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INTRODUCTION: Tissue injury results in the release of inflammatory mediators, including a cascade of algogenic substances, which contribute to the development of hyperalgesia. During this process, endogenous analgesic substances are peripherally released to counterbalance hyperalgesia. The present study aimed to investigate whether inflammatory mediators TNF-α, IL-1ß, CXCL1, norepinephrine (NE), and prostaglandin E2 (PGE2) may be involved in the deflagration of peripheral endogenous modulation of inflammatory pain by activation of the cholinergic system. METHODS: Male Swiss mice were subjected to paw withdrawal test. All the substances were injected via the intraplantar route. RESULTS: The main findings of this study were as follows: (1) carrageenan (Cg), TNF-α, CXCL-1, IL1-ß, NE, and PGE2 induced hyperalgesia; (2) the acetylcholinesterase enzyme inhibitor, neostigmine, reversed the hyperalgesia observed after Cg, TNF-α, CXCL-1, and IL1-ß injection; (3) the non-selective muscarinic receptor antagonist, atropine, and the selective muscarinic type 1 receptor (m1AChr) antagonist, telenzepine, potentiated the hyperalgesia induced by Cg and CXCL-1; (4) mecamylamine, a non-selective nicotinic receptor antagonist, potentiated the hyperalgesia induced by Cg, TNF-α, CXCL-1, and IL1-ß; (5) Cg, CXCL-1, and PGE2 increased the expression of the m1AChr and nicotinic receptor subunit α4protein. CONCLUSION: These results suggest that the cholinergic system may modulate the inflammatory pain induced by Cg, PGE2, TNF-α, CXCL-1, and IL1-ß.
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In the retrosplenial cortex (RSC), the role of cholinergic modulation via α7 nicotinic receptors and their involvement in memory is unknown. In recent years, the RSC has been shown to deteriorate in the early stages of Alzheimer's disease (AD). Likewise, the cholinergic system has been postulated as one of those responsible for cognitive impairment in patients with AD. Great interest has arisen in the study of α7 nicotinic receptors as more specific targets for the treatment of this disease. For this reason, we aim to study the role of α7 receptors of the RSC in memory processing. We infused a selective α7 receptor antagonist into the anterior part of the RSC (aRSC) to assess its role in different phases of aversive memory processing using an inhibitory avoidance task. We found that α7 nicotinic receptors are involved in memory acquisition and expression, but not in its consolidation. These results identify aRSC α7 nicotinic receptors as key players in aversive memory processing and highlight their significant potential as therapeutic targets for Alzheimer's disease.
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In spite of the vaccine development and its importance, the SARS-CoV-2 pandemic is still impacting the world. It is known that the COVID-19 severity is related to the cytokine storm phenomenon, being inflammation a common disease feature. The nicotinic cholinergic system has been widely associated with COVID-19 since it plays a protective role in inflammation via nicotinic receptor alpha 7 (nAchRalpha7). In addition, SARS-CoV-2 spike protein (Spro) subunits can interact with nAchRalpha7. Moreover, Spro causes toll-like receptor (TLR) activation, leading to pro- and anti-inflammatory pathways. The increase and maturation of the IL-1 receptor-associated kinase (IRAK) family are mediated by activation of membrane receptors, such as TLRs. IRAK-M, a member of this family, is responsible for negatively regulating the activity of other active IRAKs. In addition, IRAK-M can regulate microglia phenotype by specific protein expression. Furthermore, there exists an antagonist influence of SARS-CoV-2 Spro and the cholinergic system action on the IRAK-M pathway and microglia phenotype. We discuss the overexpression and suppression of IRAK-M in inflammatory cell response to inflammation in SARS-CoV-2 infection when the cholinergic system is constantly activated via nAchRalpha7.
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COVID-19 , Transdução de Sinais , Glicoproteína da Espícula de Coronavírus , Humanos , Transdução de Sinais/genética , Quinases Associadas a Receptores de Interleucina-1/metabolismo , SARS-CoV-2 , Inflamação , ColinérgicosRESUMO
Maple Syrup Urine Disease (MSUD) is a metabolic disease characterized by the accumulation of branched-chain amino acids (BCAA) in different tissues due to a deficit in the branched-chain alpha-ketoacid dehydrogenase complex. The most common symptoms are poor feeding, psychomotor delay, and neurological damage. However, dietary therapy is not effective. Studies have demonstrated that memantine improves neurological damage in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Therefore, we hypothesize that memantine, an NMDA receptor antagonist can ameliorate the effects elicited by BCAA in an MSUD animal model. For this, we organized the rats into four groups: control group (1), MSUD group (2), memantine group (3), and MSUD + memantine group (4). Animals were exposed to the MSUD model by the administration of BCAA (15.8 µL/g) (groups 2 and 4) or saline solution (0.9%) (groups 1 and 3) and treated with water or memantine (5 mg/kg) (groups 3 and 4). Our results showed that BCAA administration induced memory alterations, and changes in the levels of acetylcholine in the cerebral cortex. Furthermore, induction of oxidative damage and alterations in antioxidant enzyme activities along with an increase in pro-inflammatory cytokines were verified in the cerebral cortex. Thus, memantine treatment prevented the alterations in memory, acetylcholinesterase activity, 2',7'-Dichlorofluorescein oxidation, thiobarbituric acid reactive substances levels, sulfhydryl content, and inflammation. These findings suggest that memantine can improve the pathomechanisms observed in the MSUD model, and may improve oxidative stress, inflammation, and behavior alterations.
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Doença da Urina de Xarope de Bordo , Ratos , Animais , Doença da Urina de Xarope de Bordo/tratamento farmacológico , Doença da Urina de Xarope de Bordo/metabolismo , Memantina/farmacologia , Memantina/uso terapêutico , Acetilcolinesterase , Modelos Animais de Doenças , Aminoácidos de Cadeia Ramificada , Antioxidantes/farmacologia , InflamaçãoRESUMO
Aspartame (ASP) is a common sweetener, but studies show it can harm the nervous system, causing learning and memory deficits. ß-caryophyllene (BCP), a natural compound found in foods, including bread, coffee, alcoholic beverages, and spices, has already described as a neuroprotector agent. Remarkably, ASP and BCP are commonly consumed, including in the same meal. Therefore, considering that (a) the BCP displays plenty of beneficial effects; (b) the ASP toxicity; and (c) that they can be consumed in the same meal, this study sought to investigate if the BCP would mitigate the memory impairment induced by ASP in rats and investigate the involvement of the brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrKB) signaling pathway and acetylcholinesterase (AChE) activity. Young male Wistar rats received ASP (75 mg/kg; i.g.) and/or BCP (100 mg/kg; i.p.) once daily, for 14 days. At the end of the treatment, the animals were evaluated in the open field and object recognition tests. The cerebral cortex and hippocampus samples were collected for biochemical and molecular analyses. Results showed that the BCP effectively protected against the cognitive damage caused by ASP in short and long-term memories. In addition, BCP mitigated the increase in AChE activity caused by ASP. Molecular insights revealed augmented BDNF and TrKB levels in the hippocampus of rats treated with BCP, indicating greater activation of this pathway. In conclusion, BCP protected against ASP-induced memory impairment. AChE activity and the BDNF/TrkB signaling pathway seem to be potential targets of BCP modulatory role in this study.
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Acetilcolinesterase , Disfunção Cognitiva , Animais , Masculino , Ratos , Acetilcolinesterase/metabolismo , Aspartame/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/prevenção & controle , Ratos Wistar , Receptor trkB/metabolismo , Transdução de Sinais , Tropomiosina/metabolismoRESUMO
Glaucoma is a common cause of visual loss and irreversible blindness, affecting visual and life quality. Various mechanisms are involved in retinal ganglion cell (RGC) apoptosis and functional and structural loss in the visual system. The prevalence of glaucoma has increased in several countries. However, its early diagnosis has contributed to prompt attention. Molecular and cellular biological mechanisms are important for understanding the pathological process of glaucoma and new therapies. Thus, this review discusses the factors involved in glaucoma, from basic science to cellular and molecular events (e.g., mitochondrial dysfunction, endoplasmic reticulum stress, glutamate excitotoxicity, the cholinergic system, and genetic and epigenetic factors), which in recent years have been included in the development of new therapies, management, and diagnosis of this disease.
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Glaucoma , Humanos , Glaucoma/genética , Células Ganglionares da Retina/patologiaRESUMO
Alzheimer's disease (AD) is of multifactorial origin, and still presents several gaps regarding its development and progression. Disorders of the cholinergic system are well known to be involved in the pathogenesis of AD, characterized by increased acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and decreased acetyltransferase (ChAT) enzymatic activities. Late onset AD (LOAD) animal model induced by intracerebroventricular injection of streptozotocin (icv-STZ) showed promising results in this context, due to the similarity with the pathophysiology of human LOAD. Thus, this study aimed to assess the long-term effects of icv-STZ on the cholinergic system, through the measuring of AChE and BChE enzymatic activities in hippocampus, prefrontal cortex and liver of animals euthanized 30 and 120-days after the icv-STZ. Regarding the cholinergic response to icv-STZ, the 30-days and 120-days STZ-induced rats exhibit decreased AChE and BChE activities only in the hippocampus. The cognitive deficit was more consistent in the 30-days post icv-STZ animals, as was the weight loss. This is the first study to investigate the long-term effects (more than 60 days) of the icv-STZ on AChE and BChE activities, and our results, as well as those of a recent study, suggest that the cholinergic system may not be compromised by icv-STZ, at least in the long term, which means that this model may not be the best model for studying the cholinergic system in AD or that it is informative only for a short period.
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Doença de Alzheimer , Fármacos Neuroprotetores , Ratos , Humanos , Animais , Doença de Alzheimer/metabolismo , Estreptozocina/farmacologia , Ratos Wistar , Acetilcolinesterase/metabolismo , Butirilcolinesterase , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Colinérgicos/farmacologia , Aprendizagem em LabirintoRESUMO
The presence of insoluble aggregates of amyloid ß (Aß) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer's disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aß peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each presenting different levels of toxicity. Aß peptides can be internalized by particular receptors and trigger changes from Tau phosphorylation to alterations in cognitive function, through dysfunction of the cholinergic system. The goal of this review is to summarize the current knowledge on the role of lipids in Alzheimer's disease and their relationship with the basal cholinergic system, as well as potential disease-modifying therapies.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Metabolismo dos Lipídeos , Metabolismo Basal , Fragmentos de Peptídeos/metabolismo , Colinérgicos , LipídeosRESUMO
Organophosphorus pesticides (OPs) are widespread insecticides used for pest control in agricultural activities and the control of the vectors of human and animal diseases. However, OPs' neurotoxic mechanism involves cholinergic components, which, beyond being involved in the transmission of neuronal signals, also influence the activity of cytokines and other pro-inflammatory molecules; thus, acute and chronic exposure to OPs may be related to the development of chronic degenerative pathologies and other inflammatory diseases. The present article reviews and discusses the experimental evidence linking inflammatory process with OP-induced cholinergic dysregulation, emphasizing the molecular mechanisms related to the role of cytokines and cellular alterations in humans and other animal models, and possible therapeutic targets to inhibit inflammation.
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Praguicidas , Animais , Colinérgicos , Citocinas , Inflamação , Compostos Organofosforados/toxicidade , Praguicidas/toxicidadeRESUMO
Lung inflammation is modulated by cholinergic signaling and exercise training protects mice against pulmonary emphysema development; however, whether exercise training engages cholinergic signaling is unknown. AIMS: As cholinergic signaling is directly linked to the vesicular acetylcholine transporter (VAChT) levels, we evaluated whether the effects of aerobic exercise training depend on the VAChT levels in mice with pulmonary emphysema. MAIN METHODS: Wild-type (WT) and mutant (KDHOM) mice (65-70% of reduction in VAChT levels) were exposed to cigarette smoke (30 min, 2×/day, 5×/week, 12 weeks) and submitted or not to aerobic exercise training on a treadmill (60 min/day, 5×/week, 12 weeks). Lung function and inflammation were evaluated. KEY FINDINGS: Cigarette smoke reduced body mass in mice (p < 0.001) and increased alveolar diameter (p < 0.001), inflammation (p < 0.001) and collagen deposition (p < 0.01) in lung tissue. Both trained groups improved their performance in the final physical test compared to the initial test (p < 0.001). In WT mice, exercise training protected against emphysema development (p < 0.05), reduced mononuclear cells infiltrate (p < 0.001) and increased MAC-2 positive cells in lung parenchyma (p < 0.05); however, these effects were not observed in KDHOM mice. The exercise training reduced iNOS-positive cells (p < 0.001) and collagen fibers deposition (p < 0.05) in lung parenchyma of WT and KDHOM mice, although KDHOM mice showed higher levels of iNOS-positive cells. SIGNIFICANCE: Our data suggest that the protective effects of aerobic exercise training on pulmonary emphysema are, at least in part, dependent on the integrity of the lung cholinergic signaling.
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Fumar Cigarros , Enfisema , Enfisema Pulmonar , Animais , Colinérgicos , Inflamação , Pulmão , Camundongos , Camundongos Endogâmicos C57BL , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/prevenção & controle , Proteínas Vesiculares de Transporte de AcetilcolinaRESUMO
Fluoride is an essential chemical found in dental preparations, pesticides and drinking water. Excessive fluoride exposure is related to toxicological and neurological disruption. Zebrafish are used in translational approaches to understand neurotoxicity in both biomedical and environmental areas. However, there is no complete knowledge about the cumulative effects of fluoride on neurotransmission systems. Therefore, the aim of this study was to evaluate whether prolonged exposure to sodium fluoride (NaF) alters cholinergic and glutamatergic systems and oxidative stress homeostasis in the zebrafish brain. Adult zebrafish were used, divided into four experimental groups, one control group and three groups exposed to NaF at 30, 50 and 100 mg.L-1 for a period of 30 days. After NaF at 30 mg.L-1 exposure, there were significant decreases in acetylcholinesterase (29.8 %) and glutamate uptake (39.3 %). Furthermore, thiobarbituric acid-reactive species were decreased at NaF 50 mg.L-1 (32.7 %), while the group treated with NaF at 30 mg.L-1 showed an increase in dichlorodihydrofluorescein oxidation (41.4 %). NaF at 30 mg.L-1 decreased both superoxide dismutase (55.3 %) and catalase activities (26.1 %). The inhibitory effect observed on cholinergic and glutamatergic signalling mechanisms could contribute to the neurodegenerative events promoted by NaF in the zebrafish brain.
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Encéfalo , Fluoretos , Estresse Oxidativo , Transmissão Sináptica , Peixe-Zebra , Acetilcolinesterase/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Fluoretos/efeitos adversos , Transmissão Sináptica/efeitos dos fármacos , Peixe-Zebra/metabolismoRESUMO
AIM: The aim of this study was to assess the influence of adrenomedullary secretion on the plasma glucose, lactate, and free fatty acids (FFAs) during running exercise in rats submitted to intracerebroventricular (i.c.v.) injection of physostigmine (PHY). PHY i.c.v. was used to activate the central cholinergic system. METHODS: Wistar rats were divided into sham-saline (sham-SAL), sham-PHY, adrenal medullectomy-SAL, and ADM-PHY groups. The plasma concentrations of glucose, lactate, and FFAs were determined immediately before and after i.c.v. injection of 20 µL of SAL or PHY at rest and during running exercise on a treadmill. RESULTS: The i.c.v. injection of PHY at rest increased plasma glucose in the sham group, but not in the ADM group. An increase in plasma glucose, lactate, and FFAs mobilization from adipose tissue was observed during physical exercise in the sham-SAL group; however, the increase in plasma glucose was greater with i.c.v. PHY. Moreover, the hyperglycemia induced by exercise and PHY in the ADM group were blunted by ADM, whereas FFA mobilization was unaffected. CONCLUSION: These results indicate that there is a dual metabolic control by which activation of the central cholinergic pathway increases plasma glucose but not FFA during rest and exercise, and that this hyperglycemic response is dependent on adrenomedullary secretion.
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Medula Suprarrenal/fisiologia , Fibras Colinérgicas/fisiologia , Metabolismo/fisiologia , Esforço Físico/fisiologia , Medula Suprarrenal/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Fibras Colinérgicas/efeitos dos fármacos , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/farmacologia , Ácidos Graxos não Esterificados/sangue , Injeções Intraventriculares , Ácido Láctico/sangue , Masculino , Metabolismo/efeitos dos fármacos , Condicionamento Físico Animal , Fisostigmina/administração & dosagem , Fisostigmina/farmacologia , Ratos WistarRESUMO
AIMS: Homocysteine has been linked to neurodegeneration and motor function impairments. In the present study, we evaluate the effect of chronic mild hyperhomocysteinemia on the motor behavior (motor coordination, functional performance, and muscular force) and biochemical parameters (oxidative stress, energy metabolism, gene expression and/or protein abundance of cytokine related to the inflammatory pathways and acetylcholinesterase) in the striatum and cerebellum of Wistar male rats. MAIN METHODS: Rodents were submitted to one injection of homocysteine (0.03 µmol Hcy/g of body weight) between 30th and 60th postnatal days twice a day. After hyperhomocysteinemia induction, rats were submitted to horizontal ladder walking, beam balance, suspension, and vertical pole tests and/or euthanized to brain dissection for biochemical and molecular assays. KEY FINDINGS: Chronic mild hyperhomocysteinemia did not alter motor function, but induced oxidative stress and impaired mitochondrial complex IV activity in both structures. In the striatum, hyperhomocysteinemia decreased TNF-α gene expression and increased IL-1ß gene expression and acetylcholinesterase activity. In the cerebellum, hyperhomocysteinemia increased gene expression of TNF-α, IL-1ß, IL-10, and TGF-ß, while the acetylcholinesterase activity was decreased. In both structures, hyperhomocysteinemia decreased acetylcholinesterase protein abundance without altering total p-NF-κB, NF-κB, Nrf-2, and cleaved caspase-3. SIGNIFICANCE: Chronic mild hyperhomocysteinemia compromises several biochemical/molecular parameters, signaling pathways, oxidative stress, and chronic inflammation in the striatum and cerebellum of rats without impairing motor function. These alterations may be related to the mechanisms in which hyperhomocysteinemia has been linked to movement disorders later in life and neurodegeneration.
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Cerebelo/patologia , Corpo Estriado/patologia , Citocinas/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Hiper-Homocisteinemia/fisiopatologia , Estresse Oxidativo , Animais , Cerebelo/metabolismo , Corpo Estriado/metabolismo , Citocinas/genética , Metabolismo Energético , Regulação da Expressão Gênica , Homocisteína/metabolismo , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Ratos , Ratos WistarRESUMO
Gallic acid (GA) is a polyphenolic compound that has attracted significant interest due to its antioxidant action through free radical elimination and metal chelation. Ethanol is a highly soluble psychoactive substance, and its toxicity is associated with oxidative stress. In this context, the purpose of the present study was to investigate the effect of GA on neurochemical changes in zebrafish brains exposed to ethanol. GA was first analyzed in isolation by treating the animals at concentrations of 5, 10, and 20â¯mg/L for 24â¯h and 48â¯h. The results revealed that the group exposed to 20â¯mg/L over a 24/48â¯h period exhibited increases in thiobarbituric acid reactive substance (TBA-RS) levels and 2',7'-dichlorofluorescein (DCFH) oxidation, demonstrating a pro-oxidant profile. Moreover, decrease in acetylcholinesterase (AChE) enzyme activity was observed. To investigate the effects of GA after ethanol exposure, the animals were divided into four groups: control; those exposed to 0.5% ethanol for 7â¯days; those exposed to 0.5% ethanol for 7â¯days and treated with GA at 5 and 10â¯mg/L on day 8. Treatment with GA at 5 and 10â¯mg/L reversed impairment of choline acetyltransferase activity and the damage to TBA-RS levels, DCFH oxidation, and superoxide dismutase activity induced by ethanol. Results of the present study suggest that GA treatment (20â¯mg/L) appeared to disrupt oxidative parameters in the zebrafish brain. GA treatment at 5 and 10â¯mg/L reversed alterations to the cholinergic system induced by prolonged exposure to ethanol in the zebrafish brain, probably through an antioxidant mechanism.
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Encéfalo , Etanol , Ácido Gálico , Animais , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Etanol/toxicidade , Ácido Gálico/farmacologia , Estresse Oxidativo , Peixe-ZebraRESUMO
BACKGROUND: Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disease. Recent studies have reported the close association between cognitive function in AD and purinergic receptors in the central nervous system. In the current study, we investigated the effect of CD73 inhibitor α, ß-methylene ADP (APCP) on cognitive impairment of AD in mice, and to explore the potential underlying mechanisms. RESULTS: We found that acute administration of Aß142 (i.c.v.) resulted in a significant increase in adenosine release by using microdialysis study. Chronic administration of APCP (10, 30 mg/kg) for 20 d obviously mitigated the spatial working memory impairment of Aß142-treated mice in both Morris water maze (MWM) test and Y-maze test. In addition, the extracellular adenosine production in the hippocampus was inhibited by APCP in Aß-treated mice. Further analyses indicated expression of acetyltransferase (ChAT) in hippocampus of mice of was significantly reduced, while acetylcholinesterase (AChE) expression increased, which compared to model group. We observed that APCP did not significantly alter the NLRP3 inflammasome activity in hippocampus, indicating that anti-central inflammation seems not to be involved in APCP effect. CONCLUSIONS: In conclusion, we report for the first time that inhibition of CD73 by APCP was able to protect against memory loss induced by Aß142 in mice, which may be due to the decrease of CD73-driven adenosine production in hippocampus. Enhancement of central cholinergic function of the central nervous system may also be involved in the effects of APCP.
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Animais , Masculino , Camundongos , Difosfato de Adenosina/análogos & derivados , Doenças Neurodegenerativas/prevenção & controle , Hipocampo , Nucleotidases/antagonistas & inibidores , Acetilcolinesterase , Difosfato de Adenosina/administração & dosagem , Doença de Alzheimer/prevenção & controle , Teste do Labirinto Aquático de Morris , Camundongos Endogâmicos C57BLRESUMO
Pesticide exposure is associated with cognitive and psychomotor disorders. Glyphosate-based herbicides (GlyBH) are among the most used agrochemicals, and inhalation of GlyBH sprays may arise from frequent aerial pulverizations. Previously, we described that intranasal (IN) administration of GlyBH in mice decreases locomotor activity, increases anxiety, and impairs recognition memory. Then, the aim of the present study was to investigate the mechanisms involved in GlyBH neurotoxicity after IN administration. Adult male CF-1 mice were exposed to GlyBH IN administration (equivalent to 50 mg/kg/day of Gly acid, 3 days a week, during 4 weeks). Total thiol content and the activity of the enzymes catalase, acetylcholinesterase and transaminases were evaluated in different brain areas. In addition, markers of the cholinergic and the nigrostriatal pathways, as well as of astrocytes were evaluated by fluorescence microscopy in coronal brain sections. The brain areas chosen for analysis were those seen to be affected in our previous study. GlyBH IN administration impaired the redox balance of the brain and modified the activities of enzymes involved in cholinergic and glutamatergic pathways. Moreover, GlyBH treatment decreased the number of cholinergic neurons in the medial septum as well as the expression of the α7-acetylcholine receptor in the hippocampus. Also, the number of astrocytes increased in the anterior olfactory nucleus of the exposed mice. Taken together, these disturbances may contribute to the neurobehavioural impairments reported previously by us after IN GlyBH administration in mice.
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Acetilcolina/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Glicina/análogos & derivados , Herbicidas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Administração Intranasal , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Glicina/administração & dosagem , Glicina/toxicidade , Herbicidas/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Bulbo Olfatório/efeitos dos fármacos , Bulbo Olfatório/metabolismo , Oxirredução , Núcleos Septais/efeitos dos fármacos , Núcleos Septais/metabolismo , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Compostos de Sulfidrila/metabolismo , Transaminases/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , GlifosatoRESUMO
Maple Syrup Urine Disease (MSUD) is an autosomal recessive inherited disorder, caused by a deficiency on branched chain α-ketoacid dehydrogenase complex activity, resulting in accumulation of branched-chain amino acids (BCAA) (e.g. leucine). The treatment of MSDU patients increases survival time and quality of life. Thus, nowadays there are a crescent number of adolescents and adults with MSUD. Relevant studies have been reported behavioral alterations in these patients, i.e. high risk of chronic neuropsychiatric problems, such as attention deficit disorder, depression and anxiety. Moreover, MSUD is associated to neurotransmitters deficiency. Herein, we aimed to investigate whether the toxicity of leucine is associated to anxiety-like behavioral, using zebrafish acutely exposed to leucine as experimental model of MSUD. In addition, we evaluated the effects of high levels of leucine in the acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities, components of cholinergic neurotransmission system. Young zebrafish were exposed to 2â¯mM and 5â¯mM concentration of leucine for 24â¯h. After that, the animals were submitted to the Novel Tank test, having the brain collected to enzymatic determination. The exposure to both concentrations of leucine caused behavioral and brain cholinergic activity alterations in young zebrafish, indicating an anxiety-like behavior and cholinergic dysfunction. Therefore, this animal could be considered a promising organism to study the BCAA neurotoxic effects, which could help to a better comprehension of the behavioral and neurochemical alterations present in patients with MSUD.
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Acetilcolinesterase/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Colina O-Acetiltransferase/metabolismo , Leucina/farmacologia , Doença da Urina de Xarope de Bordo/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Peixe-ZebraRESUMO
The expression of elements of the cholinergic system has been demonstrated in non-neuronal cells, such as immune cells, where acetylcholine modulates innate and adaptive responses. However, the study of the non-neuronal cholinergic system has focused on lymphocyte cholinergic mechanisms, with less attention to its role of innate cells. Considering this background, the aims of this review are 1) to review information regarding the cholinergic components of innate immune system cells; 2) to discuss the effect of cholinergic stimuli on cell functions; 3) and to describe the importance of cholinergic stimuli on host immunocompetence, in order to set the base for the design of intervention strategies in the biomedical field.
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Acetilcolina/imunologia , Imunidade Inata/imunologia , Leucócitos/imunologia , Animais , HumanosRESUMO
Nervous and immune systems maintain a bidirectional communication, expressing receptors for neurotransmitters and cytokines. Despite being well established in mammals, this has been poorly described in lower vertebrates as fishes. Experimental evidence shows that the neurotransmitter acetylcholine (ACh) regulates the immune response. In this research, we evaluated mRNA levels of muscarinic acetylcholine receptor (mAChR) in spleen mononuclear cells of Nile tilapia (Oreochromis niloticus) and compared the expression levels of immune cells with the brain. The mAChR subtypes (M2-M5A) were detected in both tissues, but mAChRs mRNA levels were higher in immune cells. This data have a potential use in biomedical and comparative immunology fields.