic factors, and activation of mitochondrial biogenesis. These findings suggest that effects of perforant pathway stimulation on the hippocampus, at least in part, are mediated by insulin increase in the dentate gyrus and subsequently activation of its downstream signaling pathway.

Asunto(s)

Corteza Entorrinal/fisiología , Hipocampo/fisiología , Neurogénesis , Optogenética , Vía Perforante/fisiología , Transducción de Señal , Animales , Giro Dentado/fisiología , Inmunohistoquímica , Insulina/metabolismo , Lentivirus , Masculino , Plasticidad Neuronal , Ratas , Ratas Wistar

RESUMEN

AIMS: Experimental and clinical evidences demonstrate that common dysregulated pathways are involved in Parkinson's disease (PD) and type 2 diabetes. Recently, insulin treatment through intranasal (IN) approach has gained attention in PD, although the underlying mechanism of its potential therapeutic effects is still unclear. In this study, we investigated the effects of insulin treatment in a rat model of PD with emphasis on mitochondrial function indices in striatum. METHODS: Rats were treated with a daily low dose (4IU/day) of IN insulin, starting 72 h after 6-OHDA-induced lesion and continued for 14 days. Motor performance, dopaminergic cell survival, mitochondrial dehydrogenases activity, mitochondrial swelling, mitochondria permeability transition pore (mPTP), mitochondrial membrane potential (Δψm ), reactive oxygen species (ROS) formation, and glutathione (GSH) content in mitochondria, mitochondrial adenosine triphosphate (ATP), and the gene expression of PGC-1α, TFAM, Drp-1, GFAP, and Iba-1 were assessed. RESULTS: Intranasal insulin significantly reduces 6-OHDA-induced motor dysfunction and dopaminergic cell death. In parallel, it improves mitochondrial function indices and modulates mitochondria biogenesis and fission as well as activation of astrocytes and microglia. CONCLUSION: Considering the prominent role of mitochondrial dysfunction in PD pathology, IN insulin as a disease-modifying therapy for PD should be considered for extensive research.

Asunto(s)

Insulina/administración & dosificación , Mitocondrias/efectos de los fármacos , Trastornos Motores/tratamiento farmacológico , Oxidopamina/toxicidad , Trastornos Parkinsonianos/tratamiento farmacológico , Administración Intranasal , Animales , Humanos , Masculino , Mitocondrias/fisiología , Trastornos Motores/inducido químicamente , Trastornos Motores/fisiopatología , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/fisiopatología , Ratas , Ratas Wistar , Rotación

RESUMEN

Tramadol, a weak agonist of mu-opioid receptors, causes seizure via several mechanisms. Preconditioning has been purposed to reduce the epileptic seizures in animal models of epilepsy. The preconditioning effect of tramadol on seizure is not studied yet. This study was designed to evaluate the preconditioning effect of ultra-low dose of tramadol on the seizures induced by tramadol at high dose. Furthermore, regarding the critical role of glutamate signaling in the pathogenesis of epilepsy, the effect of preconditioning on some glutamate signaling elements was also examined. Male Wistar rats received tramadol (2 mg/kg, i.p) or normal saline (1 mL/kg, i.p) in preconditioning and control groups, respectively. After 4 days, the challenging tramadol dose (150 mg/kg) was injected to all rats. Epileptic behaviors were recorded during 50 min. The expression of Norbin (as a regulator of metabotropic glutamate receptor 5), Calponin3 (as a regulator of excitatory synaptic markers), NR1 (NMDA receptor subunit 1) and GluR1 (AMPA receptor subunit 1) was measured in hippocampus, prefrontal cortex (PFC) and amygdala. Preconditioning decreased the number and duration of tremors and tonic-clonic seizures. Norbin, Calponin3, NR1 and GluR1 expression were decreased in hippocampus, and preconditioning had no effect on them. In contrast, it increased Norbin expression in PFC and amygdala, and attenuated NR1 and GluR1 upregulation following tramadol at high dose. These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation.

Asunto(s)

Analgésicos Opioides/administración & dosificación , Anticonvulsivantes/administración & dosificación , Encéfalo/efectos de los fármacos , Receptores AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Convulsiones/prevención & control , Tramadol/administración & dosificación , Analgésicos Opioides/toxicidad , Animales , Anticonvulsivantes/toxicidad , Encéfalo/metabolismo , Encéfalo/fisiopatología , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Masculino , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Neuropéptidos/genética , Neuropéptidos/metabolismo , Ratas Wistar , Receptores AMPA/genética , Receptores de N-Metil-D-Aspartato/genética , Convulsiones/inducido químicamente , Convulsiones/metabolismo , Convulsiones/fisiopatología , Índice de Severidad de la Enfermedad , Tramadol/toxicidad , Calponinas

RESUMEN

Epidermal neural crest stem cells (EPI-NCSCs) are propitious candidates for cell replacement therapy and supplying neurotrophic factors in the neurological disorders. Considering the potential remyelinating and regenerative effects of fingolimod, in this study, we evaluated its effects on EPI-NCSCs viability and the expression of neurotrophic and oligodendrocyte differentiation factors. EPI-NCSCs, extracted from the bulge of rat hair follicles, were characterized and treated with fingolimod (0, 50, 100, 200, 400, 600, 1000, and 5000 nM). The cell viability was evaluated by MTT assay at 6, 24 and 72 h. The expression of neurotrophic and differentiation factors in the cells treated with 100 and 400 nM fingolimod were measured at 24 and 120 h. Fingolimod at 50-600 nM increased the cells viability after 6 h, with no change at the higher concentrations. The highest concentration (5000nM) induced toxicity at 24 and 72 h. NGF and GDNF genes expression were decreased at 120 h, but on the contrary, brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) were increased by both concentrations at both time points. Oligodendrocyte markers including platelet-derived growth factor receptor A (PDGFRα), neuron-glial antigen 2 (NG2) and growth associated protein 43 (GAP43) were elevated at 120 h, which was accompanied with reduce in stemness markers (Nestin and early growth response 1 (EGR1)). Fingolimod increased the expression of neurotrophic factors in EPI-NCSCs, and guided them to oligodendrocyte fate. Therefore, fingolimod in combination with EPI-NCSCs, can be considered as a promising approach for demyelinating neurological disorders.

Asunto(s)

Epidermis/metabolismo , Clorhidrato de Fingolimod/farmacología , Cresta Neural/metabolismo , Células-Madre Neurales/metabolismo , Oligodendroglía/efectos de los fármacos , Moduladores de los Receptores de fosfatos y esfingosina 1/farmacología , Animales , Biomarcadores , Supervivencia Celular/efectos de los fármacos , Enfermedades Desmielinizantes/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Epidermis/efectos de los fármacos , Folículo Piloso/efectos de los fármacos , Masculino , Factores de Crecimiento Nervioso/metabolismo , Cresta Neural/citología , Cresta Neural/efectos de los fármacos , Células-Madre Neurales/efectos de los fármacos , Oligodendroglía/metabolismo , Ratas , Ratas Wistar

RESUMEN

Spinal cord injury (SCI), a multifactorial disease, can lead to irreversible motor and sensory disabilities. Cell therapy in combination with pharmacological agents can be a promising approach to attenuate SCI damages. Epidermal neural crest stem cells (EPI-NCSCs) extracted from bulge hair follicle in adults are attractive candidates due to the possibility of autologous transplantation. This study evaluated the effect of EPI-NCSCs combined with astaxanthin (Ast), a potent antioxidant, on damages induced by SCI. Male rats were treated with Ast (0.2 mM) and EPI-NCSCs (106/10 µl PBS) alone and combined together after SCI contusion. Motor function was assessed by Basso, Beattie and Bresnahan (BBB) test on days 1, 3, 7, 14, 21, 28, 35 and 42 post-injury. Motor neurons number and myelin level were evaluated on days 14 and 42 using Nissl and Luxol Fast Blue staining. The gene expression of mitochondrial biogenesis involved factors (PGC1α, NRF1 and TFAM) was measured by qPCR. All treatments improved motor function, with the highest BBB score in Ast + Cell compared to Ast and Cell. Decreased motor neurons number and myelin level following SCI, were increased by Ast, Cell and Ast + Cell, but combination therapy significantly had a better effect. We observed reduction in PGC1α, NRF1, and TFAM expression in spinal tissue after SCI, and treatment with Cell and Ast + Cell significantly restored NRF1 and TFAM mRNA levels. These results suggested that Ast in combination with EPI-NCSCs has better effects on behavioral dysfunction, motor neuron loss and demyelination after SCI. These protective effects may be attributed to mitochondrial biogenesis activation.

Asunto(s)

Mitocondrias/metabolismo , Cresta Neural/citología , Células-Madre Neurales/trasplante , Traumatismos de la Médula Espinal/terapia , Animales , Células Cultivadas , Terapia Combinada , Modelos Animales de Enfermedad , Masculino , Mitocondrias/genética , Trastornos Motores/metabolismo , Vaina de Mielina/metabolismo , Células-Madre Neurales/citología , Factor Nuclear 1 de Respiración/genética , Biogénesis de Organelos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Ratas , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/fisiopatología , Factores de Transcripción/genética , Trasplante Autólogo , Regulación hacia Arriba , Xantófilas/administración & dosificación , Xantófilas/farmacología

RESUMEN

Methamphetamine (MA), neurotoxic drug of abuse, causes cell death in vitro and in vivo via several mechanisms such as mitochondrial dysfunction. In this study we evaluated the effect of MA on cell viability and mitochondrial biogenesis in primary midbrain culture. Primary mesencephalon cells prepared from E14.5 rat embryo were treated with 0.2-5 mM MA concentrations for 24, 48, and 72 h. Morphological changes of the cells were observed under light microscope. Cell viability and cell death following MA were assessed using MTT assay and immunocytochemistry. Gene expressions of mitochondrial biogenesis-involved factors (PGC1α, NRF1 and TFAM), and neuronal and glial markers were measured by qPCR. Low to moderate MA concentrations elevated cell viability in all time points, while higher concentrations and longer incubation times (48 and 72 h) decreased it. Sphered cell bodies and neurites degeneration were observed following exposure to high MA concentrations. MA at 5 mM concentration decreased the number of ß3-tubulin-, TH-, GFAP- and Iba1-positive cells, and their corresponding mRNA levels; however, 1 mM MA reduced α-synuclein mRNA. Unexpectedly, gene expression of PGC1α, NRF1 and TFAM was increased in response to 5 mM MA, with no changes following 1 mM MA. The results indicated that MA effect on cell viability occurs in a dose-dependent manner. While moderate concentrations increased cell viability, the higher ones reduced it and caused cell death. Mitochondrial biogenesis activation, as a compensatory mechanism, did not prevent neuronal and glial cell death following high MA concentration.

Asunto(s)

Mesencéfalo/efectos de los fármacos , Metanfetamina/farmacología , Mitocondrias/efectos de los fármacos , Neuronas/efectos de los fármacos , Animales , Muerte Celular/efectos de los fármacos , Femenino , Mesencéfalo/metabolismo , Mitocondrias/metabolismo , Neuritas/efectos de los fármacos , Neuritas/metabolismo , Neuronas/metabolismo , Síndromes de Neurotoxicidad/tratamiento farmacológico , Biogénesis de Organelos , Ratas Wistar , alfa-Sinucleína/efectos de los fármacos , alfa-Sinucleína/metabolismo

RESUMEN

Methamphetamine (MA), a highly abused psychostimulant, exerts neurotoxic effects on the dopaminergic system via several neurotoxicity mechanisms in the long-term administration. Since the effect of MA on the signaling insulin pathway is less studied, the current study was designed to evaluate the effect of escalating an MA regimen on different insulin signaling elements in substantia nigra (SN) and striatum of a rat. Increasing MA doses (1-14 mg/kg) were administrated intraperitoneally twice a day for 14 days in rats. In the control group, normal saline was injected in the same volume. On days 1, 14, 28, and 60 after MA discontinuation, molecular assessments were performed. Insulin receptor (IR) and insulin receptor substrate (IRS) 1 and 2 gene expression were evaluated using real-time polymerase chain reaction, and protein levels of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), phospho-PI3K, Akt, phospho-Akt, glycogen synthase kinase 3ß (GSK3ß), and phospho-GSK3ß were measured by the Western blot analysis in SN and striatum. Messenger RNA levels of IR and insulin receptor substrate 2 were increased in SN, 1 day after the last injection. Although no changes were observed in PI3K, phospho-PI3K, Akt, phospho-Akt, and GSK3ß levels, increase in the level of inactive form of GSK3ß (phosphorylated on serine 9) was indicated in SN on day 28. In striatum, decreases in IR and phospho-Akt were demonstrated, without any change in other elements. Repeated escalating regimen of MA activated the insulin signaling pathway and inhibited GSK3ß activity in SN. This response, which did not occur in striatum, may act as an adaptive mechanism to prevent MA-induced neurotoxicity in dopaminergic cell bodies.

Asunto(s)

Estimulantes del Sistema Nervioso Central/farmacología , Glucógeno Sintasa Quinasa 3 beta/antagonistas & inhibidores , Insulina/metabolismo , Metanfetamina/farmacología , Transducción de Señal/efectos de los fármacos , Sustancia Negra/metabolismo , Análisis de Varianza , Animales , Cuerpo Estriado/metabolismo , Relación Dosis-Respuesta a Droga , Expresión Génica , Inyecciones Intraperitoneales , Proteínas Sustrato del Receptor de Insulina/genética , Masculino , Metanfetamina/administración & dosificación , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor de Insulina/genética

RESUMEN

Methamphetamine (MA), a highly addictive psychostimulant, produces long-lasting neurotoxic effects well proven in nigrostriatal dopaminergic neurons. Considering the similarities between pathological profile of MA neurotoxicity and Parkinson's disease (PD), some reports show that previous MA abusers will be at greater risk of PD-like motor deficits. To answer the question if repeated MA exposure causes parkinsonian-like behavior in rats, we used three regimens of MA administration and assessed the motor performance parameters immediately and over a long period after MA discontinuation. Male Wistar rats in two experimental groups were treated with escalating paradigms consisting of twice daily intraperitoneal injection of either 1-7 mg/kg or 1-14 mg/kg of MA over 14 days. The third group received twice-daily doses of 15 mg/kg of MA every other day for total number of 7 days. At the 1st, 7th, 14th, 21st, 28th, and 60th days after last injections, motor activities were evaluated using narrow beam, pole, and rotarod tests. Locomotor activity was also evaluated using open field test. Repeated-measures ANOVA indicated that over the two months period following MA exposure, drug-treated rats perform beam, pole, and rotarod tests equally well as their corresponding vehicle-treated controls. Comparison of the locomotor activity didn't show significant differences between groups. These data indicated that MA at these regimens does not cause PD-related motor deficits in rats. Since MA doses, exposure duration, and dosing intervals have been shown to affect MA-induced dopaminergic toxicity, it can be concluded that none of these regimens; are strong enough to produce measurable behavioral motor deficits in rat.

RESUMEN

AIMS AND OBJECTIVES: Root canal preparation and obturation are of great importance in endodontics. Its purpose is to eliminate pulpal and periradicular disease. The aim of this study was to compare coronal bacterial microleakage in prepared root canals using Neoniti A1 and Reciproc files that obturated with lateral compaction, single cone gutta-percha, and hybrid (tapered cone/lateral compaction) methods. MATERIALS AND METHODS: In this ex vivo study, a total of 110 single-rooted mandibular first premolars were choose and randomly divided into two study groups A and B (each 45) that one group was prepared with Reciproc and another with Neoniti A1 and negative and positive control groups (each 10). Each group divided into three subgroups of 15 each and obturated using a single cone, lateral compaction, and hybrid (tapered cone/lateral compaction) techniques. For evaluation of coronal leakage, "two-chamber setup" was used. The solution of enterococcus faecalis culture was injected in the upper chamber and incubated. If the bacteria pass through the canal and obturation materials, the lower chamber becomes turbid. TSB medium in the lower chamber (apex) were investigated every day in terms of occurrence of turbidity, and the duration of occurrence of leakage was recorded. The data were analyzed using Chi-square test. RESULTS: Data analysis showed that in each group the difference in percentages between subgroups was statistically significant (P = 0.003). So that the highest and the lowest amount of leakage in both groups were related to lateral compaction and hybrid techniques, respectively. CONCLUSION: Under the conditions of this study, independent of the instrument used for canal preparation, hybrid method and then single-cone technique, however, were more effective in the prevention of coronal leakage than lateral condensation technique.

RESUMEN

Methamphetamine (MA) produces long-lasting deficits in dopaminergic neurons in the long-term use via several neurotoxic mechanisms. The effects of MA on mitochondrial biogenesis is less studied currently. So, we evaluated the effects of repeated escalating MA regimen on transcriptional factors involved in mitochondrial biogenesis and glial-derived neurotrophic factor (GDNF) expression in substantia nigra (SN) and striatum of rat. In male Wistar rats, increasing doses of MA (1-14 mg/kg) were administrated twice a day for 14 days. At the 1st, 14th, 28th, and 60th days after MA discontinuation, we measured the PGC1α, TFAM and NRF1 mRNA levels, indicator of mitochondrial biogenesis, and GDNF expression in SN and striatum. Furthermore, we evaluated the glial fibrillary acidic protein (GFAP) and Iba1 mRNA levels, and the levels of tyrosine hydroxylase (TH) and α-synuclein (α-syn) using immunohistochemistry and real-time polymerase chain reaction (PCR). We detected increments in PGC1α and TFAM mRNA levels in SN, but not striatum, and elevations in GDNF levels in SN immediately after MA discontinuation. We also observed increases in GFAP and Iba1 mRNA levels in SN on day 1 and increases in Iba1 mRNA on days 1 and 14 in striatum. Data analysis revealed that the number of TH+ cells in the SN did not reduce in any time points, though TH mRNA levels was increased on day 1 after MA discontinuation in SN. These data show that repeated escalating MA induces several compensatory mechanisms, such as mitochondrial biogenesis and elevation in GDNF in SN. These mechanisms can reverse MA-induced neuroinflammation and prevent TH-immunoreactivity reduction in nigrostriatal pathway. J. Cell. Biochem. 118: 1369-1378, 2017. © 2016 Wiley Periodicals, Inc.

Asunto(s)

Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Metanfetamina/administración & dosificación , Mitocondrias/efectos de los fármacos , Sustancia Negra/efectos de los fármacos , Factores de Transcripción/genética , Animales , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Masculino , Metanfetamina/farmacología , Mitocondrias/genética , Factor Nuclear 1 de Respiración/genética , Factor Nuclear 1 de Respiración/metabolismo , Biogénesis de Organelos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Ratas , Ratas Wistar , Sustancia Negra/metabolismo , Factores de Transcripción/metabolismo , Tirosina 3-Monooxigenasa/genética , Tirosina 3-Monooxigenasa/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo