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CONTEXT: Chondroitin 6 sulphate (C6S) is a glycosaminoglycan (GAG) whose accumulation is notable in mucopolysaccharidosis type IVA and VII. Flaxseed, Linum usitatissimum L. (Linaceae) (FS), is reported to have comparable properties to those of soybean, a source of genistein, a potential new treatment for MPSs. OBJECTIVE: We assess the effect of total ethanol flaxseed extract (EFSE) in an animal model of C6S accumulation. MATERIALS AND METHODS: The study was performed in adult male Wistar rats (n = 24) for 15 successive days. The animals were divided into four groups: (1) control injected with physiological saline buffer, (2) intoxicated rats injected intraperitoneally with C6S, (3) intoxicated with C6S and treated with EFSE, and (4) treated with EFSE. All groups were subjected to histopathological and biochemical studies. The antioxidant and phytochemical properties of EFSE were examined. RESULTS: Dry EFSE contains total phenols (6.28 mg EAG/g), condensed tannins (2.98 mg ECAT/g) and flavonoids (0.44 mg ECAT/g) with high antioxidant potential [RPE (IC50 = 8.37 ± 0.176), DPPH (IC50 = 12.79 ± 0.273)]. The LD50 is higher than 5000 mg/kg. The histopathological examination showed an accumulation of C6S in the C6S intoxicated group, which disappeared in the C6S-EFSE treated group. GAGs assays showed an increased excretion in the C6S intoxicated group and increased excretion of 14% in the C6S-EFSE group compared to the C6S group. DISCUSSION AND CONCLUSIONS: EFSE showed significant potential for chelation. Its use for the treatment of GAG accumulation could be suggested and generalized to a larger study population.
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Lino , Mucopolisacaridosis , Animales , Antioxidantes/farmacología , Sulfatos de Condroitina/química , Glicosaminoglicanos , Humanos , Masculino , Extractos Vegetales/farmacología , Ratas , Ratas WistarRESUMEN
Graphene oxide (GO) nanoparticles are attracting growing interest in various fields, not least because of their distinct characteristics and possible uses. However, concerns about their impact on neurological health are emerging, underlining the need for in-depth studies to assess their neurotoxicity. This study examines GO exposure's neurobehavioral and biochemical effects on the central nervous system (CNS). To this end, we administered two doses of GO (2 and 5â¯mg/kg GO) to mice over a 46-day treatment period. We performed a battery of behavioral tests on the mice, including the open field to assess locomotor activity, the maze plus to measure anxiety, the pole test to assess balance and the rotarod to measure motor coordination. In parallel, we analyzed malondialdehyde (MDA) levels and catalase activity in the brains of mice exposed to GO nanoparticles. In addition, X-ray energy dispersive (EDX) analysis was performed to determine the molecular composition of the brain. Our observations reveal brain alterations in mice exposed to GO by intraperitoneal injection, demonstrating a dose-dependent relationship. We identified behavioral alterations in mice exposed to GO, such as increased anxiety, decreased motor coordination, reduced locomotor activity and balance disorders. These changes were dose-dependent, suggesting a correlation between the amount of GO administered and the extent of behavioral alterations. At the same time, a dose-dependent increase in malondialdehyde and catalase activity was observed, reinforcing the correlation between exposure intensity and associated biochemical responses.
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Conducta Animal , Encéfalo , Grafito , Estrés Oxidativo , Animales , Grafito/toxicidad , Grafito/administración & dosificación , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratones , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Conducta Animal/efectos de los fármacos , Malondialdehído/metabolismo , Ansiedad/inducido químicamente , Catalasa/metabolismo , Actividad Motora/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Nanopartículas/toxicidad , Nanopartículas/administración & dosificaciónRESUMEN
Lead (Pb) is one of the most common heavy metals with toxicological effects on many tissues in humans as well as animals. In order to counteract the toxic effects of this metal, the administration of synthetic or natural antioxidants is thus required. The aim of this study was to examine the beneficial effect of the aqueous extract of Ononis natrix (AEON) against lead acetate-induced damage from a behavioral, biochemical, and histological point of view. Forty-eight male mice were divided into four equal groups: Ctr (control); Pb (lead acetate 1g/l); Pb + On 100 mg/kg (lead acetate 1 g/l + AEON 100 mg/kg); Pb + On 500 mg/kg (lead acetate 1 g/l + AEON 500 mg/kg). AEON was administered orally from day 21 after the start of lead exposure up to the end of the experiment. The results revealed that lead induced behavioral disorders, increased serum levels of liver markers (AST, ALT, and bilirubin), as well as kidney markers (urea and creatinine). At the same time, levels of thiobarbituric acid reactive substances (TBARS) and glutathione peroxidase (GPx) increased significantly. Moreover, Pb caused structural changes in the liver and kidneys of Pb-exposed mice. However, AEON administration significantly improved all lead-induced brain, liver, and kidney dysfunctions. Our results suggest that AEON could be a source of molecules with therapeutic potential against brain, liver, and kidney abnormalities caused by lead exposure.
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Hepatic encephalopathy (HE) is a major neuropsychological condition that occursas a result of impaired liver function. It is frequently observed in patients with advanced liver disease or cirrhosis. Memory impairment is among the symptoms of HE; the pathophysiologic mechanism for this enervating condition remains unclear. However, it is possible that neuroinflammation may be involved, as recent studies have emphasized such phenomena. Therefore, the aim of the present study is to assess short working memory (SWM) and examine the involvement of microglia in a chronic model of HE. The study was carried out with male Wistar rats that were induced by repeated thioacetamide (TAA) administration (100 mg/kg i.p injection for 10 days). SWM function was assessed through Y-maze, T-Maze, and novel object recognition (NOR) tests, together with an immunofluorescence study of microglia activation within the hippocampal areas. Our data showed impaired SWM in TAA-treated rats that was associated with microglial activation in the three hippocampal regions, and which contributed to cognitive impairment.
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Graphene oxide (GO) is a graphene derivative used for numerous applications in which biomedical uses are significant. However, for this application, the security of GO is doubtful. In this work, we synthesized this nanoparticle to assess its toxicity in male mice. In addition, we studied the effects of this nanomaterial on behavior by administering GO intraperitoneally to mice at different doses (2 mg/kg and 5 mg/kg) for five days. Subsequently, we performed biochemical analyses of blood serum and measured peroxidase and malondialdehyde (MDA) activity. Then, we performed histological sections to evaluate the brain's and liver's pathological and morphological changes. The data showed that the open field tests did not alter the locomotor activity. Furthermore, the elevated cross-maze tests showed no anxiety effect in the GO doses in the animals. The biochemical analyses indicated that GO influenced the level of biochemical parameters. Although, the oxidative stress assay showed an increase in peroxidase and MDA activity after GO intoxication. However, histopathological analysis of liver sections showed that GO caused liver inflammation, whereas, at the brain level, GO did not affect neuronal cells. The results indicate that GO caused toxic effects and that its toxicity could be mediated by oxidative stress.
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Grafito , Nanopartículas , Ratones , Masculino , Animales , Óxidos , Inyecciones Intraperitoneales , Estrés Oxidativo , PeroxidasasRESUMEN
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the degeneration of substantia nigra dopaminergic neurons. Many therapeutic strategies were explored for PD with no success. In this study, we investigated the efficacy of graphene oxide nanoparticles (GONPs) using the reserpine model of PD. Low concentrations GONPs were utilized as a therapeutic agent in many neurodegenerative diseases. We assessed the neurobehavioral alterations in the reserpine model of PD and investigated the neuroprotective and antioxidant effects of GONPs in this model. Thirty male mice were separated into three groups (N = 10): C (control); Res (Reserpine 0.25 mg/kg); Res + GONPs (Reserpine 0.25 mg/kg and GONPs 25 mg/kg). Our results showed that reserpine neurotoxicity induced hypoactivity with a significant increase of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels in the brain and brainstem. GONPs reversed the reserpine-induced hypoactivity concomitant with decreased neuronal CAT and MDA levels. These findings support the potential use of GONPs as an antioxidant agent in the central nervous system (CNS) that protects against neurodegeneration in the reserpine PD model.
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Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Enfermedad de Parkinson , Masculino , Ratones , Animales , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/etiología , Reserpina/toxicidad , Reserpina/uso terapéutico , Modelos Animales de Enfermedad , Estrés Oxidativo , Antioxidantes/metabolismo , Neuronas Dopaminérgicas , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéuticoRESUMEN
Microcystins (MCs) are cyanobacterial toxins that can negatively impact human and animal health. This study investigated the bioaccumulation, transfer, depuration, and health risks of MCs in strawberry plants (Fragaria vulgaris) and Meriones shawi animals. The plants were irrigated with 1, 5, 10, and 20 µg/L MCs for 60 days (bioaccumulation phase) and then with clean water for 30 days (depuration phase). The harvested plants (roots and leaves) were then prepared in an aliquot form and used as feed for Meriones shawi. Liquid chromatography-mass spectrometry (LC/MS/MS) was used to measure MC concentrations in plant and animal tissues. The bioaccumulation of MCs was found to be highest in the roots, followed by leaves, fruits, liver, stomach, and fecal matter. The bioaccumulation factor (BAF) was highest in perlite (8.48), followed by roots (5.01), leaves (1.55), stomach (0.87), and fecal matter (1.18), indicating that the parts with high bioaccumulation factor had high translocation of MCs. The transfer of MCs to animal organs was low, and the daily toxin intake of adult consumers of strawberry fruit irrigated with 1, 5, 10, and 20 µg/L MC did not exceed the WHO-recommended limit of 0.04 µg MC-LR/Kg of bw/day. However, fruits from plants irrigated with 10 and 20 µg/L may pose a moderate health risk to children (25 Kg bw), and Meriones' consumption of leaves may pose a significant health risk. After the depuration phase, MC concentration in perlite, roots, leaves, and fruits decreased, indicating that depuration reduced the danger of MC transmission and bioaccumulation. The study also found that glutathione reductase and glutathione S-transferase activity were essential in the depuration of MCs in the tested plants. The findings suggest that legislation regulating the quality of irrigation water in terms of MC concentrations is necessary to prevent detrimental consequences to crops and human exposure.
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Fragaria , Animales , Niño , Humanos , Gerbillinae , Microcistinas/toxicidad , Microcistinas/análisis , Espectrometría de Masas en Tándem , Cadena Alimentaria , AguaRESUMEN
At the industrial working conditions, lead exposure could induce several alterations for the human body. Subchronic lead exposure is linked with several injuries including cerebral and renal dysfunctions. The present work discusses the effects of subchronic lead toxicity (3 g/l) in drinking water during the period of treatment (6 weeks) on vasopressin system and epithelial cells in proximal tubules. Also, we aimed to evaluate the protective effect of curcumin-III administered orally by gavage (30 mg/kg BW), against subchronic Pb exposure in Meriones shawi. The biochemical and histopathological examinations demonstrate renal damages induced by lead toxicity. In addition, the behavioral and immunohistochemical studies revealed that Pb neurotoxicity exhibited an anxious behavior with a significant elevation of the vasopressin (AVP) staining within the paraventricular nuclei. The study showed also curcumin-III restored the renal alterations with an anxiolytic effect. Moreover, it restored the AVP level in the studying nuclei. Our work supports a possible link between AVP release and epithelial degeneration in the proximal tubules, and shows a new pharmacological effect of curcumin-III as an anxiolytic agent against lead toxicity.
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Curcumina , Animales , Curcumina/farmacología , Células Epiteliales , Gerbillinae , Humanos , Plomo/toxicidad , VasopresinasRESUMEN
BACKGROUND: Lead neurotoxicity is associated with numerous alterations including behavioral and neurochemical disruptions. This study evaluates the possible neurochemical disruption in the subcommissural organ (SCO) after acute (three days) and subchronic (six weeks) Pb-exposure inMeriones shawi, and the possible effect of the third active compound, curcumin-III, in mitigating the neurological alterations caused by lead exposure. METHODS: Using immunohistochemical stainings, we evaluated the Reissner's fiber (RF) secretion utilizing RF-antibody in the SCO. We compared both acute (25 mg/kg bw of Pb i.p. for 3 days) and subchronic (3 g/l of Pb in drinking water for six weeks) Pb-treatedMeriones shawi. RESULTS: The two models of lead exposure showed a significant increase in RF level in the SCO. Conversely, co-treatment with Curcumin-III at a dose of 30 mg/kg bw significantly ameliorate SCO secretory activity, as revealed by decreased RF-immunoreactivity. CONCLUSION: Together, our findings suggest the protective effects of Curcumin-III in regulating the secretory activity of the SCO after Pb-induced neuroanatomical disruptions of the SCO in Meriones.
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Curcumina , Órgano Subcomisural , Animales , Plomo/análisis , Inmunohistoquímica , Gerbillinae , Órgano Subcomisural/química , Órgano Subcomisural/fisiología , Curcumina/farmacologíaRESUMEN
Hepatic encephalopathy (HE) is a neurophysiological syndrome secondary to acute or chronic liver failure. Studies showed that HE patients exhibit a deficit in motor coordination, which may result from cerebellar functional impairment. The aim of this study is to assess the time-dependent alteration of locomotor behavior and the glial and neuronal alteration in rat with acute HE induced chemically. The study was carried out in male Sprague-Dawley rats with thioacetamide (TAA) induced acute liver failure at different stages 12 h, 24 h and 36 h. Hepatic and renal functions were assessed via various biochemical and histopathological examinations, while the cerebellum and the midbrain were examined using histology and immunohistochemistry for tyrosine hydroxylase (TH), cyclooxygenase-2 (COX-2) and glial fibrillary acidic protein (GFAP). We used as well, the open field test and the Rotarod test for assessing the locomotor activity and coordination. Our data showed a progressive loss of liver function and a progressive alteration in locomotor behavior and motor coordination in acute HE rats. In the cerebellum, we noted an increase in the degeneration of cerebellar Purkinje neurons parallel to increased COX-2 immunoreactivity together with astrocytic morphology and density changes. Likewise, in substantia nigra pars compacta, TH levels were reduced. We showed through the current study, a progressive deterioration in locomotor behavior in acute HE rats, as a result of Purkinje neurons death and a deficient dopaminergic neurotransmission, together with the morpho-functional astroglial modifications involving the oxidative stress and neuroinflammation.
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Fallo Hepático Agudo , Enfermedades Neuroinflamatorias , Animales , Astrocitos , Cerebelo , Humanos , Fallo Hepático Agudo/complicaciones , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
COVID-19 is an infectious disease that affects the respiratory system and is caused by the novel coronavirus SARS-CoV-2. It was first reported in Wuhan, China, on December 31, 2019, and has affected the entire world. This pandemic has caused serious health, economic and social problems. In this situation, the only solution to combat COVID-19 is to accelerate the development of antiviral drugs and vaccines to mitigate the virus and develop better antiviral methods and excellent diagnostic and prevention techniques. With the development of nanotechnology, nanoparticles are being introduced to control COVID-19. Graphene oxide (GO), an oxidized derivative of graphene, is currently used in the medical field to treat certain diseases such as cancer. It is characterized by very important antiviral properties that allow its use in treating certain infectious diseases. The GO antiviral mechanism is discussed by the virus inactivation and/or the host cell receptor or by the physicochemical destruction of viral species. Moreover, the very high surface/volume ratio of GO allows the fixation of biomolecules by simple absorption. This paper summarizes the different studies performed on GO's antiviral activities and discusses GO-based biosensors for virus detection and approaches for prevention.
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BACKGROUND: Studies have shown that lead (Pb) is one of hazardous heavy metals with various adverse effects on human health including mental health; Pb can induce psychiatric disorders like anxiety. In the present work, we examined the potential of bisdemethoxycurcumin (BDMC) as a neuroprotective agent against lead induced anxiety inMeriones shawi (M. shawi). METHODS: We asses, the potential of three consecutive day exposure to Pb (25 mg/kg body weight) in inducing anxiogenic effect, serotoninergic and vasopressinergic disruptions inM. shawi. This was done using neurobehavioral tests (open field, elevated plus maze), immunohistochemestry by anti-serotonin (5-HT), and anti-vasopressin (AVP) antibodies. We also measured the possible restorative potential of BDMC (30 mg/kg body weight), delivered by oral gavage. After that, a biochemical and histopathological studies were done. RESULTS: Our results showed that lead exposure for three consecutive days increases significantly the 5-HT-immunoreactivity in dorsal raphe nucleus (DRN) accompanied with a significant enhancement of AVP-immunoreactivity in the cell bodies and fibers in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. In the collecting tube, AVP binds to the V2 receptor of the epithelial cells and increases the water permeability. Our results showed clearly the epithelial cells degeneration after lead exposure, then we suggest that the increased AVP could be a response to the hydric balance disrupted after degenerative effect of lead exposure on epithelial cells. BDMC produced an anxiolytic effect in meriones. Moreover, it restored 5-HT and AVP immunoreactivity within studying nuclei. The biochemical and histopathological studies showed that Pb induced renal damages. In addition, BDMC restored the renal alterations. CONCLUSION: According to the obtained results, we suggest new pharmacological effects of BDMC; while it has an anxiolytic effect against Pb-induced anxiety by working on serotoninergic and vasopressinergic systems with an obvious restoration of the renal injuries induced by lead exposure.
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Ansiedad/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Diarilheptanoides/farmacología , Riñón/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Serotonina/metabolismo , Vasopresinas/metabolismo , Animales , Ansiedad/metabolismo , Diarilheptanoides/administración & dosificación , Gerbillinae , Inyecciones Intraperitoneales , Riñón/metabolismo , Riñón/patología , Plomo/administración & dosificación , Plomo/toxicidad , Fármacos Neuroprotectores/administración & dosificaciónRESUMEN
Aluminum (Al) is recognized potent neurotoxic metal, which causes oxidative stress leading to intracellular accumulation of reactive oxygen species (ROS) and neuronal cell death in various neurodegenerative diseases. Among several medicinal plants with beneficial effects on health, curcumin acts as a multi-functional drug with antioxidant activity. Thus, the purpose of the present study was to evaluate the protective effect of curcumin against aluminum induced-oxidative stress and astrocytes death, in vitro ad in vivo. Incubation of cultured rat astrocytes with two concentrations of Al (37 µM and 150 µM) for 1 h provoked a dose-dependent reduction of the number of living cells as evaluated by Fluorescein diacetate and lactate dehydrogenase assay. Al-treated cells exhibited a reduction of both superoxide dismutase (SOD) and catalase activities. Pretreatment of astrocytes with curcumin (81 µM) prevented Al-induced cell death. Regarding in vivo study, rats were exposed acutely during three consecutive days to three different doses of Al (25 mg/kg, 50 mg/kg and 100 mg/kg, i.p injection), together with curcumin treatment (30 mg/kg). For the chronic model, animals were exposed to Al (3 g/l) in drinking water from intrauterine age to 4 months ages, plus curcumin treatment (175 mg/kg). Data showed that both acute and chronic Al intoxication induced an obvious astrogliosis within motor cortex and hippocampus, while, such effects were restored by curcumin. We showed herein that Al was highly toxic, induced astrocytes death. Then, curcumin protected astrocytes against Al-toxicity. The cytoprotective potential of curcumin is initiated by stimulation of endogenous antioxidant system.
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Aluminio/toxicidad , Antioxidantes/farmacología , Astrocitos/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Curcumina/farmacología , Gliosis/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/uso terapéutico , Astrocitos/patología , Curcumina/uso terapéutico , Gliosis/patología , Gliosis/prevención & control , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Nanomaterials have been widely used in many fields in the last decades, including electronics, biomedicine, cosmetics, food processing, buildings, and aeronautics. The application of these nanomaterials in the medical field could improve diagnosis, treatment, and prevention techniques. Graphene oxide (GO), an oxidized derivative of graphene, is currently used in biotechnology and medicine for cancer treatment, drug delivery, and cellular imaging. Also, GO is characterized by various physicochemical properties, including nanoscale size, high surface area, and electrical charge. However, the toxic effect of GO on living cells and organs is a limiting factor that limits its use in the medical field. Recently, numerous studies have evaluated the biocompatibility and toxicity of GO in vivo and in vitro. In general, the severity of this nanomaterial's toxic effects varies according to the administration route, the dose to be administered, the method of GO synthesis, and its physicochemical properties. This review brings together studies on the method of synthesis and structure of GO, characterization techniques, and physicochemical properties. Also, we rely on the toxicity of GO in cellular models and biological systems. Moreover, we mention the general mechanism of its toxicity.
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Grafito/química , Nanopartículas/toxicidad , Algoritmos , Animales , Materiales Biocompatibles , Cristalización , Sistemas de Liberación de Medicamentos , Humanos , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Nanomedicina , Nanoestructuras , Oxígeno/química , Ratas , Reproducibilidad de los Resultados , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , Temperatura , Termogravimetría , Difracción de Rayos XRESUMEN
Dehydroepiandrosterone sulfate (DHEAS) exerts important functions in the nervous system, such as modulation of neuronal death, brain development, cognition and behavior. However, little is known about the possible interactions of this steroid with the glial cells, in particular those forming circumventricular organs (CVOs). The present study, on the one hand, was focused on the assessment of the possible effect of DHEAS on the subcommissural organ in rats. Known as one of the CVOs, the SCO can release a glycoprotein of high molecular weight named Reissner's fiber (RF) into the cerebrospinal fluid (CSF), a remarkable secretory activity. On the other hand, we examined the serotonergic innervation in the Dorsal Raphe nucleus (DRN) and the subsequent SCO. Our finding has revealed a significant increase in RF immunoreactivity within the SCO following a single i.p injection of DHEAS at a dose of 5 mg/kg B.W. A loss of serotonin (5-HT) within the DRN and fibers reaching the SCO was also observed. The present findings have brought evidence of a possible modulator potential of neurosteroids, in particular DHEAS, upon the secretory activity of the SCO. This study will open a new window for a better understanding of the main role and interaction of neurosteroids with one of the relevant circumventricular organs in the mammalian brain.
La Dehydroépiandrostérone sulfate (DHEAS) exerce des fonctions importantes dans le système nerveux central comme la modulation de la mort neuronale, le développement du cerveau, la cognition et le comportement. Cependant, très peu est connu concernant l'interaction de cette stéroïde avec les cellules gliales, en particulier celles formant les organes circumventriculaires (CVOs). La présente étude, d'une part, s'est focalisée sur l'évaluation du possible effet de la DHEAS sur l'organe sous commissural (SCO) chez le rat connu en tant qu'un des CVOs. L'organe sous commissural peut libérer une glycoprotéine de grand poids moléculaire nommée fibre de Reissner (RF) dans le liquide céphalorachidien (CSF) ; une activité sécrétoire remarquable. D'autre part, nous avons examiné l'innervation sérotoninérgique du noyau de Raphé dorsal (DRN) et l'éventuelle innervation du SCO. Nos données ont révélé une élévation significative de l'immunoréactivité à la RF dans le SCO après une seule injection i.p de la DHEAS à une dose de 5mg/kg B.W. une réduction de sérotonine (5-HT) dans le DRN et les fibres atteignant le SCO a été aussi observée. Les présentes données ont apporté une évidence d'un possible potentiel modulateur des neurostéroïdes, en particulier la DHEAS sur l'activité sécrétoire du SCO. Cette étude pourra ouvrir une nouvelle fenêtre pour une meilleure compréhension du rôle et de l'interaction des neurostéroïdes avec un des organes circumventriculaires les plus importants du cerveau des mammifères.
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Sulfato de Deshidroepiandrosterona/metabolismo , Núcleo Dorsal del Rafe/fisiología , Neuroesteroides/metabolismo , Animales , Moléculas de Adhesión Celular Neuronal/metabolismo , Inmunohistoquímica , Masculino , Ratas , Ratas Sprague-Dawley , Serotonina/fisiología , Órgano Subcomisural/metabolismoRESUMEN
This study examined the effect of prolonged water deprivation, in rat, on 5-HT and TH- immuno-expression in Dorsal Raphe Nucleus (DRN), Substantia Nigra pars compacta (SNc), Ventral Tegmental Area (VTA), and Magnus Raphe Nucleus (MRN). In parallel, we evaluated the anxiety state and pain perception in dehydrated rats. Our Findings revealed that dehydrated rats exhibited more preference for the dark compartment, suggesting that prolonged water deprivation is associated to an anxiogenic effect. After one week, 5 H T IR in the DRN of dehydrated rates showed a significant decrease. This was reversed to a significant increase post week 2 of dehydration. Our findings also demonstrated that TH-IR in DRN, MRN, SNc and VTA neuronal systems is significantly and gradually enhanced after 1-and-2-week osmotic stress. In addition, our results proved that all dehydrated rats were characterized by a significant and proportional rise of the reaction time to the nociceptive response in the hot plate test, as water deprivation duration increased, suggesting that dehydration caused a significant decrease in pain perception. Finally, the data described here clearly showed the implication of serotonin and dopamine neurotransmitter systems in the resistance to osmotic stress. Therefore, in this study, such central impairments were traduced by a few peripheral outcomes manifested by changes in mood state and nociception.
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Ansiedad/metabolismo , Percepción del Dolor/fisiología , Serotonina/metabolismo , Tirosina 3-Monooxigenasa/metabolismo , Privación de Agua/fisiología , Animales , Ansiedad/fisiopatología , Conducta Animal/fisiología , Núcleo Dorsal del Rafe/metabolismo , Núcleo Dorsal del Rafe/fisiopatología , Masculino , Núcleo Magno del Rafe/metabolismo , Núcleo Magno del Rafe/fisiopatología , Presión Osmótica/fisiología , Porción Compacta de la Sustancia Negra/metabolismo , Porción Compacta de la Sustancia Negra/fisiopatología , Ratas , Ratas Wistar , Área Tegmental Ventral/metabolismo , Área Tegmental Ventral/fisiopatologíaRESUMEN
The osmotic stress is a powerful stimulus that elicits profound peripheral and central disturbances. In the mammalian brain, osmotic stress has been associated to several glial and neuronal changes. The lack of data regarding the impact on the dopaminergic system and locomotion led us to investigate the effect of prolonged water deprivation in rat on the midbrain dopaminergic system and locomotor performance by dehydrating rats for one and two weeks. Locomotor activity and tyrosine hydroxylase (TH) expression were assessed using the open field test and immunohistochemistry respectively. Water deprivation was accompanied with a significant increment of TH expression within substantia nigra compacta (SNc) and ventral tegmental area (VTA) gradually as the duration of dehydration increases. While locomotor activity showed the inverse tendency manifested by a drop of crossed boxes number following one and two weeks of water deprivation. Our data suggest a substantial implication of midbrain dopaminergic system in the central response to the osmotic stimuli accompanied with locomotor deficiencies.
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Copper (Cu) is a transition metal and an essential trace element, but excessive levels of Cu might disturb vital functions and systems including the Central Nervous System (CNS). Curcumin has numerous beneficial effects including protective potential on the CNS toxicity. Previous studies have revealed solid evidence showing metal elements implication in the physiopathology of psychiatric disorders, principally anxiety, as well as association between stressful conditions and the inception of anxiety. In addition, it was stated that stressful condition strengthens memory. The aim of the present study was to evaluate the influence of subchronic Cu-intoxication (0.125%) for 6 weeks on the serotonergic system and anxiety state along with spatial learning and memory performance, then test the therapeutic efficacy of curcumin I (30 mg/kg B.W.). In Cu-exposed rats, we noted a significant increased innervation of 5HT in dorsal raphe nucleus and Basolateral Amygdala (BLA) outputs; this was correlated with an anxiogenic-like effect in rats subjected to elevated plus-maze test. Curcumin co-treatment prevented Cu-induced anxiety and reversed 5-HT alterations. Cu did not alter learning and memory but main spatial learning and memory performance was remarked in treated rats with curcumin in Morris water maze. Results demonstrated that subchronic Cu intoxication induced an evident anxiogenic-like effect that was alleviated with curcumin treatment, then, impairment of monoamine neurotransmitters expression may be one of the major mechanisms implicated. Therefore, curcumin may be valuable in the treatment of anxiety disorders caused by metal elements by acting as an anxiolytic agent, and in the improvement of memory performance.
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Ansiedad/inducido químicamente , Encéfalo/efectos de los fármacos , Cobre/toxicidad , Curcumina/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Animales , Encéfalo/metabolismo , Masculino , Memoria/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Wistar , Serotonina/metabolismoRESUMEN
Well-functioning of fundamental life processes and human body required metal elements especially essential elements like copper, zinc, magnesium, etc. However, other elements are very toxic for physiological functions including lead (Pb) and cadmium (Cd). Recently, cumulative investigations have interested in the role of metal elements in neurodegenerative diseases and psychiatric disorders especially anxiety and depression. Models of intoxication have been established to evaluate the neurobehavioral effects of metal element exposure via acute and chronic intoxication by metals levels in rats. This method makes available a means to recognize the association between the element level in water, diet, or serum and psychiatric dysfunctions. It allows also to assess the neurobehavioral injuries of metals in animal models and may provide a new window to understand the role metals play in the development of mood and psychiatric disorders.the role metals play in the development of mood and psychiatric disorders.
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Trastornos Mentales/etiología , Metales/efectos adversos , Enfermedades del Sistema Nervioso/etiología , Oligoelementos/efectos adversos , Enfermedad Aguda , Animales , Conducta Animal , Biomarcadores , Cadmio , Enfermedad Crónica , Cobre/efectos adversos , Cobre/metabolismo , Modelos Animales de Enfermedad , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/metabolismo , Trastornos Mentales/psicología , Metales/metabolismo , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/metabolismo , Enfermedades del Sistema Nervioso/fisiopatología , Fenotipo , Ratas , Evaluación de Síntomas , Oligoelementos/metabolismo , Zinc/efectos adversos , Zinc/metabolismoRESUMEN
Lead (Pb) is a non physiological metal that has been implicated in toxic processes affecting several organs and biological systems, including the central nervous system. Several studies have focused on changes in lead-associated neurobehavioral and neurochemical alterations that occur due to Pb exposure. The present study evaluates the effects of acute and chronic Pb acetate exposure on serotoninergic and dopaminergic systems within the dorsal raphe nucleus, regarding motor activity and anxiety behaviours. Experiments were carried out on adult male Meriones shawi exposed to acute lead acetate intoxication (25â¯mg/kg b.w., 3 i.p. injections) or to a chronic lead exposure (0,5%) in drinking water from intrauterine age to adult age. Immunohistochemical staining demonstrated that both acute and chronic lead exposure increased anti-serotonin (anti-5HT) and tyrosine hydroxylase (anti-TH) immuno-reactivities in the dorsal raphe nucleus. In parallel, our results demonstrated that a long term Pb-exposure, but not an acute lead intoxication, induced behavioural alterations including, hyperactivity (open field test), and anxiogenic like-effects. Such neurobehavioral impairments induced by Pb-exposure in Meriones shawi may be related to dopaminergic and serotoninergic injuries identified in the dorsal raphe nucleus.