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BACKGROUND: Autism spectrum disorder (ASD) is the fastest-growing child neuropsychiatric condition. Cognitive dysfunctions such as memory impairments are experienced by patients along with social disturbances and repetitive/stereotypic movements. We have used the radial arm maze (RAM), for measurement of working and reference memory errors in an animal model of autism. In addition, the potential effects of agmatine, an endogenous NMDA antagonist, on RAM performance and autistic-like behaviors were assessed. METHODS: Autism was modeled by valproic acid (VPA) administration at gestational Day 12.5. Autism-associated behaviors in male offspring were examined in an open field test (OFT) and three-chambered test (TCT) on postnatal days 50-51. Thereafter, the animals were trained in the RAM (PND 55) until they attained the criteria of 80% correct choices during five consecutive trials. Forty-eight hours after the acquisition of criteria, agmatine was injected 30 min before subsequent behavioral testing, which included the retention phase of the RAM, OFT, and TCT. RESULTS: VPA-treated and intact rats showed the same performance in RAM, and acute injection of agmatine rescued social and anxiety-like behavior induced by VPA without the effect on RAM. CONCLUSION: In a rat model of autism, spatial learning, and memory did not change. Agmatine rescued social and anxiety-like behavior in autistic animals.
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Agmatina , Trastorno Autístico , Conducta Animal , Modelos Animales de Enfermedad , Aprendizaje por Laberinto , Animales , Agmatina/farmacología , Masculino , Ratas , Aprendizaje por Laberinto/efectos de los fármacos , Trastorno Autístico/tratamiento farmacológico , Trastorno Autístico/psicología , Conducta Animal/efectos de los fármacos , Memoria/efectos de los fármacos , Ácido Valproico/farmacología , Femenino , EmbarazoRESUMEN
The hallmark of aluminum phosphide (AlP) poisoning is heart failure in victims which is associated with reactive oxygen species (ROS), mitochondrial dysfunction, oxidative stress, alteration in antioxidant defense system and depletion of ATP in cardiomyocytes. In the present study, we hypothesized that the injection of isolated mitochondria into blood or mitochondrial transplantation can likely create a primary target for phosphine released from AlP and inhibit AlP-induced mortality and cardiotoxicity in rat. Male, Wistar, healthy and adult rats were randomly divided into 5 groups as control, AlP (12.5 mg/kg, orally), AlP + mitochondria (125 µg/kg), AlP + mitochondria (250 µg/kg) and mitochondria (250 µg/kg) alone. Functional and intact mitochondria isolated from rat heart and transplantation was carried out via tail vein, 30 min after exposure to AlP. Survival rate, histopathological alterations, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters were monitored and analyzed during 30 days. We found that injection of healthy mitochondria into blood at concentrations of 125 and 250 125 µg/ml significantly increased the survival of rats up to 40% and 56.25% respectively, during 30 days. Moreover, we observed that mitochondria injection into blood decreased histopathological damages, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters. To our knowledge, the current study is the first report in the literature that demonstrated good therapeutic effects of mitochondrial transplantation in AlP-induced mortality and cardiotoxicity. The findings of the present study suggests that injection of exogenous mitochondria into blood could be an effective therapeutic strategy in treating AlP poisoning.
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Originally sourced from plants, Bergenin has been used as a medicinal compound in traditional medicine for centuries, and anecdotal reports suggest a wide range of therapeutic uses. Naturally-occurring and lab-synthesized Bergenin, as well as some of its related compounds, have been shown in in vivo and in vitro studies to alter activity of several enzymes and proteins critical in cellular functioning, including reelin, GSK-3ß, Lingo-1, Ten-4, GP-43, Aß 1-42, P-tau, SOD1,2, GPx, Glx1, NQO1, HO1, PPAR-É£, BDNF, VEGF, and STAT6. Additionally, Bergenin alters levels of several cytokines, such as IL-6, IL-1ß, TNF-α, and TGF-ß. Behavioral and cellular effects of Bergenin have been shown to involve PI3K/Akt, NF-κB, PKC, Nrf2, and Sirt1/FOXO3a pathways. These pathways, enzymes, and proteins have been shown to be important in normal neurological functioning, and/or dysfunctions in these pathways and proteins have been shown to be important in several neuro-based disorders or diseases, which suggests that Bergenin could be therapeutic in management of neuropsychiatric conditions or neurological disorders. In preclinical studies, Bergenin has been shown to be useful for the management of Alzheimer's disease, Parkinson's disease, anxiety, depression, addiction, epilepsy, insomnia, stroke, and potentially, state control. Our review aims to summarize current evidence supporting the conclusion that Bergenin could play a role in treating various neuro-based disorders and that future studies should be conducted to evaluate the mechanisms by which Bergenin could exert its therapeutic effects.
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Curcumin, a natural compound derived from the turmeric plant (Curcuma longa), has garnered significant attention for its diverse neuroprotective properties. Curcumin has been widely recognized for its remarkable anti-inflammatory, antioxidant, and anti-apoptotic effects, which have shown great potential in the treatment of various disorders, encompassing psychiatric and neurodegenerative diseases. In this review, we delve into the protective effects of curcumin against drugs of abuse, including morphine, methamphetamine, cocaine, nicotine, and alcohol, with a particular focus on the underlying mechanisms from a neuroscience perspective. Overall, curcumin demonstrates promising effects against the neurotoxicity induced by abused drugs through a wide range of mechanisms. These include the modulation of inflammatory cytokines, maintenance of ion homeostasis, epigenetic regulation, enhancement of antioxidant capacity, as well as the activation of the cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) signaling pathways. These findings suggest that curcumin emerges as a promising therapeutic agent in combatting the detrimental effects induced by drugs of abuse, and further research is warranted to fully comprehend the molecular pathways and optimize its utilization for the prevention and treatment of substance abuse-related neurotoxicity.
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Bedsores impose an important challenge to the healthcare system. Se-baring probiotics are considered effective agents in wound healing and inflammation reduction via several pathways. The present study focused on the administration of a Se-enriched probiotic, originally obtained from a traditional dairy product for bedsore healing. Daily doses of the probiotic were administered to 20 ICU patients for 14 days and the wound healing criteria were compared with those of the same group of ICU patients as control, both groups suffering from stages I and II bedsore (a randomized, double-blind, controlled clinical trial). The administered Se-enriched probiotic decreased the bedsore healing period significantly (on average by 2.4 days, P-value: 0.039), as well as bedsore size (on average by 7 mm2, nonsignificant) and bedsore grade (10%, nonsignificant) in the treatment group more efficiently than the control group. Some key laboratory parameters associated with inflammation were also improved in patients receiving the Se-supplemented probiotic. The limitations of this study include the low number of patients meeting inclusion criteria within the timeframe of the study, and the impossibility of following up patients after discharge from the ICU. In summary, this study revealed the effectiveness of the Se-enriched probiotic in bedsore improvement, suggesting consideration of the enriched probiotic as an auxiliary agent in bedsore management.
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Essential tremor (ET) is a neurological disease that impairs motor and cognitive functioning. A variant of the Lingo-1 genetic locus is associated with a heightened ET risk, and increased expression of cerebellar Lingo-1. Lingo-1 has been associated with neurodegenerative processes; however, neuroprotection from ET-associated degeneration can be conferred by the protein Sirt1. Sirt1 activity can be promoted by Resveratrol (Res) and 1,25-dihydroxyvitamin D3 (VitD3), and thus these factors may exert neuroprotective properties through a Sirt1 mechanism. As Res and VitD3 are linked to Sirt1, enhancing Sirt1 could counteract the negative effects of increased Lingo-1. Therefore, we hypothesized that a combination of Res-VitD3 in a harmaline injection model of ET would modulate Sirt1 and Lingo-1 levels. As expected, harmaline exposure (10 mg/kg/every other day; i.p.) impaired motor coordination, enhanced tremors, rearing, and cognitive dysfunction. When Res (5 mg/kg/day; i.p.) and VitD3 (0.1 mg/kg/day; i.p.) were given to adult rats (n = 8 per group) an hour before harmaline, tremor severity, rearing, and memory impairment were reduced. Individual treatment with Res and VitD3 decreased Lingo-1 gene expression levels in qPCR assays. Co-treatment with Res and VitD3 increased and decreased Sirt1 and Lingo-1 gene expression levels, respectively, and in some cases, beneficial effects on behavior were noted, which were not seen when Res or VitD3 were individually applied. Taken together, our study found that Res and VitD3 improved locomotor and cognitive deficits, modulated Sirt1 and Lingo-1. Therefore, we would recommend co-treatment of VitD3 and Res to leverage complementary effects for the management of ET symptoms.
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Temblor Esencial , Harmalina , Resveratrol , Sirtuina 1 , Animales , Resveratrol/farmacología , Resveratrol/uso terapéutico , Sirtuina 1/metabolismo , Sirtuina 1/genética , Masculino , Ratas , Temblor Esencial/tratamiento farmacológico , Temblor Esencial/metabolismo , Temblor Esencial/genética , Harmalina/farmacología , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Calcitriol/farmacología , Calcitriol/uso terapéutico , Modelos Animales de Enfermedad , Conducta Animal/efectos de los fármacos , Ratas Sprague-Dawley , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéuticoRESUMEN
The likelihood of substance dependency in offspring is increased in cases when there is a family history of drug or alcohol use. Mothering is limited by maternal addiction because of the separation. Maternal separation (MS) leads to the development of behavioural and neuropsychiatric issues in the future. Despite the importance of this issue, empirical investigations of the influences of maternal substance use and separation on substance use problems in offspring are limited, and studies that consider both effects are rare. This study aims to review a few studies on the mechanisms, treatments, genetics, epigenetics, molecular and psychological alterations, and neuroanatomical regions involved in the dependence of offspring who underwent maternal addiction and separation. The PubMed database was used. A total of 95 articles were found, including the most related ones in the review. The brain's lateral paragigantocellularis (LPGi), nucleus accumbens (NAc), caudate-putamen (CPu), prefrontal cortex (PFC), and hippocampus, can be affected by MS. Dopamine receptor subtype genes, alcohol biomarker minor allele, and preproenkephalin mRNA may be affected by alcohol or substance use disorders. After early-life adversity, histone acetylation in the hippocampus may be linked to brain-derived neurotrophic factor (BDNF) gene epigenetics and glucocorticoid receptors (GRs). The adverse early-life experiences differ in offspring>s genders and rewire the brain>s dopamine and endocannabinoid circuits, making offspring more susceptible to dependence. Related psychological factors rooted in early-life stress (ELS) and parental substance use disorder (SUD). Treatments include antidepressants, histone deacetylase inhibitors, lamotrigine, ketamine, choline, modafinil, methadone, dopamine, cannabinoid 1 receptor agonists/antagonists, vitamins, oxytocin, tetrahydrocannabinol, SR141716A, and dronabinol. Finally, the study emphasizes the need for multifaceted strategies to prevent these outcomes.
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OBJECTIVES: This review aimed to compare the effectiveness of three treatments: BTX A, CBZ, and OXB, in managing trigeminal neuralgia (TN). MATERIAL AND METHODS: We conducted a thorough search for research articles related to our issue using specific keywords on several databases, including Cochrane Central Register of Controlled Trials, Science Direct, Scopus, PubMed, Elsevier, Springer Journals, Ovid Medline, EBSCO, and Web of Science. Our focus was on publications from 1965 to 2023. RESULTS: We retrieved 46 articles from the search and reviewed them carefully. Out of these, we selected 29 articles that met the inclusion criteria. Among the selected articles, 11 investigated the effects of CBZ and OXB, while 18 explored the impact of BTX A on the improvement of TN symptoms. The response rate ranged between 56% and 90.5% for CBZ and between 90.9% and 94% for OXB. The response rate for BTX A ranged between 51.4% and 100%. All these three treatments had a remarkable effect on the improvement of TN. Importantly, findings highlighted that side effects of CBZ and OXB could lead to treatment discontinuation in some cases, whereas BTX A's side effects have been minimal and less frequent. CONCLUSIONS: Consequently, BTX A emerges as a promising alternative for TN treatment. However, additional clinical trials are necessary to validate this finding, and further research is required to establish a standardized protocol for administering BTX A in TN.
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Toxinas Botulínicas Tipo A , Carbamazepina , Oxcarbazepina , Neuralgia del Trigémino , Neuralgia del Trigémino/tratamiento farmacológico , Humanos , Carbamazepina/uso terapéutico , Oxcarbazepina/uso terapéutico , Toxinas Botulínicas Tipo A/uso terapéutico , Toxinas Botulínicas Tipo A/administración & dosificación , Resultado del Tratamiento , Fármacos Neuromusculares/uso terapéutico , Fármacos Neuromusculares/administración & dosificación , Anticonvulsivantes/uso terapéuticoRESUMEN
Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants. Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders. The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.
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Cannabidiol , Dronabinol , Fármacos Neuroprotectores , Extractos Vegetales , Humanos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Cannabidiol/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Dronabinol/farmacología , Dronabinol/química , Dronabinol/uso terapéutico , Animales , Esclerosis Múltiple/tratamiento farmacológico , Cannabis/química , Combinación de MedicamentosRESUMEN
Recent evidence suggests the mechanistic role of mitochondria and oxidative stress in the development of celecoxib-induced cardiotoxicity. On the other, it has reported the positive effects of vitamin D on oxidative stress and the maintenance of mitochondrial functions. This current study examined the cardiac effects of celecoxib, doxorubicin, vitamin D, and a combination of them in rats. The effect of 10 days of celecoxib (100 mg/kg/day), doxorubicin (2.5 mg/kg), vitamin D (60,000 U/kg), and their combination was studied on cardiac function according to serum lactate dehydrogenase (LDH), creatine kinase (CK), glutathione (GSH), and malondialdehyde (MDA) levels as well as mitochondrial succinate dehydrogenases (SDH) activity, reactive oxygen species (ROS) production, mitochondrial swelling, and mitochondrial membrane potential (MMP). Results showed that celecoxib and its combination with doxorubicin led to abnormality in paws and limbs, increased pressure in the eyes, blindness and animal death (in about 75% of the animals under study). Moreover, celecoxib and its combination with doxorubicin significantly increased cardiotoxicity biomarkers, oxidative stress markers (GSH and MDA), and mitochondrial toxicity parameters (SDH, ROS formation, MMP collapse, mitochondrial swelling). However, the combination of vitamin D with celecoxib and celecoxib + doxorubicin caused a significant reversal of deformity in paws and limbs, increased pressure in the eye, blindness, and animal death, as well as cardiotoxicity, oxidative stress, and mitochondrial parameters. This study proved for the first time the beneficial effect of vitamin D on celecoxib-induced cardiotoxicity, which is aggravated in the presence of doxorubicin through the maintenance of mitochondrial functions and its antioxidant potential.
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Antioxidantes , Cardiotoxicidad , Celecoxib , Modelos Animales de Enfermedad , Doxorrubicina , Insuficiencia Cardíaca , Mitocondrias Cardíacas , Estrés Oxidativo , Ratas Wistar , Vitamina D , Animales , Doxorrubicina/toxicidad , Celecoxib/farmacología , Antioxidantes/farmacología , Masculino , Estrés Oxidativo/efectos de los fármacos , Cardiotoxicidad/metabolismo , Vitamina D/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Ratas , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
It is reported that tramadol can induce neurotoxic effects with the production of DNA damage, mitochondrial dysfunction, and oxidative stress. The current study aimed to evaluate the potential role of mitochondrial impairment in the pathogenesis of tramadol-induced neurotoxicity, and protective effect of sinapic acid (SA) against it in isolated mitochondria from rat brain. Mitochondria were isolated and were incubated with toxic concentrations (100 µM) of tramadol and then cotreated with tramadol + SA (10, 50, and 100 µM). Biomarkers of mitochondrial toxicity including succinate dehydrogenases (SDH) activity, reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), GSH depletion, and mitochondrial swelling were assessed. Our results showed a significant decrease in SDH activity, and a significant increase in ROS, LPO, GSH depletion, MMP collapse, and mitochondrial swelling was detected in tramadol group. We observed that 50 and 100 µM SA cotreatment for 1 h efficiently ameliorated tramadol-caused damage in mitochondrial dysfunction, accumulation of ROS, LPO, GSH depletion, depolarization of mitochondrial membrane potential, and mitochondrial swelling. These data suggest that mitochondrial impairment and oxidative stress are mechanisms involved in the pathogenesis of tramadol-induced neurotoxicity. Also, results indicate that SA antagonizes against tramadol-induced mitochondrial toxicity and suggest SA may be a preventive/therapeutic agent for tramadol-induced neurotoxicity complications.
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Ácidos Cumáricos , Enfermedades Mitocondriales , Tramadol , Ratas , Animales , Especies Reactivas de Oxígeno/metabolismo , Tramadol/toxicidad , Mitocondrias , Estrés Oxidativo , Peroxidación de Lípido , Encéfalo , Potencial de la Membrana MitocondrialRESUMEN
Trismus can be the symptom of several diseases. For the most part, the inability to open the mouth is due to an articular disorder but occasionally, the cause may be extra-articular. In this case, being reported, non-articular hysterical trismus caused the jaw to lock in an 11-year-old boy for 3 months. During this period the jaw was completely locked and the locking was associated with moderate to severe pain. After three sessions of therapy the patient was able to open his mouth 33 mm and his eating was back to normal. Conversion disorders often present with dramatic physical presentation including trismus and jaw lock. This report highlights the importance of complete history taking and a thorough clinical examination to make a correct diagnosis in a patient with trismus.
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Trastornos de Conversión , Trismo , Masculino , Humanos , Niño , Trismo/diagnóstico , Trismo/etiología , Trismo/terapia , Trastornos de Conversión/complicacionesRESUMEN
Introduction: Neuropathic pain is a common and painful somatosensory nervous system disease, and its treatment remains a medical challenge. Evidence demonstrates that gut microbiota alters in neuropathic pain and, therefore, improvement of the gut flora may affect the disease. The present study aimed to evaluate the antinociceptive effect of probiotics in neuropathic pain and oxidative biomarkers' responsiveness to the probiotic treatment. Methods: Using chronic constriction injury (CCI) of the rats' sciatic nerve, neuropathic pain was induced. Investigating the analgesic effect of the probiotics mixture, 40 male rats were randomly assigned to 4 groups (n=10 for each): Sham-operated (SM), and CCI model rats orally received 1 mL saline (CS), or 100 mg/kg gabapentin (CG) or 1 mL probiotics mixture (CP) Lactobacillus plantarum, Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Bifidobacterium bifidum (109 CFU of each) daily. Using behavioral tests, the pain was assessed on days 1, 4, 7, 14, and 21 of the study. Finally, the biochemical evaluation of sciatic nerve tissue was done. Results: Probiotics decreased cold and mechanic allodynia and thermal hyperalgesia. Reducing lipid peroxidation levels and increasing total antioxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were also significant in the probiotics group. Conclusion: These findings suggest that probiotics have analgesic effects on the CCI model of neuropathic pain via increasing the antioxidant capacity of the rats' sciatic nerve. Highlights: Oral probiotics mixture diminishes cold and mechanical allodynia in chronic constriction injury (CCI) rats.Probiotics mixture reduces thermal hyperalgesia in CCI rats as well as gabapentine.Balancing in oxidant/anti-oxidant system is key pathway in neuropathic pain reduction. Plain Language Summary: Currently, neuropathic pain is an underestimated socioeconomic health problem affecting millions of people worldwide. Neuropathic pain occurs when a health condition affects the nerves that carry sensations to the brain. With neuropathic pain, the pain isn't typically triggered by an event or injury. Instead, the body sends pain signals to the brain unprompted. Neuropathic pain tends to get worse over time. As neuropathic pain could result from an imbalance in the oxidative/antioxidative system, antioxidant supplementation may be a treatment option. Oxidative stress is known to result in the occurrence of molecular mechanisms of diabetes, atherosclerosis, inflammatory bowel disease, and damage to the heart, brain, or transplanted organs. Probiotics are made of good live bacteria and/or yeasts that naturally live in the body and have various health benefits. Consumption of probiotics alone or foods supplemented with probiotics may reduce cell oxidative damage. Incorporating probiotics in foods can provide an excellent strategy to supply dietary antioxidants. This study subjected rats to sciatic nerve ligation to induce neuropathic pain. The oral probiotics mixture was administered for 21 days post-surgery. The result showed that the probiotics mixture administration could reduce oxidative stress and pain in neuropathic pain rats. Therefore, probiotics can prevent and treat many systemic diseases in animal and human studies.
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Symptoms of temporomandibular disorders (TMD) could be present as otologic symptoms like earache and dizziness in some patients. In most cases, these symptoms are not recognized because otolaryngologists fail to diagnose TMD as a source of the problem. This investigation was conducted to evaluate the effect of TMD treatments on the otologic symptoms which after taking history and clinical examinations seemed to be related to TMD. In the present study, the patients who were complaining of otalgia, ear fullness, tinnitus, hearing loss, and dizziness were evaluated by an ear fellow. Forty patients who had no known otologic or other primary causes to explain their symptoms, were referred to the orofacial pain clinic with the possible diagnosis of TMD. If the diagnosis was confirmed by an orofacial pain specialist, a combination of TMD treatments was administered to each case and the patients were followed up. The results showed that following implementation of treatment protocols for TMD, more than 50% of the patients reported complete or partial recovery in the second follow-up (p < 0.05). The most common otologic symptom of the referred cases was earache, and the most common associated complaint was neck pain. All the patients had one or more parafunctional habits. This study showed that TMD treatments were significantly efficient in improving otologic symptoms partially or completely and the authors concluded that for the patients with otolaryngologic unexplained symptoms, an overhaul examination is needed to assess TMD as a possible cause of the patient complaint. It is recommended that in cases with unexplained otologic symptoms, otolaryngologists care more about the neck trigger points (TP) and ask about the patient's parafunctional habits. Otolaryngologists and dentists need to be aware of the risk of developing otologic symptoms caused by these habits or cervical TPs.
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Enfermedades del Oído , Trastornos de la Articulación Temporomandibular , Acúfeno , Humanos , Enfermedades del Oído/diagnóstico , Enfermedades del Oído/etiología , Enfermedades del Oído/terapia , Dolor de Oído/etiología , Dolor de Oído/terapia , Mareo/complicaciones , Acúfeno/complicaciones , Vértigo/complicaciones , Trastornos de la Articulación Temporomandibular/terapia , Trastornos de la Articulación Temporomandibular/complicaciones , Dolor Facial/etiología , Dolor Facial/terapiaRESUMEN
Prenatal stress (PS) results from a maternal experience of stressful events during pregnancy, which has been associated with an increased risk of behavioral disorders including substance abuse and anxiety in the offspring. PS is known to result in heightened dopamine release in the ventral tegmental area (VTA), in part through the effects of corticotropin-releasing hormone, which directly excites dopaminergic cells. It has recently been suggested that agmatine plays a role in modulating anxiety-like behaviors. In this study, we investigated whether agmatine could reduce negative cognitive outcomes in male mice prenatally exposed to psychological/physical stress, and whether this could be associated with molecular changes in VTA. Agmatine (37.5 mg/kg) was administrated 30 min prior to PS induction in pregnant Swiss mice. Male offspring were evaluated in a series of behavioral and molecular assays. Findings demonstrated that agmatine reduced the impairment in locomotor activity induced by both psychological and physical PS. Agmatine also decreased heightened conditioned place preference to morphine seen in PS offspring. Moreover, agmatine ameliorated the anxiety-like behavior and drug-seeking behavior induced by PS in the male offspring. Molecular effects were seen in VTA as the enhanced brain-derived neurotrophic factor (BDNF) induced by PS in the VTA was reduced by agmatine. Behavioral tests indicate that agmatine exerts a protective effect on PS-induced impairments in male offspring, which could be due in part to agmatine-associated molecular alterations in the VTA. Taken together, our data suggest that prenatal treatment with agmatine exerts protective effect against negative consequences of PS on the development of affective circuits in the offspring.
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Agmatina , Área Tegmental Ventral , Masculino , Femenino , Embarazo , Animales , Ratones , Agmatina/farmacología , Ansiedad , Trastornos de Ansiedad , CogniciónRESUMEN
Parkinson's disease (PD) is characterized by a myriad of symptoms, encompassing both motor disabilities and cognitive impairments. Recent research has shown that abscisic acid (ABA) is a phytohormone found in various brain regions of several mammals and exhibits neuroprotective properties. To investigate the effects of ABA on cognitive and motor disorders, a mouse model of PD was utilized. The administration of 6-hydroxydopamine (6-OHDA) to the lateral ventricles was conducted, with ABA (10 and 15 µg/mouse, i. c.v.) being administered for one week after the 6-OHDA injection for 4 days. Motor and cognitive performance were evaluated through the use of open field, rotarod, wire grip, and shuttle box tests. The results indicated that cognitive function and motor disorders were significantly impaired in 6-OHDA-treated animals. However, in mice treated with 6-OHDA, ABA (15 µg/mouse) significantly reversed balance and muscle strength deficits. It should be noted that the administration of ABA did not significantly improve cognitive impairment or rearing in Parkinsonism mice. Therefore, the findings suggest that ABA plays a crucial role in protecting mice from motor disabilities caused by 6-OHDA.
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Aging causes substantial molecular to morphological changes in the brain. The brain cells are more susceptible towards oxidative damage due to impaired antioxidant defense system. Sirtuin1 (SIRT1) is a crucial cellular survival protein, which its gene has been identified as a direct target of microRNA 132 (miR-132). Trehalose contributes to preventing neuronal damage through several mechanisms. However, little is known about the interactive effects of aging and trehalose on the expression pattern of miR-132 and SIRT1 in the hippocampus. Male Wistar rats were divided into four groups. Two groups of aged (24 months) and young (4 months) rats were administered 2% trehalose solution for 30 days. Two other groups of aged and young rats received regular tap water. At the end of treatment, the levels of Sirt1 mRNA and its protein, malondialdehyde, protein carbonyl content, total antioxidant capacity, tumor necrosis factor α (TNF-α), as well as the expression of miR-132 were measured in the hippocampus. We found that trehalose treatment upregulated the expression of SIRT1 and miR-132. Moreover, administration of trehalose enhanced the level of total antioxidant activity whereas reduced the levels of lipid peroxidation, protein carbonyl content, and TNF-α. In conclusion, our data indicated that trehalose restored antioxidant status and alleviated inflammation in the hippocampus which was probably associated with the upregulation of SIRT1 and miR-132.
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MicroARNs , Sirtuina 1 , Ratas , Masculino , Animales , Sirtuina 1/metabolismo , Antioxidantes/farmacología , MicroARNs/metabolismo , Trehalosa/farmacología , Trehalosa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Carbonilación Proteica , Ratas Wistar , Hipocampo/metabolismoRESUMEN
Maternal morphine exposure has negative consequences for learning and memory in the offspring. Interaction between mothers and pups has a crucial effect on the mammal's development. Maternal Separation (MS) can cause behavioral and neuropsychiatric problems later in life. It seems that adolescents are more susceptible to the effects of early life stress; evidence for the combinatory effects of oral chronic maternal morphine exposure and MS in the CA1 area of the hippocampus in the male adolescent offspring is not found. Therefore, this study aimed to evaluate the effects of chronic maternal morphine consumption (21 days before and after mating, and gestation), and MS (180 min/day from postnatal day (PND) 1-21) on the synaptic plasticity of male offspring in mid-adolescence. Control, MS, Vehicle (V), Morphine, V + MS, and Morphine + MS groups were tested for in vivo field potential recording from the CA1 area of the hippocampus. The current results demonstrated that chronic maternal morphine exposure impaired the induction of early long-term potentiation (LTP). MS impaired average fEPSPs, induction of early-LTP and maintenance. Chronic maternal morphine exposure in combination with MS impaired the induction of early LTP but didn't deteriorate maintenance and the average field excitatory post-synaptic potentials (fEPSPs) measured in two hours. Prepulse facilitation ratios remained undisturbed and I/O curves showed decreased fEPSP slopes at high stimulus intensities in combinatory group. We concluded that chronic maternal morphine exposure in combination with MS negatively affects synaptic plasticity in the CA1 area in male adolescent offspring.
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Morfina , Estrés Psicológico , Animales , Masculino , Ratas , Hipocampo , Potenciación a Largo Plazo , Mamíferos , Privación Materna , Morfina/efectos adversos , Plasticidad NeuronalRESUMEN
Over-expression of K+ channels has been reported in human cancers and is associated with the poor prognosis of several malignancies. EAG1, a particular potassium ion channel, is widely expressed in the brain but poorly expressed in other normal tissues. Kunitz proteins are dominant in metazoan including the dog tapeworm, Echinococcus granulosus. Using computational analyses on one A-type potassium channel, EAG1, and in vitro cellular methods, including major cancer cell biomarkers expression, immunocytochemistry and whole-cell patch clamp, we demonstrated the anti-tumor activity of three synthetic small peptides derived from E. granulosus Kunitz4 protease inhibitors. Experiments showed induced significant apoptosis and inhibition of proliferation in both cancer cell lines via disruption in cell-cycle transition from the G0/G1 to S phase. Western blotting showed that the levels of cell cycle-related proteins including P27 and P53 were altered upon kunitz4-a and kunitz4-c treatment. Patch clamp analysis demonstrated a significant increase in spontaneous firing frequency in Purkinje neurons, and exposure to kunitz4-c was associated with an increase in the number of rebound action potentials after hyperpolarized current. This noteworthy component in nature could act as an ion channel blocker and is a potential candidate for cancer chemotherapy based on potassium channel blockage.
Asunto(s)
Infecciones por Cestodos , Echinococcus granulosus , Neoplasias , Perros , Animales , Humanos , Echinococcus granulosus/metabolismo , Neoplasias/tratamiento farmacológico , Inhibidores de Proteasas/metabolismo , Péptidos/metabolismo , Canales de Potasio/metabolismoRESUMEN
Temozolomide is used commonly in the treatment of some types of cancers, but it may also result in cognitive impairments such as memory deficits. l -Dopa, a well known medicine for the central nervous system, has been shown to have positive effects on some cognitive disorders. Here we sought to investigate the effect of l -Dopa on temozolomide-induced cognitive impairments. BALB/c mice were subjected to 3-days temozolomide and 6-days concomitant l -Dopa/benserazide administration in six groups (control, l -Dopa 25â mg/kg, l -Dopa 75â mg/kg, temozolomide, temozolomideâ +â l -Dopa 25â mg/kg, and temozolomideâ +â l -Dopa 75â mg/kg). Open field test, object location recognition, novel object recognition test, and shuttle-box test were carried out to determine the locomotor, anxiety-like behavior, and memory function of subjects. TNF-α and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus was measured by real-time PCR. Mice treated with temozolomide showed recognition memory impairment, along with hippocampal TNF-α and BDNF mRNA expression level raise, and detection of histological insults in hematoxylin and eosin hippocampal slides. Mice that received temozolomideâ +â l -Dopa showed normal behavioral function and lower TNF-α and BDNF hippocampal mRNA expression levels, and histologically normal hippocampal CA1 region in comparison with mice in the temozolomide group. Our results provide evidence that l -Dopa prevents temozolomide-induced recognition memory deficit in mice at the acute phase probably via l -Dopa antineuroinflammatory effects.