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1.
Indian J Otolaryngol Head Neck Surg ; 75(Suppl 1): 6-15, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37206728

RESUMEN

Tinnitus is a symptom of various disorders that affects the quality of life of millions people. Given the significance of the access to an objective and non-invasive method for tinnitus detection, in this study the auditory brainstem response (ABR) electrophysiological test was used to diagnose salicylate-induced tinnitus, in parallel with common behavioral tests. Wistar rats were divided into saline (n = 7), and salicylate (n = 7) groups for behavioral tests, and salicylate group (n = 5) for the ABR test. The rats were evaluated by pre-pulse inhibition (PPI), gap pre-pulse inhibition of the acoustic startle (GPIAS), and ABR tests, at baseline, 14 and 62 h after salicylate (350 mg/kg) or vehicle injection. The mean percentage of GPIAS test was significantly reduced following salicylate administration, which confirms the induction of tinnitus. The ABR test results showed an increase in the hearing threshold at click and 8, 12, and 16 kHz tones. Moreover, a decline was observed in the latency ratio of II-I waves in all tone burst frequencies with the highest variation in 12 and 16 kHz as well as a decrement in the latency ratio of III-I and IV-I only in 12 and 16 kHz. ABR test is able to evaluate the salicylate induced tinnitus pitch and confirm the results of behavioral tinnitus tests. GPIAS reflexive response is dependent on brainstem circuits and the auditory cortex while, ABR test can demonstrate the function of the auditory brainstem in more details, and therefore, a combination of these two tests can offer a more accurate tinnitus evaluation.

2.
Brain Sci ; 13(3)2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36979223

RESUMEN

Humans and animals frequently make an endeavor-based choice based on assessing reinforcement value and response costs. The cortical-limbic-striatal pathway mediates endeavor-based choice behavior, including the nucleus accumbens (NAc) and the anterior cingulate cortex (ACC). Furthermore, cannabinoid agonists demonstratively impairs decision-making processes. In this study, neural synchronization and functional connectivity between the NAc and ACC while endeavor-related decision-making and reaching reward were evaluated. The effect of exogenous cannabinoids on this synchronization was then assessed. A T-maze decision-making task with a differential expense (low vs. high endeavor) and remuneration (low vs. high remuneration) was performed and local field potentials (LFP) from the ACC and NAc were registered simultaneously. Results showed functional connectivity during endeavor-related decision-making while the animals chose the high endeavor/high remuneration in both regions' delta/beta (1-4 and 13-30 Hertz) frequency bands. Furthermore, functional connectivity existed between both areas in delta/theta (1-4 and 4-12) frequencies while reaching a remuneration. However, neural simultaneity was not observed while the animals received cannabinoid agonists, making a decision and reaching remuneration. The obtained results demonstrated that functional connectivity and neural simultaneity between the NAc and ACC in delta/beta and delta/theta frequencies have a role in endeavor-related decision-making and reaching remuneration, respectively. The effect of exogenous cannabinoids on decision-making impairment is relevant to changes in the ACC and NAC brain wave frequencies.

3.
Mar Drugs ; 21(3)2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36976217

RESUMEN

Nowadays, major attention is being paid to curing different types of cancers and is focused on natural resources, including oceans and marine environments. Jellyfish are marine animals with the ability to utilize their venom in order to both feed and defend. Prior studies have displayed the anticancer capabilities of various jellyfish. Hence, we examined the anticancer features of the venom of Cassiopea andromeda and Catostylus mosaicus in an in vitro situation against the human pulmonary adenocarcinoma (A549) cancer cell line. The MTT assay demonstrated that both mentioned venoms have anti-tumoral ability in a dose-dependent manner. Western blot analysis proved that both venoms can increase some pro-apoptotic factors and reduce some anti-apoptotic molecules that lead to the inducing of apoptosis in A549 cells. GC/MS analysis demonstrated some compounds with biological effects, including anti-inflammatory, antioxidant and anti-cancer activities. Molecular docking and molecular dynamic showed the best position of each biologically active component on the different death receptors, which are involved in the process of apoptosis in A549 cells. Ultimately, this study has proven that both venoms of C. andromeda and C. mosaicus have the capability to suppress A549 cells in an in vitro condition and they might be utilized in order to design and develop brand new anticancer agents in the near future.


Asunto(s)
Adenocarcinoma , Cnidarios , Venenos de Cnidarios , Neoplasias Pulmonares , Escifozoos , Animales , Humanos , Venenos de Cnidarios/farmacología , Venenos de Cnidarios/química , Células A549 , Simulación del Acoplamiento Molecular , Adenocarcinoma/tratamiento farmacológico , Apoptosis , Neoplasias Pulmonares/tratamiento farmacológico
4.
Basic Clin Neurosci ; 13(3): 407-420, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36457878

RESUMEN

Introduction: Introduction: Several studies have demonstrated that orexins may regulate different forms of affective and cognitive processes during wakefulness. The Orbitofrontal Cortex (OFC) and Anterior Cingulate Cortex (ACC), as an essential part of the Prefrontal Cortex (PFC), have a crucial role in cognitive processes such as reward and decision-making. They also have a high amount of orexin receptor type 1 (OX1Rs). Methods: In the present study, we inhibited OX1Rs in this area after a 10-min baseline recording to find out the role of OX1Rs in the OFC neuron's firing rate. Next, we inhibited the lateral hypothalamus (LH) as the primary source of orexinergic neurons. Afterward, using a single-unit recording technique in rats, we detected the effects of the lateral hypothalamus on the firing rate and activity pattern of the ACC or OFC neurons. Results: Data showed that the blockade of OX1Rs in the OFC could excite 8 and inhibit 1 neuron(s) out of 11. In addition, the blockade of OX1Rs in the ACC could excite 6 and inhibit 3 neurons out of 10. LH inactivation excited 5 out of 12 neurons and inhibited 6 in the ACC. It also excited 8 and inhibited 6 neurons out of 14 in the OFC. These data suggest that the blockade of OX1Rs excites 72% of the neurons, but LH inactivation had a stimulating effect on only 50% of neurons in two main subregions of the PFC. Conclusion: Accordingly, PFC neurons may receive the orexinergic inputs from the LH and indirectly from other sources. Highlights: Blockade of orexin receptors 1 in ACC alter neural activity in this region.Blockade of orexin receptors 1 in OFC alter neural activity in this region.Lateral hypothalamus inhibition increase neural activity of only 50% neurons in ACC and OFC. Plain Language Summary: The discovery of the neuropeptide orexin/hypocretin in 1998 and subsequent research during the past 20 years revealed an important role for the lateral hypothalamus (LH) in driving the reward pathway, sleep and awake circuits, decision making and psychotic disorders. But our knowledge towards the function of this neurotransmitter on neural activity in specific areas of the brain is limited. In this study we decided to clear the specific role of orexin receptors placed in the two crucial areas of medial prefrontal cortex (mPFC) and the orexin projections from LH on neural firing rates in those regions. In the present study, we investigated the following items by using an in vivo extracellular single-unit recording technique in rats and our data shown that the effect of blocking of orexin receptors1 in mPFC caused a different results than inhibition of the origin of orexin projection in LH as a source of it.

5.
Sci Rep ; 12(1): 19356, 2022 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-36369256

RESUMEN

Light and optical techniques are widely used for the diagnosis and treatment of neurological diseases as advanced methods. Understanding the optical properties of nervous tissue and nerve cells is vital. Using light sources in these methods raises significant challenges, such as finding the place of light transmission in nerve fibers that could be an appropriate substrate for neural signaling. The myelinated axons are a promising candidate for transmitting neural signals and light due to their waveguide structures. On the other hand, with the emergence of diseases such as multiple sclerosis and disorders within the production and transmission of nerve signals, because of the demyelination, understanding the properties of the myelinated axon as a waveguide is obtaining additional necessity. The present study aims to show that the myelinated axon's refractive index (RI) profile plays an essential role in transmitting the beams in it. According to the nerve fiber, RI profile and its similarity to depressed core fiber with lower RI of the core compared to the cladding, the behaviors of the nerve fiber based on anti-resonant reflecting optical waveguide structure are investigated by taking into account the realistic optical imperfections. Light launching to the myelin sheath and axon is shown by introducing the axon and myelin sheath as a waveguide in the presence of both axon and myelin with bends, myelin sheath variation, and node of Ranvier.


Asunto(s)
Vaina de Mielina , Fibras Nerviosas Mielínicas , Fibras Nerviosas Mielínicas/fisiología , Vaina de Mielina/fisiología , Axones/fisiología
6.
Artículo en Inglés | MEDLINE | ID: mdl-33964323

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
7.
Mater Sci Eng C Mater Biol Appl ; 117: 111328, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32919682

RESUMEN

The hippocampus, a critical cerebral region involved in learning and memory formation, is especially vulnerable to ischemic defect. Here, we developed an injectable electroactive hydrogel based on pluronic-chitosan/aniline-pentamer with proper conductivity around 10-4 S/cm to achieve the functional repair of the hippocampus following the ischemic defect. FTIR, DSC, and TGA measurements were performed to assess the chemical structure and thermal stability of the synthesized hydrogel. Aniline pentamer decreased the swelling capacity, degradation, and drug release rate. Further, contact angle, melting point, and gelation time of hydrogels were enhanced by addition of aniline oligomer. Moreover, it endowed the on-demand electro-responsive drug release. Injectability of hydrogel was evaluated by rheometry, exhibiting proper gelling time at the body temperature. The ionic/electrical conductivity and desired in vitro biocompatibility with PC12 cells were also achieved. Injection of VEGF-loaded electroactive hydrogel in the hippocampal ischemic animal model resulted in decreased infarction volume, improved hippocampal dependent learning, and memory performance. Taken all together, the results confirmed that fabricated injectable hydrogel would be a suitable candidate for ischemic defect treatment and can lead to new horizons to treat neurological disorders.


Asunto(s)
Quitosano , Hidrogeles , Inductores de la Angiogénesis , Compuestos de Anilina/farmacología , Animales , Quitosano/análogos & derivados , Hipocampo , Isquemia , Ratas
8.
J Chem Neuroanat ; 109: 101821, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32512152

RESUMEN

INTRODUCTION: Human dental pulp stem cells (hDPSCs), a promising source for autologous transplantation in regenerative medicine, have been shown to be able to differentiate into neural precursors. Optogenetics is considered as an advanced biological technique in neuroscience which is able to control the activity of genetically modified stem cells by light. The purpose of this study is to investigate the neurogenic differentiation of hDPSCs following optogenetic stimulation. METHODS: The hDPSCs were isolated by mechanical enzymatic digestion from an impacted third molar and cultured in DMEM/F12. The cells were infected with lentiviruses carrying CaMKIIa-hChR2 (H134R). Opsin-expressing hDPSCs were plated at the density of 5 × 104 cells/well in 6-well plates and optical stimulation was conducted with blue light (470 nm) pulsing at 15 Hz, 90 % Duty Cycle and 10 mW power for 10 s every 90 minutes, 6 times a day for 5 days. Two control groups including non-opsin-expressing hDPSCs and opsin-expressing hDPSCs with no optical stimulation were also included in the study. A day after last light stimulation, the viability of cells was analyzed by the MTT assay and the morphological changes were examined by phase contrast microscopy. The expression of Nestin, Microtubule-Associated protein 2 (MAP2) and Doublecortin (DCX) were examined by immunocytochemistry. RESULTS: Human DPSCs expressed the reporter gene, mCherry, 72 hours after lentiviral infection. The result of MTT assay revealed a significant more viability in optical stimulated opsin-expressing hDPSCs as compared with two control groups. Moreover, optical stimulation increased the expression of Nestin, Doublecortin and MAP2 along with morphological changes from spindle shape to neuron-like shape. CONCLUSION: Optogenetics stimulation through depolarizing the hDPSCs can increase the cells viability and/or proliferation and also promote the differentiation toward neuron-like cells.


Asunto(s)
Pulpa Dental/citología , Neurogénesis/fisiología , Optogenética , Células Madre/citología , Adolescente , Adulto , Proliferación Celular/fisiología , Humanos , Adulto Joven
9.
Neuromolecular Med ; 21(2): 132-142, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30784006

RESUMEN

Epigenetic agents, such as neonatal isolation during neurodevelopmental period of life, can change various regions of the brain. It may further induce psychological disorders such as autistic-like phenomena. This study indicated the role of chronic increased anterior cingulate cortex (ACC) output on alteration of caudate putamen (CPu) as a main behavior regulator region of the brain in adult maternal deprived (MD) rats. For making an animal model, neonates were isolated from their mothers in postnatal days (PND 1-10, 3 h/day). Subsequently, they bilaterally received pLenti-CaMKIIa-hChR2 (H134R)-mCherry-WPRE virus in ACC area via stereotaxic surgery in PND50. After 22 days, these regions were exposed to blue laser (473 nm) for six consecutive days (15 min/day). Then, behavioral deficits were tested and were compared with control group in the following day. Animals were immediately killed and their brains were prepared for tissue processing. Results showed that neonatal isolation induces autistic-like behaviors and leads to overexpression of NMDAR1 and Nox2-gp91phox proteins and elevation of catalase activity in the CPu regions of the adult offspring compared with control group. Chronic optogenetic stimulation of ACC neurons containing (ChR2+) led to significant reduction in the appearance of stereotypical behavior and alien-phobia in MD rats. The amount of NMDAR1 and Nox2-gp91phox expression and the catalase activity in CPu were reduced after this treatment. Therefore, autistic-like behavior seems to be related with elevation of NMDAR1 and Nox2-gp91phox protein levels that enhance the effect of glutamatergic projection on CPu regions. Optogenetic treatment also could ameliorate behavioral deficits by modulating these protein densities.


Asunto(s)
Trastorno Autístico , Núcleo Caudado , Giro del Cíngulo , Privación Materna , Optogenética , Putamen , Animales , Femenino , Masculino , Ratas , Animales Recién Nacidos , Trastorno Autístico/fisiopatología , Trastorno Autístico/terapia , Catalasa/biosíntesis , Catalasa/genética , Núcleo Caudado/fisiopatología , Modelos Animales de Enfermedad , Genes Reporteros , Vectores Genéticos/administración & dosificación , Giro del Cíngulo/fisiopatología , Proteínas Luminiscentes/análisis , Proteínas Luminiscentes/genética , Microinyecciones , NADPH Oxidasa 2/biosíntesis , NADPH Oxidasa 2/genética , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Fobia Social , Putamen/fisiopatología , Distribución Aleatoria , Receptores de N-Metil-D-Aspartato/biosíntesis , Receptores de N-Metil-D-Aspartato/genética , Conducta Social , Estrés Psicológico , Proteína Fluorescente Roja
10.
Tissue Cell ; 56: 90-97, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30736910

RESUMEN

Nowadays there are various models of spinal cord injury (SCI) that recreate mechanisms of human SCI. The ex vivo modeling of injury is a robust approach, confronts with less experimental and ethical challenges. Currently almost all ex vivo models are obtained either from embryonic or postnatal animals, which can hardly mimic features of human SCI. This study was designed to develop SCI in slice culture of adult rats. Here, the lumbar enlargement of an adult rat was sliced and cultured. After seven days in vitro, a weight was dropped to simulate the injury. The result showed that although the rate of cell death in first days of in vitro was high, it reduced after 7 days and dropping a weight at the time caused significant rate of cell death in slices. It was shown that injury can disturb histological features and neuronal integrity in the slices. Treating the injured slices with valproic acid resulted in a significant decrease of TNF-α and increase of BDNF expression. Collected data revealed obtained slices from adult rat were able to adjust to the culture environment after 7 days and dropping a weight at the time point could simulate the injury. Besides mimicking the disturbing features of human SCI, this model can response to VPA pharmacological treatment.


Asunto(s)
Técnicas de Cultivo de Órganos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Médula Espinal/crecimiento & desarrollo , Ácido Valproico/farmacología , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Neuronas/patología , Ratas , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/patología , Factor de Necrosis Tumoral alfa/genética
11.
Toxicol Res (Camb) ; 8(6): 953-963, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34055310

RESUMEN

Toxicity evaluations of micro- or nano-sized plastics in rodent species commonly employed for toxicity analyses based on which risk assessment for humans could be performed are still largely lacking. Given this knowledge gap, the present work was aimed at determining the potential impact of chronic exposure to polystyrene nanoplastics (PS NPs) on the thyroid endocrine status and biochemical stress in a rat model. Young adult male rats were orally administered with PS NPs (1, 3, 6 and 10 mg kg-1 day-1) for five weeks. Thyroid hormones (THs) l-thyroxine (T4), l-triiodothyronine (T3), l-free triiodothyronine (FT3), and l-free thyroxine (FT4) as well as thyroid stimulating hormone (TSH) serum levels of normal rats and those exposed to PS NPs were compared. Serum levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol, and creatinine, as well as glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) enzymes were also measured. Exposure to PS NPs suppressed the serum levels of T3 and circulating levels of THs, whereas TSH increased significantly. Though exposure to PS NPs did not affect the molar ratios of T3/T4, it induced a slight, but significant, increase in FT3/FT4. In addition, exposure to plastic nanoparticles showed signs of nephrotoxicity induction and kidney injury in exposed organisms as can be inferred from the significantly higher serum levels of creatinine in exposed groups. Our results provide clear evidence of an association between exposure to plastic NPs and thyroid endocrine disruption as well as metabolic deficit, and generate new leads for future research efforts.

12.
Brain Res Bull ; 144: 75-84, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30472148

RESUMEN

Deep brain stimulation (DBS) has been established as a therapeutically effective method to treat pharmacological resistant neurological disorders. The molecular and cellular mechanisms underlying the beneficial effects of DBS on the brain are not yet fully understood. Beside numerous suggested mechanisms, regulation of neurogenesis is an attractive mechanism through which DBS can affect the cognitive functions. Considering the high expression of insulin receptors in hippocampus and also impaired neurogenesis in diabetic brain, the present study aimed to examine the role of insulin receptor signaling in DBS induced neurogenesis. High frequency stimulation was applied on the entorhinal cortex of rats and then neurogenesis markers in the dentate gyrus region of the hippocampus were examined using molecular and histological methods in the sham, DBS and insulin receptor antagonist-treated groups. In parallel, the changes in insulin receptor signaling in the hippocampus and spatial learning and memory performance were also assessed. DBS promoted adult hippocampal neurogenesis and facilitated the spatial memory concomitant with changes in insulin receptor signaling parameters including IR, IRS2 and GSK3ß. Application of insulin receptor antagonist attenuated the DBS-induced neurogenesis. Our data emphasize that entorhinal cortex stimulation promotes adult hippocampal neurogenesis and facilitates spatial learning and memory at least partly through insulin receptors. Notably, GSK3ß inhibition can play a major role in the downstream of insulin receptor signaling in DBS induced neurogenesis.


Asunto(s)
Giro Dentado/metabolismo , Corteza Entorrinal/fisiología , Receptor de Insulina/metabolismo , Animales , Encéfalo/fisiología , Estimulación Encefálica Profunda/métodos , Corteza Entorrinal/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hipocampo/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Neurogénesis/fisiología , Ratas , Ratas Wistar , Transducción de Señal , Aprendizaje Espacial/fisiología , Memoria Espacial/fisiología
13.
J Pharmacol Toxicol Methods ; 94(Pt 1): 77-86, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29906509

RESUMEN

INTRODUCTION: The vulnerability of hippocampal formation to ischemic insult has been documented in both humans and animal models. Ischemic injury induction through photothrombosis is an invasive and reproducible model of ischemic stroke which provides the ability to induce ischemia selectively in any desired area. In this study, we describe a method to induce selective unilateral hippocampal ischemia in rat through modified photothrombotic model. METHODS: Male wistar rats (n = 66) were subjected to stereotaxic surgery to insert a guide cannula just above the ascending part of hippocampal fissure. After recovery femoral vein was cannulated and rats were mounted in stereotaxic frame to optical fiber insertion in guide cannula and illumination of hippocampal fissure for 25 min. Rose Bengal dye was slowly injected through femoral vein during the first two-minute of illumination. Twenty-four hours later, infarct volume and histological change were evaluated in rat hippocampus. Cognitive function was also evaluated 48 h after ischemia induction. RESULTS: This procedure caused significant neuronal necrosis and infarct formation in the right hemisphere hippocampus. The infarct size was consisted in different subjects and was paralleled to cognitive impairment. The mean volume of infarction was 6.5% which affected whole right hippocampus and caused significant cognitive impairment compared to sham group (P < 0.001). DISCUSSION: The method described in this study provides the ability of selective hippocampal ischemia induction and study of hippocampal injury consequences following ischemia or other neurodegenerative disease that affect hippocampus.


Asunto(s)
Isquemia Encefálica/fisiopatología , Hipocampo/fisiopatología , Animales , Disfunción Cognitiva/fisiopatología , Modelos Animales de Enfermedad , Masculino , Neuronas/fisiología , Estimulación Luminosa/métodos , Ratas , Ratas Wistar , Accidente Cerebrovascular/fisiopatología
14.
Behav Brain Res ; 347: 26-36, 2018 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-29501508

RESUMEN

Finding a neuroprotective strategy to rescue patients suffering from acute brain damage is of great interest. Monophosphoryl lipid A (MPL) is a derivative of lipopolysaccharide (LPS) that lacks many of the endotoxic properties of the parent molecule, and yet has similar protective effect. Here, we report the first evidence that MPL preconditioning, similar to LPS preconditioning, can induce neuroprotection against cerebral ischemia. MPL (0.5, 1, 5 µg/rat) was injected unilaterally into the left cerebral ventricle of male rats, and 48 h later, rats were subjected to ipsilateral selective hippocampal ischemia using a modified version of the photothrombotic method. The neuroprotective effects of MPL and LPS were evaluated by measuring infarct size and assessing cognitive function. The expression level of some inflammatory and anti-inflammatory cytokines involving in TLR4 signaling pathway was also measured. Cognitive impairment and infarct size were obvious in control group receiving normal saline intracerebroventricularly and then selective hippocampal ischemia, compared to the sham group. Immunologic preconditioning with MPL or LPS significantly reduced infarct size and improved cognitive function. Additionally, immunologic preconditioning resulted in inflammatory mediators, NF-κB and TNF-α, down-regulation but anti-inflammatory mediators, IRF3, IFN-ß, and TGF-ß, up-regulation. Our data showed that both MPL and LPS preconditioning may reprogram the TLR4 signaling pathway to produce a cytokine profile which eventually leads to neuroprotection against ischemia injury. MPL, unlike LPS, is safe and well tolerated in clinic, thus it could be considered as a new approach in prevention or even treatment of cerebral ischemic insult consequences.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Lípido A/análogos & derivados , Fármacos Neuroprotectores/farmacología , Animales , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Isquemia Encefálica/psicología , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Lateralidad Funcional , Hipocampo/metabolismo , Hipocampo/patología , Lípido A/farmacología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , FN-kappa B/metabolismo , Distribución Aleatoria , Ratas Wistar , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
15.
Behav Brain Res ; 335: 19-25, 2017 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-28797601

RESUMEN

The basolateral amygdala (BLA) plays a critical role in the neural circuitry of stress and mediates the effects of stress on memory related processes. Moreover, this area has an important role in drug-seeking and relapse of approach behavior to drug-associated cues. Therefore, in the present study, we aimed to investigate the effects of acute and subchronic stress in saline- and/or morphine-treated rats in conditioned place preference paradigm on the neural activity in the BLA. Male Wistar rats were divided into two saline- and morphine-treated supergroups. Each supergroup contained control, acute stress (AS) and subchronic stress (SS) groups. In all of the groups, conditioned place preference paradigm was done and thereinafter the spontaneous firing activity was recorded by in vivo single unit recording for 20min. Results showed that in saline-and/or morphine-treated animals, both AS and SS increased neural activity of projection neurons and this increase in morphine-treated animals was more considerable than that of saline-treated animals. Besides, firing rate of interneurons in both supergroups decreased during AS and SS. Decrease of interneurons activity after application of SS in morphine-treated animals was more than that of saline-treated animals. These finding revealed that both of AS and SS increased firing rate of projection neurons but decreased neural activity of interneurons in the BLA. However, effect of AS and SS on the firing rate of BLA neurons in morphine-treated animals was more remarkable than that of saline-treated animals.


Asunto(s)
Complejo Nuclear Basolateral/efectos de los fármacos , Complejo Nuclear Basolateral/fisiología , Morfina/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Ondas Encefálicas/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Morfina/metabolismo , Narcóticos/farmacología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Ratas , Ratas Wistar
16.
Int J Biol Macromol ; 72: 806-11, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25251241

RESUMEN

G-quadruplexes are supramolecular structures of G-rich nucleic acid, formed by non-canonical base pairing in the presence of specific environmental inducers. These structures have been vastly considered in diagnostic and therapeutic applications. However, detailed information on structure, optical properties and thermal stability of G-quadruplex potent oligonucleotides is scarce. Herein, optical properties and thermodynamic stability of AS1411 quadruplex is reported for various concentrations of potassium and lead ions. Circular dichroism showed that AS1411 ss-DNA folds into parallel conformation in the presence of metal ions and molecular crowding condition. UV-vis spectroscopy indicated formation of quadruplex and fluorescent spectroscopy revealed intercalation of PicoGreen in its structure, with enhancement of emission intensity upon increment of metal ion concentration. This investigation also proposes high-throughput and reliable analysis of AS1411 quadruplex's thermal stability by real-time PCR technique, which can be further applied for other quadruplex structures.


Asunto(s)
ADN/química , G-Cuádruplex , Dicroismo Circular , ADN/metabolismo , ADN Catalítico/química , Oligonucleótidos/química , Termodinámica
17.
J Photochem Photobiol B ; 135: 55-64, 2014 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-24813110

RESUMEN

Silver nanoparticles (SNPs) exhibit antibacterial properties via bacterial inactivation and growth inhibition but the mechanism is not yet completely understood. In this study a label free and rapid detection method for study of antimicrobial activity of the SNP against Escherichia coli (E. coli K-12) is investigated using a nonadiabtic tapered fiber optic (NATOF) biosensor. The results show that SNPs interact with bacteria either by anchoring to or penetrating into the bacterial cell layer. These mechanism changes the refractive index (RI) of the tapered region, which in turn lead to the changes in the optical characteristics of the tapered fiber and output signals. With similar conditions for bacteria, the inhibition rate of the E. coli growth was measured by colony counting method as an experimental control and the results were compared with those obtained from the fiber sensor measurements. For SNP concentrations ranging from 0 to 50 µg ml(-1) the inhibition rates of the E. coli growth were measured to be from 1.27 h(-1) to -0.69 h(-1) and from -3.00×10(-3) h(-1) to -1.98×10(-2) h(-1) for colony counting and optical fiber biosensor, respectively. The results demonstrate the potential of the proposed NATOF biosensor as a label free and rapid sensing platform for understanding the mechanism of antibacterial effects of SNPs.


Asunto(s)
Antibacterianos/farmacología , Técnicas Biosensibles/instrumentación , Escherichia coli K12/efectos de los fármacos , Nanopartículas del Metal , Fibras Ópticas , Plata/química , Plata/farmacología , Antibacterianos/química , Límite de Detección , Pruebas de Sensibilidad Microbiana , Temperatura , Factores de Tiempo
18.
J Photochem Photobiol B ; 101(3): 313-20, 2010 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-20817482

RESUMEN

A single-mode tapered fiber optic biosensor was utilized for real-time monitoring of the Escherichia coli (E. coli K-12) growth in an aqueous medium. The applied fiber tapers were fabricated using heat-pulling method with waist diameter and length of 6-7µm and 3mm, respectively. The bacteria were immobilized on the tapered surface using Poly-l-Lysine. By providing the proper condition, bacterial population growth on the tapered surface increases the average surface density of the cells and consequently the refractive index (RI) of the tapered region would increase. The adsorption of the cells on the tapered fiber leads to changes in the optical characteristics of the taper. This affects the evanescent field leading to changes in optical throughput. The bacterial growth rate was monitored at room temperature by transmission of a 1558.17nm distributed feedback (DFB) laser through the tapered fiber. At the same condition, after determining the growth rate of E. coli by means of colony counting method, we compared the results with that obtained from the fiber sensor measurements. This novel sensing method, promises new application such as rapid analysis of the presence of bacteria.


Asunto(s)
Técnicas Biosensibles/métodos , Escherichia coli/crecimiento & desarrollo , Células Inmovilizadas , Escherichia coli/efectos de la radiación , Tecnología de Fibra Óptica/métodos , Concentración de Iones de Hidrógeno , Rayos Láser , Oxígeno/farmacología , Polilisina/química , Refractometría/métodos
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