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Traumatic brain injury (TBI) is a significant contributor to global mortality and disability, and there is still no specific drug available to treat cognitive deficits in survivors. Vanillic acid (VA), a bioactive phenolic compound, has shown protective effects in various models of neurodegeneration; however, its impact on TBI outcomes remains elusive. Therefore, this study aimed to elucidate the possible role of VA in ameliorating TBI-induced cognitive decline and to reveal the mechanisms involved. TBI was induced using the Marmarou impact acceleration model to deliver an impact force of 300â¯g, and treatment with VA (50â¯mg/kg; P.O.) was initiated 30â¯minutes post-TBI. The cognitive performance, hippocampal long-term potentiation (LTP), oxidative stress markers, neurological function, cerebral edema, and morphological changes were assessed at scheduled points in time. TBI resulted in cognitive decline in the passive avoidance task, impaired LTP in the perforant path-dentate gyrus (PP-DG) pathway, increased hippocampal oxidative stress, cerebral edema, neurological deficits, and neuronal loss in the rat hippocampus. In contrast, acute VA administration mitigated all the aforementioned TBI outcomes. The data suggest that reducing synaptic plasticity impairment, regulating oxidative and antioxidant defense, alleviating cerebral edema, and preventing neuronal loss by VA can be at least partially attributed to its protection against TBI-induced cognitive decline.
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Hippocampal synaptic dysfunction, oxidative stress, neuroinflammation, and neuronal loss play critical roles in the pathophysiology of diabetes-associated cognitive decline (DACD). The study aimed to investigate the effects of vanillic acid (VA), a phenolic compound, against DACD and explore the potential underlying mechanisms. Following confirmation of diabetes, rats were treated with VA (50 mg/kg/day; P.O.) or insulin (6 IU/rat/day; S.C.) for 8 consecutive weeks. The cognitive performance of the rats was evaluated using passive-avoidance and water-maze tasks. Long-term potentiation (LTP) was induced at hippocampal dentate gyrus (DG) synapses in response to high-frequency stimulation (HFS) applied to the perforant pathway (PP) to evaluate synaptic plasticity. Oxidative stress factors, inflammatory markers, and histological changes were evaluated in the rat hippocampus. This study showed that streptozotocin (STZ)-induced diabetes caused cognitive decline that was associated with inhibition of LTP induction, suppression of enzymatic antioxidant activities, enhanced lipid peroxidation, elevated levels of inflammatory proteins, and neuronal loss. Interestingly, chronic treatment with VA alleviated blood glucose levels, improved cognitive decline, ameliorated LTP impairment, modulated oxidative-antioxidative status, inhibited inflammatory response, and prevented neuronal loss in diabetic rats at a level comparable to insulin therapy. The results suggest that the antihyperglycemic, antioxidative, anti-inflammatory, and neuroplastic properties of VA may be the mechanisms behind its neuroprotective effect against DACD.
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Disfunción Cognitiva , Diabetes Mellitus Experimental , Fármacos Neuroprotectores , Ratas , Animales , Diabetes Mellitus Experimental/complicaciones , Fármacos Neuroprotectores/farmacología , Ácido Vanílico/farmacología , Ratas Wistar , Hipocampo , Antioxidantes/farmacología , Plasticidad Neuronal , Disfunción Cognitiva/patología , InsulinaRESUMEN
Lead (Pb) is a well-known toxic pollutant that has negative effects on behavioral functions. Sesamin, a phytonutrient of the lignan class, has shown neuroprotective effects in various neurological disorder models. The present study was undertaken to evaluate the putative protective effects of sesamin against Pb-induced behavioral deficits and to identify the role of oxidative stress in male rats. The rats were exposed to 500 ppm of Pb acetate in their drinking water and simultaneously treated orally with sesamin at a dose of 30 mg/kg/day for eight consecutive weeks. Standard behavioral paradigms were used to assess the behavioral functions of the animals during the eighth week of the study. Subsequently, oxidative stress factors were evaluated in both the cerebral cortex and hippocampal regions of the rats. The results of this study showed that Pb exposure triggered anxiety-/depression-like behaviors and impaired object recognition memory, but locomotor activity was indistinguishable from the normal control rats. These behavioral deficiencies were associated with suppressed enzymatic and non-enzymatic antioxidant levels, and enhanced lipid peroxidation in the investigated brain regions. Notably, correlations were detected between behavioral deficits and oxidative stress generation in the Pb-exposed rats. Interestingly, sesamin treatment mitigated anxio-depressive-like behaviors, ameliorated object recognition memory impairment, and modulated oxidative-antioxidative status in the rats exposed to Pb. The results suggest that the anti-oxidative properties of sesamin may be one of the underlying mechanisms behind its beneficial effect in ameliorating behavioral deficits associated with Pb exposure.
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Dioxoles , Plomo , Lignanos , Ratas , Animales , Masculino , Ratas Wistar , Plomo/farmacología , Estrés Oxidativo , Antioxidantes/farmacología , Lignanos/farmacología , Lignanos/uso terapéuticoRESUMEN
Ischemic stroke (IS) stands as a prominent cause of mortality and long-term disability around the world. It arises primarily from a disruption in cerebral blood flow, inflicting severe neural injuries. Hence, there is a pressing need to comprehensively understand the intricate mechanisms underlying IS and identify novel therapeutic targets. Recently, long noncoding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules with the potential to attenuate pathogenic mechanisms following IS. Among these lncRNAs, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) has been extensively studied due to its involvement in the pathophysiological processes of IS. In this review, we provide an in-depth analysis of the essential role of MALAT1 in the development and progression of both pathogenic and protective mechanisms following IS. These mechanisms include oxidative stress, neuroinflammation, cell death signaling, blood brain barrier dysfunction, and angiogenesis. Furthermore, we summarize the impact of MALAT1 on the susceptibility and severity of IS. This review highlights the potential risks associated with the therapeutic use of MALAT1 for IS, which are attributable to the stimulatory action of MALAT1 on ischemia/reperfusion injury. Ultimately, this review sheds light on the potential molecular mechanisms and associated signaling pathways underlying MALAT1 expression post-IS, with the aim of uncovering potential therapeutic targets.
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Parkinson's disease (PD) is a common age-related neurodegenerative disorder whose pathogenesis is not completely understood. Mitochondrial dysfunction and increased oxidative stress have been considered as major causes and central events responsible for the progressive degeneration of dopaminergic (DA) neurons in PD. Therefore, investigating mitochondrial disorders plays a role in understanding the pathogenesis of PD and can be an important therapeutic target for this disease. This study discusses the effect of environmental, genetic and biological factors on mitochondrial dysfunction and also focuses on the mitochondrial molecular mechanisms underlying neurodegeneration, and its possible therapeutic targets in PD, including reactive oxygen species generation, calcium overload, inflammasome activation, apoptosis, mitophagy, mitochondrial biogenesis, and mitochondrial dynamics. Other potential therapeutic strategies such as mitochondrial transfer/transplantation, targeting microRNAs, using stem cells, photobiomodulation, diet, and exercise were also discussed in this review, which may provide valuable insights into clinical aspects. A better understanding of the roles of mitochondria in the pathophysiology of PD may provide a rationale for designing novel therapeutic interventions in our fight against PD.
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Enfermedades Mitocondriales , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/metabolismo , Mitocondrias/metabolismo , Enfermedades Mitocondriales/patología , Estrés Oxidativo/fisiología , Neuronas Dopaminérgicas/metabolismoRESUMEN
Alzheimer's disease (AD), the most common form of dementia, is characterized by a progressive decline in cognitive performance and memory formation. The present study was designed to investigate the effect of policosanol (PCO) on cognitive function, oxidative-antioxidative status, and amyloid-beta (Aß) plaque formation in an AD rat model induced by intracerebroventricular (ICV) injection of Aß1-40. Healthy adult male Wistar rats were randomly divided into seven groups: control, sham (5 µL, ICV injection of phosphate-buffered saline), AD model (5 µL, ICV injection of Aß), acacia gum (50 mg/kg, 8 weeks, gavage), PCO (50 mg/kg, 8 weeks, gavage), AD + acacia gum (50 mg/kg, 8 weeks, gavage), and AD + PCO (50 mg/kg, 8 weeks, gavage). During the ninth and tenth weeks of the study, the cognitive function of the rats was assessed by commonly used behavioral paradigms. Subsequently, oxidative-antioxidative status was examined in the serum. Moreover, compact Aß plaques were detected by Congo red staining. The results showed that injection of Aß impaired recognition memory in the novel object recognition test, reduced the spatial cognitive ability in the Morris water maze, and alleviated retention and recall capability in the passive avoidance task. Additionally, injection of Aß resulted in increased total oxidant status, decreased total antioxidant capacity, and enhanced Aß plaque formation in the rats. Intriguingly, PCO treatment improved all the above-mentioned neuropathological changes in the Aß-induced AD rats. The results suggest that PCO improves Aß-induced cognitive decline, possibly through modulation of oxidative-antioxidative status and inhibition of Aß plaque formation.
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Enfermedad de Alzheimer , Ratas , Masculino , Animales , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/inducido químicamente , Ratas Wistar , Goma Arábiga/efectos adversos , Trastornos de la Memoria/complicaciones , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/patología , Péptidos beta-Amiloides/toxicidad , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Modelos Animales de Enfermedad , Aprendizaje por Laberinto , Hipocampo/patología , Fragmentos de Péptidos/toxicidadRESUMEN
Lead (Pb) is a highly poisonous environmental pollutant that can induce cognitive decline. Chrysin, a natural flavonoid compound, has anti-oxidative, anti-inflammatory, and neuroprotective properties in different neurodegenerative disorders. The present study was designed to examine the putative effects of chrysin against Pb-induced cognitive impairment and the possible involved mechanisms. Adult male Wistar rats were exposed to Pb acetate (500â¯ppm in standard drinking water) either alone or in combination with daily oral administration of chrysin (30â¯mg/kg) for eight consecutive weeks. During the eight-week period of the study, the cognitive capacity of the rats was evaluated by employing both novel object recognition and passive avoidance tests. On day 56, hippocampal synaptic plasticity (long-term potentiation; LTP) was recorded in perforant path-dentate gyrus (PP-DG) synapses to assess field excitatory postsynaptic potentials (fEPSPs) slope and population spike (PS) amplitude. Subsequently, pro- and anti-inflammatory cytokines and histological changes were evaluated in the cerebral cortex and hippocampus of the rats. Moreover, Pb levels in blood and brain tissues were assessed. The results showed that Pb exposure causes cognitive decline, inhibition of hippocampal LTP induction, imbalance of pro- and anti-inflammatory cytokines, enhancement of Pb levels in blood and brain tissues, and neuronal loss. However, chrysin treatment improved cognitive dysfunction, ameliorated hippocampal LTP impairment, modulated inflammatory status, reduced Pb concentration, and prevented neuronal loss in the Pb-exposed rats. The results suggest that chrysin alleviates Pb-induced cognitive deficit, possibly through mitigation of hippocampal synaptic dysfunction, modulation of inflammatory status, reduction of Pb concentration, and prevention of neuronal loss.
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Disfunción Cognitiva , Giro Dentado , Animales , Ratas , Masculino , Giro Dentado/fisiología , Ratas Wistar , Potenciación a Largo Plazo , Potenciales Postsinápticos Excitadores , Plasticidad Neuronal , Hipocampo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/prevención & controlRESUMEN
BACKGROUND: Alzheimer's disease (AD) is the most progressive form of neurodegenerative disease resulting in cognitive and non-cognitive deficits. Aluminum is recognized as a risk factor for the etiology, pathogenesis, and progression of AD. The present study was designed to determine the effects of p-coumaric acid (p-CA), a phenolic compound, on spatial cognitive ability and non-cognitive functions and to identify the role of oxidative stress and inflammation in an AD rat model induced by aluminum chloride (AlCl3). METHODS: Both AlCl3 (100 mg/kg/day; P.O.) and p-CA (100 mg/kg/day; P.O.) treatments were given for six consecutive weeks. During the fifth and sixth weeks of the treatment period, the cognitive and non-cognitive functions of the rats were assessed using standard behavioral tests. Additionally, oxidative-antioxidative status, inflammatory markers, and histological changes were evaluated in the cerebral cortex and hippocampal regions of the rats. RESULTS: The results of this study showed that AlCl3 exposure enhanced anxiety-/depression-like behaviors, reduced locomotor/exploratory activities, and impaired spatial learning and memory. These cognitive and non-cognitive disturbances were accompanied by increasing oxidative stress, enhancing inflammatory response, and neuronal loss in the studied brain regions. Interestingly, treatment with p-CA alleviated all the above-mentioned neuropathological changes in the AlCl3-induced AD rat model. CONCLUSION: The findings suggest that both anti-oxidative and anti-inflammatory properties of p-CA may be the underlying mechanisms behind its beneficial effect in preventing neuronal loss and improving cognitive and non-cognitive deficits associated with AD.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Ratas , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Cloruro de Aluminio/efectos adversos , Aluminio/efectos adversos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Ratas Wistar , Modelos Animales de Enfermedad , Estrés Oxidativo , Inflamación/tratamiento farmacológico , Inflamación/patología , Hipocampo , Fármacos Neuroprotectores/farmacología , Aprendizaje por LaberintoRESUMEN
BACKGROUND: Lead (Pb) is one of the most hazardous pollutants that induce a wide spectrum of neurological changes such as learning and memory deficits. Sesamin, a phytonutrient of the lignan class, exhibits anti-inflammatory, anti-apoptotic, and neuroprotective properties. The present study was designed to investigate the effects of sesamin against Pb-induced learning and memory deficits, disruption of hippocampal theta and gamma rhythms, inflammatory response, inhibition of blood δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, Pb accumulation, and neuronal loss in rats. METHODS: Sesamin treatment (30 mg/kg/day; P.O.) was started simultaneously with Pb acetate exposure (500 ppm in standard drinking water) in rats, and they continued for eight consecutive weeks. RESULTS: The results showed that chronic exposure to Pb disrupted the learning and memory functions in both passive-avoidance and water-maze tests, which was accompanied by increase in spectral theta power and theta/gamma ratio, and a decrease in spectral gamma power in the hippocampus. Additionally, Pb exposure resulted in an enhanced tumor necrosis factor-alpha (TNF-α) content, decreased interleukin-10 (IL-10) production, inhibited blood δ-ALA-D activity, increased Pb accumulation, and neuronal loss of rats. In contrast, sesamin treatment improved all the above-mentioned Pb-induced pathological changes. CONCLUSION: This data suggests that sesamin could improve Pb-induced learning and memory deficits, possibly through amelioration of hippocampal theta and gamma rhythms, modulation of inflammatory status, restoration of the blood δ-ALA-D activity, reduction of Pb accumulation in the blood and the brain tissues, and prevention of neuronal loss.
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Plomo , Lignanos , Animales , Dioxoles , Ritmo Gamma , Hipocampo , Plomo/toxicidad , Lignanos/farmacología , Lignanos/uso terapéutico , Aprendizaje por Laberinto , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/patología , RatasRESUMEN
Neuroinflammation and loss of neurotrophic support have key roles in the pathophysiology of diabetes-associated behavioral deficits (DABD). Sesamin (Ses), a major lignan of sesame seed and its oil, shows anti-hyperglycemic, anti-oxidative, and neuroprotective effects. The present study was designed to assess the potential protective effects of Ses against DABD and investigate the roles of inflammatory markers and neurotrophic factors in streptozotocin (STZ)-induced diabetic rats. After confirmation of diabetes, Ses (30 mg/kg/day; P.O.) or insulin (6 IU/rat/day; S.C.) was administered to rats for eight consecutive weeks. During the eighth-week period of the study, behavioral functions of the animals were evaluated by employing standard behavioral paradigms. Moreover, inflammation status, neurotrophic factors, and histological changes were assessed in the cerebral cortex and hippocampal regions of the rats. The results of behavioral tests showed that STZ-induced diabetes increased anxiety-/depression-like behaviors, decreased locomotor/exploratory activities, and impaired passive avoidance learning and memory. These DABD were accompanied by neuroinflammation, lack of neurotrophic support, and neuronal loss in both cerebral cortex and hippocampus of the rats. Intriguingly, chronic treatment with Ses improved all the above-mentioned diabetes-related behavioral, biochemical, and histological deficits, and in some cases, it was even more effective than insulin therapy. In conclusion, the results suggest that Ses was capable of improving DABD, which might be ascribed, at least partly, to the reduction of blood glucose level, inhibition of neuroinflammation, and potentiation of neurotrophic factors.
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Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Dioxoles/farmacología , Inflamación/metabolismo , Lignanos/farmacología , Trastornos de la Memoria/tratamiento farmacológico , Factores de Crecimiento Nervioso/metabolismo , Animales , Antioxidantes/farmacología , Ansiedad/etiología , Ansiedad/patología , Ansiedad/psicología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Depresión/etiología , Depresión/patología , Depresión/psicología , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inflamación/patología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/etiología , Trastornos de la Memoria/patología , Trastornos de la Memoria/psicología , Fármacos Neuroprotectores/farmacología , RatasRESUMEN
RATIONALE: Cortical and hippocampal neuronal apoptosis and neuroinflammation are associated with behavioral deficits following traumatic brain injury (TBI). OBJECTIVES: The present study was designed to investigate the potential protective effects of flavonoid chrysin against TBI-induced vestibulomotor impairment, exploratory/locomotor dysfunctions, recognition memory decline, and anxiety/depression-like behaviors, as well as the verified possible involved mechanisms. METHODS: Chrysin (25, 50, or 100 mg/kg/day; P.O.) was administered to rats immediately after diffuse TBI induction, and it was continued for 3 or 14 days. Behavioral functions were assessed by employing standard behavioral paradigms at scheduled points in time. Three days post-TBI, inflammation status was assayed in both cerebral cortex and hippocampus using ELISA kits. Moreover, apoptosis and expression of Bcl-2 family proteins were examined by TUNEL staining and immunohistochemistry, respectively. RESULTS: The results indicated that treatment with chrysin improved vestibulomotor dysfunction, ameliorated recognition memory deficit, and attenuated anxiety/depression-like behaviors in the rats with TBI. Chrysin treatment also modulated inflammation status, reduced apoptotic index, and regulated Bcl-2 family proteins expression in the brains of rats with TBI. CONCLUSIONS: In conclusion, the results suggest that chrysin could be beneficial for protection against TBI-associated behavioral deficits, owing to its anti-apoptotic and anti-inflammatory properties.
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Ansiedad/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Depresión/tratamiento farmacológico , Flavonoides/uso terapéutico , Trastornos de la Memoria/tratamiento farmacológico , Reconocimiento en Psicología/efectos de los fármacos , Animales , Ansiedad/etiología , Ansiedad/psicología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/psicología , Depresión/etiología , Depresión/psicología , Flavonoides/farmacología , Masculino , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/psicología , Ratas , Ratas WistarRESUMEN
AIMS: Hippocampal oxidative stress and apoptosis of CA1 neurons play significant roles in the pathophysiology of diabetes-associated cognitive decline (DACD). The present study was aimed to elucidate the putative effects of sesamin, a major lignan of sesame seed, against DACD, and possible involvement of anti-oxidative and anti-apoptotic mechanisms. MAIN METHODS: Fifty adult male Wistar rats were randomly divided into control, control-sesamin (30â¯mg/kg/day), diabetic, diabetic-sesamin (30â¯mg/kg/day), and diabetic-insulin (6â¯IU/rat/day) groups. Diabetic rats were treated with sesamin (P.O.) or insulin (S.C.) for eight consecutive weeks. Cognitive performance was evaluated in a Morris Water Maze (MWM) test; in addition, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) concentrations were assayed in the hippocampus using assay kits. Moreover, hematoxylin-eosin (HE), TUNEL, and immunohistochemistry (IHC) stainings were conducted to evaluate histological changes, the apoptosis status and expression of pro- and anti-apoptotic proteins in the hippocampal CA1 neurons, respectively. KEY FINDINGS: The results showed that diabetes reduced the spatial cognitive ability in MWM, which was accompanied by decrease in SOD, CAT, and GPx activities and increase in MDA level in the hippocampus. Additionally, diabetes resulted in neuronal loss, enhanced apoptotic index, elevated the expression of pro-apoptotic Bax protein, and decreased the expression of anti-apoptotic Bcl-2 protein in the hippocampal CA1 neurons. Interestingly, sesamin treatment improved all the above-mentioned deficits of diabetes at a comparable level with insulin therapy. SIGNIFICANCE: The results suggest that sesamin could be a promising potential therapeutic agent against DACD, possibly through its intertwined anti-hyperglycemic, anti-oxidative, and anti-apoptotic properties.
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Disfunción Cognitiva/tratamiento farmacológico , Complicaciones de la Diabetes/tratamiento farmacológico , Dioxoles/farmacología , Lignanos/farmacología , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Dioxoles/metabolismo , Glutatión Peroxidasa/metabolismo , Hipocampo/metabolismo , Insulina/farmacología , Lignanos/metabolismo , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
AIMS: Diabetes mellitus (DM), a chronic metabolic disease, is associated with behavioral deficits. It has been suggested that ellagic acid (EA), a natural polyphenol compound, has potent anti-diabetic, anti-inflammatory, and neuroprotective properties. The present study was aimed to explore the potential protective effects of EA against diabetes-associated behavioral deficits and verified possible involved mechanisms. MAIN METHODS: Fifty adult male Wistar rats were randomly divided into five groups: i.e., CON: normal rats treated with vehicle (5â¯ml/kg/day; P.O.), EA: normal rats treated with EA (50â¯mg/kg/day; P.O.), STZ: diabetic rats treated with vehicle (5â¯ml/kg/day; P.O.), STZâ¯+â¯INS: diabetic rats treated with insulin (6â¯IU/rat/day; S.C.), STZâ¯+â¯EA: diabetic rats treated with EA (50â¯mg/kg/day; P.O.). All the groups were under treatment for eight consecutive weeks. During the seventh and eighth weeks, behavioral functions of the rats were assessed by commonly used behavioral tests. Subsequently, pro- and anti-inflammatory cytokines, neurotrophic factors, and also histological changes were evaluated in both cerebral cortex and hippocampus of the rats. KEY FINDINGS: Chronic EA treatment attenuated anxiety/depression-like behaviors, improved exploratory/locomotor activities, and ameliorated cognitive deficits in diabetic rats. These results were accompanied by decreased blood glucose levels, modulation of inflammation status, improved neurotrophic support, and amelioration of neuronal loss in diabetic rats. In some aspects, treatment with EA was even more effective than insulin therapy. SIGNIFICANCE: The current work's data confirms that EA could potentially serve as a novel, promising, and accessible protective agent against diabetes-associated behavioral deficits, owing to its anti-hyperglycemic, anti-inflammatory, and neurotrophic properties.
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Conducta Animal/efectos de los fármacos , Trastornos del Conocimiento/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Ácido Elágico/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Glucemia/metabolismo , Corteza Cerebral/efectos de los fármacos , Trastornos del Conocimiento/etiología , Hipocampo/efectos de los fármacos , Masculino , Ratas , Ratas WistarRESUMEN
Oxidative stress has a major role in progression of diabetes-related behavioral deficits. It has been suggested that Aloe vera has anti-diabetic, antioxidative, and neuroprotective effects. The present study was designed to determine the effects of Aloe vera gel on behavioral functions, oxidative status, and neuronal viability in the hippocampus of streptozotocin (STZ)-induced diabetic rats. Fifty five adult male Wistar rats were randomly divided into five groups, including: control (normal saline 8ml/kg/day; P.O.), diabetic (normal saline 8ml/kg/day; P.O.), Aloe vera gel (100mg/kg/day; P.O.), diabetic+Aloe vera gel (100mg/kg/day; P.O.) and diabetic+NPH insulin (10 IU/kg/day; S.C.). All treatments were started immediately following confirmation of diabetes in diabetic groups and were continued for eight weeks. Behavioral functions were evaluated by employing standard behavioral paradigms. Additionally, oxidative status and neuronal viability were assessed in the hippocampus. The results of behavioral tests showed that diabetes enhanced anxiety/depression-like behaviors, reduced exploratory and locomotor activities, decreased memory performance, and increased stress related behaviors. These changes in diabetic rats were accompanied by increasing oxidative stress and neuronal loss in the hippocampus. Interestingly, eight weeks of treatment with Aloe vera gel not only alleviated all the mentioned deficits related to diabetes, but in some aspects, it was even more effective than insulin. In conclusion, the results suggest that both interrelated hypoglycemic and antioxidative properties of Aloe vera gel are possible mechanisms that improve behavioral deficits and protect hippocampal neurons in diabetic animals.
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Antioxidantes/uso terapéutico , Reacción de Prevención/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Preparaciones de Plantas/uso terapéutico , Animales , Antioxidantes/farmacología , Reacción de Prevención/fisiología , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/psicología , Humanos , Hipoglucemiantes/farmacología , Masculino , Estrés Oxidativo/fisiología , Preparaciones de Plantas/farmacología , Ratas , Ratas Wistar , EstreptozocinaRESUMEN
Diabetes mellitus is one of the most common causes of neuropathy. Although antioxidant and antidiabetic effects of the aqueous extract of purslane (Portulaca oleracea) (AEOP) have been demonstrated before by other researchers, we did not find any study that assessed the psychobiological effects of AEOP in diabetes induced animals. Thirty ovariectomized (OVX) female Wistar rats were randomly divided into 3 groups of control, Dia and Dia+AEOP. The latter group was orally treated by 300 mg/kg of AEOP for 35 days. Dia and Dia+AEOP groups were made diabetic by IP injection of 60 mg/kg of streptozotocin (STZ). The psychobiological effects of AEOP were assessed by Morris water maze (MWM), elevated plus maze (EPM), forced swimming test (FST) and tail pinch stressor (TPS). AEOP significantly decreased hyperglycemia (p<0.001). Diabetes significantly decreased their spatial cognitive performance at the training trial as well as the total distance traveled at the probe trial in MWM (p<0.05). All the diabetes related deficits at training trials were improved by AEOP treatment (p<0.05). AEOP treatment not only improved the motor deficit of Dia group in EPM, but also showed anxiolytic effects compared to both control and Dia groups (p<0.05). In the FST, no differences were observed between any groups (p>0.05). Diabetes significantly increased their non-functional masticatory activity in TPS (p≤0.001) while it was improved in Dia+AEOP group. We showed that AEOP has significant anxiolytic effects and it can improve spatial cognitive performance, locomotor deficit and stress in diabetic OVX rats.
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Steadily increased use of silver nanoparticles (Ag-NPs), has increased the amount of its exposure to humans and animals. Current scarce knowledge about the influences of prenatal exposure to Ag-NPs on postnatal outcomes, motivated us to investigate whether being exposed to it during pregnancy has any effects on neurobehavioral development of the adult offspring. Thirty virgin female NMRI mice were mated and treated subcutaneously once every three days from gestation day 3 until delivery, by 0, 0.2 and 2 mg/kg of bodyweight (BW) of Ag-NPs. Behavioral functions of adult offspring including spatial memory, passive avoidance learning, stress, anxiety-like behaviors and locomotor activities were assessed by commonly used neurobehavioral paradigms and the results were compared according to treatment and sex. Prenatal exposure to Ag-NPs significantly impaired their cognitive behavior in the Morris water maze. Although no evidence was observed indicating more anxiety-like behaviors in the treated offspring in the elevated plus maze, the number of defecations and leanings in the open field assay and number of passages in the light-dark box were greater in groups prenatally treated by Ag-NPs. Most of the impairments were more apparent in the offspring which had been prenatally exposed to high doses of Ag-NPs, particularly female ones. The present study indicated that the exposure of pregnant animals to Ag-NPs may lead to various neurobehavioral disorders in their offspring. Thus, more attention should be paid to avoid exposure to Ag-NPs, especially from pregnant females.