RESUMO
PURPOSE: Some evidence that non-steroidal anti-inflammatory drugs have neuroprotective effects indicates their potential for use in a new field. However, their effects on hormone secretion have yet to be adequately discovered. Therefore, we aimed to evaluate the effects of metamizole and indomethacin on neuronal markers as well as the GnRH expression in the GT1-7 cell line. METHODS: The effects of these drugs on proliferation were evaluated by MTT analysis. The effect of 10-50-250 µM concentrations of the drugs also on the expression of neuronal factors and markers, including NGF, nestin and ßIII Tubulin, and additionally GnRH, was determined by the RT-qPCR method. RESULTS: NGF and nestin mRNA expressions were increased in all concentrations of both metamizole and indomethacin. No changes were detected in ßIII Tubulin. While metamizole showed an increase in GnRH mRNA expression, there was no change at 10 and 50 µM concentrations of indomethacin, but a remarkable decrease was observed at 250 µM concentrations. CONCLUSIONS: The results of our study showing an increase in the expression of neuronal factors reveal that metamizole and indomethacin may have possible neuroprotective effects. Moreover, the effects on the GnRH expression appear to be different. Animal models are required to confirm these effects of NSAIDs on neurons.
Assuntos
Anti-Inflamatórios não Esteroides , Dipirona , Hormônio Liberador de Gonadotropina , Indometacina , Neurônios , Indometacina/farmacologia , Hormônio Liberador de Gonadotropina/metabolismo , Dipirona/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Animais , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Linhagem Celular , Camundongos , Fármacos Neuroprotetores/farmacologia , Nestina/metabolismo , Nestina/genética , Proliferação de Células/efeitos dos fármacos , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/metabolismo , Biomarcadores/metabolismoRESUMO
Neuroactive steroids are a type of steroid hormones produced within the nervous system or in peripheral glands and then transported to the brain to exert their neuromodulatory effects. Neuroactive steroids have pleiotropic effects, that include promoting myelination, neuroplasticity, and brain development. They also regulate important physiological functions, such as metabolism, feeding, reproduction, and stress response. The homoeostatic processes of metabolism and reproduction are closely linked and mutually dependent. Reproductive events, such as pregnancy, bring about significant changes in metabolism, and metabolic status may affect reproductive function in mammals. In females, the regulation of reproduction and energy balance is controlled by the fluctuations of oestradiol and progesterone throughout the menstrual cycle. Neurosteroids play a key role in the neuroendocrine control of reproduction. The synthesis of neuroestradiol and neuroprogesterone within the brain is a crucial process that facilitates the release of GnRH and LH, which in turn, regulate the transition from oestrogen-negative to oestrogen-positive feedback. In addition to their function in the reproductive system, oestrogen has a key role in the regulation of energy homoeostasis by acting at central and peripheral levels. The oestrogenic effects on body weight homoeostasis are primarily mediated by oestrogen receptors-α (ERα), which are abundantly expressed in multiple brain regions that are implicated in the regulation of food intake, basal metabolism, thermogenesis, and brown tissue distribution. The tight interplay between energy balance and reproductive physiology is facilitated by shared regulatory pathways, namely POMC, NPY and kisspeptin neurons, which are targets of oestrogen regulation and likely participate in different aspects of the joint control of energy balance and reproductive function. The aim of this review is to present a summary of the progress made in uncovering shared regulatory pathways that facilitate the tight coupling between energy balance and reproductive physiology, as well as their reciprocal interactions and the modulation induced by neurosteroids.
Assuntos
Ingestão de Alimentos , Metabolismo Energético , Neuroesteroides , Reprodução , Humanos , Reprodução/fisiologia , Animais , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Metabolismo Energético/efeitos dos fármacos , Neuroesteroides/metabolismo , Sistemas Neurossecretores/fisiologia , Sistemas Neurossecretores/metabolismo , Sistemas Neurossecretores/efeitos dos fármacos , Feminino , Encéfalo/metabolismo , Encéfalo/fisiologiaRESUMO
Ammonia-N, as the most toxic nitrogenous waste, has high toxicity to marine animals. However, the interplay between ammonia-induced neuroendocrine toxicity and intestinal immune homeostasis has been largely overlooked. Here, a significant concordance of metabolome and transcriptome-based "cholinergic synapse" supports that plasma metabolites acetylcholine (ACh) plays an important role during NH4Cl exposure. After blocking the ACh signal transduction, the release of dopamine (DA) and 5-hydroxytryptamine (5-HT) in the cerebral ganglia increased, while the release of NPF in the thoracic ganglia and NE in the abdominal ganglia, and crustacean hyperglycemic hormone (CHH) and neuropeptide F (NPF) in the eyestalk decreased, finally the intestinal immunity was enhanced. After bilateral eyestalk ablation, the neuroendocrine system of shrimp was disturbed, more neuroendocrine factors, such as corticotropin releasing hormone (CRH), adrenocorticotropic-hormone (ACTH), ACh, DA, 5-HT, and norepinephrine (NE) were released into the plasma, and further decreased intestinal immunity. Subsequently, these neuroendocrine factors reach the intestine through endocrine or neural pathways and bind to their receptors to affect downstream signaling pathway factors to regulate intestinal immune homeostasis. Combined with different doses of ammonia-N exposure experiment, these findings suggest that NH4Cl may exert intestinal toxicity on shrimp by disrupting the cerebral ganglion-eyestalk axis and the cerebral ganglion-thoracic ganglion-abdominal ganglion axis, thereby damaging intestinal barrier function and inducing inflammatory response.
Assuntos
Amônia , Penaeidae , Animais , Penaeidae/imunologia , Penaeidae/efeitos dos fármacos , Penaeidae/metabolismo , Amônia/toxicidade , Intestinos/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Dopamina/metabolismo , Nitrogênio/metabolismo , Acetilcolina/metabolismo , Sistemas Neurossecretores/efeitos dos fármacos , Proteínas de Artrópodes/metabolismoRESUMO
BACKGROUND: Researchers have not studied the integrity, orderly correlation, and dynamic openness of complex organisms and explored the laws of systems from a global perspective. In the context of reductionism, antidepressant development formerly focused on advanced technology and molecular details, clear targets and mechanisms, but the clinical results were often unsatisfactory. PURPOSE: MDD represents an aggregate of different and highly diverse disease subtypes. The co-occurrence of stress-induced nonrandom multimorbidity is widespread, whereas only a fraction of the potential clusters are well known, such as the MDD-FGID cluster. Mapping these clusters, and determining which are nonrandom, is vital for discovering new mechanisms, developing treatments, and reconfiguring services to better meet patient needs. STUDY DESIGN: Acute stress 15-minute forced swimming (AFS) or CUMS protocols can induce the nonrandom MDD-FGID cluster. Multiple biological processes of rats with depression-like behaviours and gastrointestinal dysmobility will be captured under conditions of stress, and the Fructus Aurantii-Rhizoma Chuanxiong (ZQCX) decoction will be utilized to dock the MDD-FGID cluster. METHODS/RESULTS: Here, Rhizoma Chuanxiong, one of the seven components of Chaihu-shugan-San, elicited the best antidepressant effect on CUMS rats, followed by Fructus Aurantii. ZQCX reversed AFS-induced depression-like behaviours and gastrointestinal dysmobility by regulating the glutamatergic system, AMPAR/BDNF/mTOR/synapsin I pathway, ghrelin signalling and gastrointestinal nitric oxide synthase. Based on the bioethnopharmacological analysis strategy, the determined meranzin hydrate (MH) and senkyunolide I (SI) by UPLC-PDA, simultaneously absorbed by the jejunum and hippocampus of rats, have been considered major absorbed bioactive compounds acting on behalf of ZQCX. Cotreatment with MH and SI at an equivalent dose in ZQCX synergistically replicated over 50.33 % efficacy of the parent formula in terms of antidepressant and prokinetic actions by modulating neuroinflammation and ghrelin signalling. CONCLUSION: Brain-centric mind shifts require the integration of multiple central and peripheral systems and the elucidation of the underlying neurobiological mechanisms that ultimately contribute to novel therapeutic options. Ghrelin signalling and the immune system may partially underlie multimorbidity vulnerability, and ZQCX anchors stress-induced MDD-FGID clusters by docking them. Combining the results of micro details with the laws of the macro world may be more effective in finding treatments for MDD.
Assuntos
Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Estresse Psicológico , Animais , Medicamentos de Ervas Chinesas/farmacologia , Estresse Psicológico/tratamento farmacológico , Masculino , Ratos , Antidepressivos/farmacologia , Modelos Animais de Doenças , Gastroenteropatias/tratamento farmacológico , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Sistemas Neurossecretores/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Citrus/química , Fator Neurotrófico Derivado do Encéfalo/metabolismoRESUMO
From the earliest days of the coronavirus disease 2019 (COVID-19) pandemic, there have been reports of significant neurological and psychological symptoms following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This narrative review is designed to examine the potential psychoneuroendocrine pathogenic mechanisms by which SARS-CoV-2 elicits psychiatric sequelae as well as to posit potential pharmacologic strategies to address and reverse these pathologies. Following a brief overview of neurological and psychological sequelae from previous viral pandemics, we address mechanisms by which SARS-CoV-2 could enter or otherwise elicit changes in the CNS. We then examine the hypothesis that COVID-19-induced psychiatric disorders result from challenges to the neuroendocrine system, in particular the hypothalamic-pituitary-adrenal stress axis and monoamine synthesis, physiological mechanisms that are only further enhanced by the pandemic-induced social environment of fear, isolation, and socioeconomic pressure. Finally, we evaluate several FDA-approved therapeutics in the context of COVID-19-induced psychoneuroendocrine disorders.
Assuntos
COVID-19/virologia , Viroses do Sistema Nervoso Central/virologia , Sistema Nervoso Central/virologia , Sistemas Neurossecretores/virologia , SARS-CoV-2/patogenicidade , Anti-Inflamatórios/uso terapêutico , Antidepressivos/uso terapêutico , Antivirais/uso terapêutico , COVID-19/fisiopatologia , COVID-19/psicologia , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiopatologia , Viroses do Sistema Nervoso Central/tratamento farmacológico , Viroses do Sistema Nervoso Central/fisiopatologia , Viroses do Sistema Nervoso Central/psicologia , Interações Hospedeiro-Patógeno , Humanos , Neuroimunomodulação , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/metabolismo , Sistemas Neurossecretores/fisiopatologia , Prognóstico , Fatores de Risco , Internalização do Vírus , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Endocrine-disrupting chemicals have been shown to cause toxicity in different systems of the body including the endocrine, cardiovascular and nervous systems. This study aims to analyze the adverse effects of Methylparaben (MP) on cardiac functions, neurodevelopment, and behavior of zebrafish. METHODS AND RESULTS: Adult male and female zebrafish were exposed to MP for 30 days to study the toxicity effects. Zebrafish were grouped into control, solvent control, 1/10th (110 ppb), 1/100th, and 1/1000th (1 ppb) lethal concentration 50 of MP. Neurobehavioral assays, acetylcholinesterase (AChE) activity, serotonin levels, and expression of genes-Hypoxia-inducible factor 1 alpha, Neurotrophic Receptor Tyrosine Kinase, Paired box protein Pax-6, and tnnt2 were investigated in zebrafish. Results of the study showed more anxiety-like behavior in MP-treated female zebrafish when compared to males on chronic exposure. There was a dose-dependent reduction of AChE activity in both male and female zebrafish. Female zebrafish showed a dose-dependent increase in serotonin level on MP exposure while male zebrafish showed a dose-independent decrease in serotonin level. On MP exposure, there was also a dose-dependent dysregulation in the expression of cardiac hypoxia and neuronal differentiation-related genes in female zebrafish while a dose-independent change was observed in male zebrafish. CONCLUSION: Chronic MP exposure affects cardiac functions, neuronal functions, and behavior of zebrafish by exhibiting changes in AChE activity, serotonin levels, and altering the expression of genes related to cardiac hypoxia and neuronal differentiation even at sub-lethal doses.
Assuntos
Acetilcolinesterase/metabolismo , Ansiedade/metabolismo , Disruptores Endócrinos/toxicidade , Parabenos/toxicidade , Serotonina/metabolismo , Animais , Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Sistemas Neurossecretores/efeitos dos fármacos , Caracteres Sexuais , Testes de Toxicidade Subcrônica , Peixe-ZebraRESUMO
Social isolation and the disruption of established social bonds contribute to several physical and psychological health issues. Animal models are a useful tool for investigating consequences of social stress, including social isolation. The current study examined morphological changes in the basolateral amygdala (BLA) and affect-related behavioral and endocrine changes due to prolonged social isolation, using the translational prairie vole model (Microtus ochrogaster). Adult male prairie voles were either socially paired (control) or isolated from a same-sex sibling for 4 weeks. Following this 4-week period, a subset of animals (n = 6 per condition) underwent a series of behavioral tasks to assess affective, social, and stress-coping behaviors. Plasma was collected following the last behavioral task for stressor-induced endocrine assays. Brains were collected from a separate subset of animals (n = 10 per condition) following the 4-week social housing period for dendritic structure analyses in the BLA. Social isolation was associated with depressive- and anxiety-like behaviors, as well as elevated oxytocin reactivity following a social stressor. Social isolation was also associated with altered amount of dendritic material in the BLA, with an increase in spine density. These results provide further evidence that social isolation may lead to the development of affective disorders. Dysfunction in the oxytocin system and BLA remodeling may mediate these behavioral changes. Further research will promote an understanding of the connections between oxytocin function and structural changes in the BLA in the context of social stress. This research can facilitate novel treatments for alleviating or preventing behavioral and physiological consequences of social stressors in humans.
Assuntos
Arvicolinae/fisiologia , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Ocitocina/farmacologia , Isolamento Social/psicologia , Estresse Psicológico/fisiopatologia , Análise e Desempenho de Tarefas , Animais , Comportamento Animal/fisiologia , Corticosterona/sangue , Dendritos , Masculino , Sistemas Neurossecretores/efeitos dos fármacosRESUMO
Deoxynivalenol, a type B trichothecene mycotoxin produced by Fusarium species of fungi, is a ubiquitious contaminant of cereal grains worldwide. Chronic, low dose consumption of feeds contaminated with DON is associated with a wide range of symptoms in terrestrial and aquatic species including decreased feed intake and feed refusal, reduced weight gain, and altered nutritional efficiency. Acute, high dose exposure to DON may be associated with more severe symptoms such as vomiting, diarrhea, intestinal inflammation and gastrointestinal hemorrhage. The toxicity of DON is partly related to its ability to disrupt eukaryotic protein synthesis via binding to the peptidyl transferase site of the ribosome. Moreover, DON exerts its effects at the cellular level by activating mitogen activated protein kinases (MAPK) through a process known as the ribotoxic stress response (RSR). The outcome of DON-associated MAPK activation is dose and duration dependent; acute low dose exposure results in immunostimulation characterized by the upregulation of cytokines, chemokines and other proinflammatory-related proteins, whereas longer term exposure to higher doses generally results in apoptosis, cell cycle arrest, and immunosuppression. The order of decreasing sensitivity to DON is considered to be: swine > rats > mice > poultry ≈ ruminants. However, studies conducted within the past 10 years have demonstrated that some species of fish, such as rainbow trout, are highly sensitive to DON. The aims of this review are to explore the effects of DON on terrestrial and aquatic species as well as its mechanisms of action, metabolism, and interaction with other Fusarium mycotoxins. Notably, a considerable emphasis is placed on reviewing the effects of DON on different species of fish.
Assuntos
Micotoxinas/toxicidade , Tricotecenos/toxicidade , Animais , Organismos Aquáticos/efeitos dos fármacos , Peixes , Sistemas Neurossecretores/efeitos dos fármacosRESUMO
Here, we report the participation of N-methyl-D-aspartate (NMDA) glutamate receptor in the mediation of cardiovascular and circulating vasopressin responses evoked by a hemorrhagic stimulus. In addition, once NMDA receptor activation is a prominent mechanism involved in nitric oxide (NO) synthesis in the brain, we investigated whether control of hemorrhagic shock by NMDA glutamate receptor was followed by changes in NO synthesis in brain supramedullary structures involved in cardiovascular and neuroendocrine control. Thus, we observed that intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK801, 0.3 mg/kg) delayed and reduced the magnitude of hemorrhage-induced hypotension. Besides, hemorrhage induced a tachycardia response in the posthemorrhage period (i.e., recovery period) in control animals, and systemic treatment with MK801 caused a bradycardia response during hemorrhagic shock. Hemorrhagic stimulus increased plasma vasopressin levels during the recovery period and NMDA receptor antagonism increased concentration of this hormone during both the hemorrhage and postbleeding periods in relation to control animals. Moreover, hemorrhagic shock caused a decrease in NOx levels in the paraventricular nucleus of the hypothalamus (PVN), amygdala, bed nucleus of the stria terminalis (BNST), and ventral periaqueductal gray matter (vPAG). Nevertheless, treatment with MK801 did not affect these effects. Taken together, these results indicate that the NMDA glutamate receptor is involved in the hemorrhagic shock by inhibiting circulating vasopressin release. Our data also suggest a role of the NMDA receptor in tachycardia, but not in the decreased NO synthesis in the brain evoked by hemorrhage.
Assuntos
Bradicardia/induzido quimicamente , Sistema Cardiovascular/metabolismo , Maleato de Dizocilpina/administração & dosagem , Choque Hemorrágico/metabolismo , Vasopressinas/sangue , Animais , Bradicardia/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Sistema Cardiovascular/efeitos dos fármacos , Modelos Animais de Doenças , Maleato de Dizocilpina/efeitos adversos , Injeções Intraperitoneais , Masculino , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/metabolismo , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
Polycystic ovarian syndrome (PCOS), the most common endocrinopathy affecting women worldwide, is characterized by elevated luteinizing hormone (LH) pulse frequency due to the impaired suppression of gonadotrophin-releasing hormone (GnRH) release by steroid hormone negative feedback. Although neurons that co-express kisspeptin, neurokinin B, and dynorphin (KNDy cells) were recently defined as the GnRH/LH pulse generator, little is understood about their role in the pathogenesis of PCOS. We used a prenatal androgen-treated (PNA) mouse model of PCOS to determine whether changes in KNDy neurons or their afferent network underlie altered negative feedback. First, we identified elevated androgen receptor gene expression in KNDy cells of PNA mice, whereas progesterone receptor and dynorphin gene expression was significantly reduced, suggesting elevated androgens in PCOS disrupt progesterone negative feedback via direct actions upon KNDy cells. Second, we discovered GABAergic and glutamatergic synaptic input to KNDy neurons was reduced in PNA mice. Retrograde monosynaptic tract-tracing revealed a dramatic reduction in input originates from sexually dimorphic afferents in the preoptic area, anteroventral periventricular nucleus, anterior hypothalamic area and lateral hypothalamus. These results reveal 2 sites of neuronal alterations potentially responsible for defects in negative feedback in PCOS: changes in gene expression within KNDy neurons, and changes in synaptic inputs from steroid hormone-responsive hypothalamic regions. How each of these changes contribute to the neuroendocrine phenotype seen in in PCOS, and the role of specific sets of upstream KNDy afferents in the process, remains to be determined.
Assuntos
Androgênios/sangue , Neurônios/patologia , Síndrome do Ovário Policístico/patologia , Efeitos Tardios da Exposição Pré-Natal , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/metabolismo , Androgênios/farmacologia , Animais , Modelos Animais de Doenças , Dinorfinas/metabolismo , Feminino , Kisspeptinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurocinina B/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/fisiologia , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/metabolismo , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/metabolismo , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Síndrome do Ovário Policístico/psicologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/psicologiaRESUMO
The acylated peptide hormone ghrelin impacts a wide range of physiological processes but is most well known for controlling hunger and metabolic regulation. Ghrelin requires a unique posttranslational modification, serine octanoylation, to bind and activate signalling through its cognate GHS-R1a receptor. Ghrelin acylation is catalysed by ghrelin O-acyltransferase (GOAT), a member of the membrane-bound O-acyltransferase (MBOAT) enzyme family. The ghrelin/GOAT/GHS-R1a system is defined by multiple unique aspects within both protein biochemistry and endocrinology. Ghrelin serves as the only substrate for GOAT within the human proteome and, among the multiple hormones involved in energy homeostasis and metabolism such as insulin and leptin, acts as the only known hormone in circulation that directly stimulates appetite and hunger signalling. Advances in GOAT enzymology, structural modelling and inhibitor development have revolutionized our understanding of this enzyme and offered new tools for investigating ghrelin signalling at the molecular and organismal levels. In this review, we briefly summarize the current state of knowledge regarding ghrelin signalling and ghrelin/GOAT enzymology, discuss the GOAT structural model in the context of recently reported MBOAT enzyme superfamily member structures, and highlight the growing complement of GOAT inhibitors that offer options for both ghrelin signalling studies and therapeutic applications.
Assuntos
Aciltransferases/metabolismo , Grelina/metabolismo , Sistemas Neurossecretores/metabolismo , Processamento de Proteína Pós-Traducional , Transdução de Sinais , Acilação , Aciltransferases/antagonistas & inibidores , Aciltransferases/química , Animais , Sítios de Ligação , Proteínas de Transporte , Desenvolvimento de Medicamentos , Grelina/química , Humanos , Modelos Moleculares , Sistemas Neurossecretores/efeitos dos fármacos , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Especificidade por SubstratoRESUMO
BACKGROUND: Hypertension is a kind of cardiovascular syndrome with the main clinical manifestation of continuous increase of systemic arterial blood pressure. Hypertension coexists with other cardiovascular risk factors and is an important risk factor for cardiovascular and cerebrovascular diseases. Acupuncture is an important part of Traditional Chinese Medicine intervention. The antihypertensive effect of acupuncture on hypertension is based on the neuroendocrine system, characterized by multichannel and multitarget. This study aims to provide latest and updated proof of systematic review to assess the effectiveness and safety of acupuncture for hypertension. METHODS: We will systematically search 9 databases from their inceptions to February 2021. Only randomized controlled trials of acupuncture combined with western medicine in the treatment of hypertension will meet the inclusion criteria. The main outcome measures we focus on include clinical efficacy, syndrome efficacy, Traditional Chinese Medicine syndrome score, diastolic and systolic blood pressure changes, blood pressure variability, heart rate variability, pulse rate variability, and adverse reactions. The research screening, data extraction, and risk of bias assessment will be employed by 2 reviewers independently, and disagreement will be decided by a third senior reviewer. The Revman 5.3 software will be used for meta-analysis. The confidence of proof will be rated adopting grading of recommendations assessment, development and evaluation tool and methodological quality of this research will be assessed using assessment of multiple systematic reviews-2 and risk of bias in systematic reviews. The publication quality will be evaluated by preferred reporting items for systematic reviews and meta-analyses (PRISMA). RESULTS: This systematic review (SR) will provide evidence-based medical evidence for hypertension therapy by acupuncture combined with western medicine and we will submit the findings of this SR for peer-review publication. CONCLUSIONS: This SR will provide latest and updated summary proof for assessing the effectiveness and safety of acupuncture for hypertension. REGISTRATION NUMBER: INPLASY 202150047.
Assuntos
Terapia por Acupuntura/métodos , Anti-Hipertensivos/administração & dosagem , Diuréticos/administração & dosagem , Medicina Baseada em Evidências/métodos , Hipertensão/tratamento farmacológico , Terapia por Acupuntura/efeitos adversos , Adulto , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Terapia Combinada/métodos , Diuréticos/efeitos adversos , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Metanálise como Assunto , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Resultado do TratamentoAssuntos
Analgésicos Opioides/efeitos adversos , Dor Crônica/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Analgésicos Opioides/administração & dosagem , Animais , Dor Crônica/diagnóstico , Dor Crônica/imunologia , Esquema de Medicação , Humanos , Hospedeiro Imunocomprometido , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/fisiopatologia , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Staphylococcus aureus induced brain abscess is a critical health concern throughout the developing world. The conventional surgical intervention could not regulate the abscess-induced brain inflammation. Thus further study over the alternative therapeutic strategy for treating a brain abscess is of high priority. The resident glial cells recognize the invading S. aureus by their cell surface Toll-like receptor-2 (TLR-2). Glucocorticoid receptor (GR) was known for its immunosuppressive effects. In this study, an attempt had been taken to utilize the functional relationship or cross-talking between TLR-2 and GR during the pathogenesis of brain abscesses. Here, the combination of an antibiotic (i.e. ciprofloxacin) and dexamethasone was used to regulate the brain inflammation either in TLR-2 or GR blocking condition. We were also interested to figure out the possible impact of alternative therapy on behavioral impairments. The results indicated that combination treatment during TLR-2 blockade significantly reduced the bacterial burden and abscess area score in the infected brain. However, marked improvements were observed in anxiety, depression-like behavior, and motor co-ordination. The combination treatment after TLR-2 blocking effectively scavenged free radicals (H2O2, superoxide anion, and NO) through modulating antioxidant enzyme activities that ultimately control S. aureus induced glial reactivity possibly via up-regulating GR expression. The exogenous dexamethasone might regulate the GR expression in the brain by increasing the corticosterone concentration and the GC-GR mediated signaling. Therefore, this in-vivo study demonstrates the possible regulatory mechanism of bacterial brain abscess that involved TLR-2 and GR as a part of neuroendocrine-immune interaction.
Assuntos
Abscesso Encefálico/tratamento farmacológico , Ciprofloxacina/farmacologia , Dexametasona/farmacologia , Doenças Neuroinflamatórias/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Abscesso Encefálico/complicações , Abscesso Encefálico/imunologia , Abscesso Encefálico/microbiologia , Ciprofloxacina/uso terapêutico , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Quimioterapia Combinada , Humanos , Masculino , Camundongos , Doenças Neuroinflamatórias/diagnóstico , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/microbiologia , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/imunologia , Receptores de Glucocorticoides/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/imunologia , Receptor 2 Toll-Like/metabolismoRESUMO
Human immunodeficiency virus (HIV) is associated with neuroendocrine dysfunction which may contribute to co-morbid stress-sensitive disorders. The hypothalamic-pituitary-adrenal (HPA) or -gonadal (HPG) axes are perturbed in up to 50% of HIV patients. The mechanisms are not known, but we have found the HIV-1 trans-activator of transcription (Tat) protein to recapitulate the clinical phenotype in male mice. We hypothesized that HPA and/or HPG dysregulation contributes to Tat-mediated interactions with oxycodone, an opioid often prescribed to HIV patients, in females. Female mice that conditionally-expressed the Tat1-86 protein [Tat(+) mice] or their counterparts that did not [Tat(-) control mice] were exposed to forced swim stress (or not) and behaviorally-assessed for motor and anxiety-like behavior. Some mice had glucocorticoid receptors (GR) or corticotropin-releasing factor receptors (CRF-R) pharmacologically inhibited. Some mice were ovariectomized (OVX). As seen previously in males, Tat elevated basal corticosterone levels and potentiated oxycodone's psychomotor activity in females. Unlike males, females did not demonstrate adrenal insufficiency and oxycodone potentiation was not regulated by GRs or CRF-Rs. Rather OVX attenuated Tat/oxycodone interactions. Either Tat or oxycodone increased anxiety-like behavior and their combination increased hypothalamic allopregnanolone. OVX increased basal hypothalamic allopregnanolone and obviated Tat or oxycodone-mediated fluctuations. Together, these data provide further evidence for Tat-mediated dysregulation of the HPA axis and reveal the importance of HPG axis regulation in females. HPA/HPG disruption may contribute vulnerability to affective and substance use disorders.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1/fisiologia , Sistemas Neurossecretores/metabolismo , Sistemas Neurossecretores/fisiopatologia , Oxicodona/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Animais , Comportamento Animal , Modelos Animais de Doenças , Ciclo Estral , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Camundongos , Atividade Motora , Sistemas Neurossecretores/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Pregnanolona/sangue , Pregnanolona/metabolismo , Esteroides/sangueRESUMO
Acquired treatment resistance is an important cause of death in prostate cancer, and this study aimed to explore the mechanisms of chemotherapy resistance in prostate cancer. We employed castration-resistant prostate cancer (CRPC), neuroendocrine prostate cancer (NEPC), and chemotherapy-resistant prostate cancer datasets to screen for potential target genes. The Cancer Genome Atlas (TCGA) was used to detect the correlation between the target genes and prognosis and clinical characteristics. Nei endonuclease VIII-like 3 (NEIL3) knockdown cell lines were constructed with RNA interference. Prostate cancer cells were treated with enzalutamide for the androgen deprivation therapy (ADT) model, and with docetaxel and cisplatin for the chemotherapy model. Apoptosis and the cell cycle were examined using flow cytometry. RNA sequencing and western blotting were performed in the knockdown Duke University 145 (DU145) cell line to explore the possible mechanisms. The TCGA dataset demonstrated that high NEIL3 was associated with a high T stage and Gleason score, and indicated a possibility of lymph node metastasis, but a good prognosis. The cell therapy models showed that the loss of NEIL3 could promote the chemotherapy resistance (but not ADT resistance) of prostate cancer (PCa). Flow cytometry revealed that the loss of NEIL3 in PCa could inhibit cell apoptosis and cell cycle arrest under cisplatin treatment. RNA sequencing showed that the knockdown of NEIL3 changes the expression of neuroendocrine-related genes. Further western blotting revealed that the loss of NEIL3 could significantly promote the phosphorylation of ATR serine/threonine kinase (ATR) and ATM serine/threonine kinase (ATM) under chemotherapy, thus initiating downstream pathways related to DNA repair. In summary, the loss of NEIL3 promotes chemotherapy resistance in prostate cancer, and NEIL3 may serve as a diagnostic marker for chemotherapy-resistant patients.
Assuntos
Resistencia a Medicamentos Antineoplásicos , N-Glicosil Hidrolases/deficiência , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , N-Glicosil Hidrolases/genética , N-Glicosil Hidrolases/metabolismo , Invasividade Neoplásica , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Fase S/efeitos dos fármacosRESUMO
Phthalates, as other endocrine disrupting chemicals (EDCs), may alter the homeostasis and the action of hormones and signaling molecules, causing adverse health outcomes. This is true especially for infants, who are both more exposed and sensitive to their effects. Phthalates are particularly harmful when the exposure occurs during certain critical temporal windows of the development, such as the prenatal and the early postnatal phases. Phthalates may also interfere with the neuroendocrine systems (e.g., thyroid hormone signaling or metabolism), causing disruption of neuronal differentiation and maturation, increasing the risk of behavioral and cognitive disorders (ADHD and autistic behaviors, reduced mental, psychomotor, and IQ development, and emotional problems). Despite more studies being needed to better understand the role of these substances, plenty of evidence suggests the impact of phthalates on the neuroendocrine system development and function. This review aims to update the knowledge on the neuroendocrine consequences of neonatal and perinatal exposure to phthalates.
Assuntos
Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Transtornos do Neurodesenvolvimento/fisiopatologia , Sistemas Neurossecretores/efeitos dos fármacos , Ácidos Ftálicos/toxicidade , Exposição Ambiental , Feminino , Humanos , Transtornos do Neurodesenvolvimento/induzido quimicamente , Sistemas Neurossecretores/patologia , GravidezRESUMO
Prolactin is a proteic hormone best known for its role in enabling the production of milk by female mammals. Secreted by the pituitary gland in response to the stimuli of eating, estrogen treatment, mating, ovulation and nursing, prolactin is involved in over 300 separate processes in a range of vertebrates, including humans. The hormone is released in a pulsatile manner and plays an essential role in metabolism, as well as in the regulation of the immune system and pancreatic development. Nevertheless, prolactin exerts other relevant roles, as it acts at the central nervous system level to modulate behavior, arousal and sexuality. In this experts' opinion, we aim to give insights into the main activities of prolactin to advance the ability of medical doctors and specialists in obstetrics and gynecology to provide more emphasis in their clinical practices to the link between prolactin and sexuality.
Assuntos
Envelhecimento/fisiologia , Prolactina/fisiologia , Reprodução/fisiologia , Comportamento Sexual/fisiologia , Prova Pericial , Feminino , Humanos , Hiperprolactinemia/metabolismo , Hiperprolactinemia/fisiopatologia , Sistemas Neurossecretores/efeitos dos fármacos , Gravidez , Prolactina/farmacologia , Comportamento Sexual/efeitos dos fármacosRESUMO
BACKGROUND: Accumulating evidence has established a role for the orexigenic hormone ghrelin in alcohol-seeking behaviors. Accordingly, the ghrelin system may represent a potential pharmacotherapeutic target for alcohol use disorder. Ghrelin modulates several neuroendocrine pathways, such as appetitive, metabolic, and stress-related hormones, which are particularly relevant in the context of alcohol use. The goal of the present study was to provide a comprehensive assessment of neuroendocrine response to exogenous ghrelin administration, combined with alcohol, in heavy-drinking individuals. METHODS: This was a randomized, crossover, double-blind, placebo-controlled human laboratory study, which included 2 experimental alcohol administration paradigms: i.v. alcohol self-administration and i.v. alcohol clamp. Each paradigm consisted of 2 counterbalanced sessions of i.v. ghrelin or placebo administration. Repeated blood samples were collected during each session, and peripheral concentrations of the following hormones were measured: leptin, glucagon-like peptide-1, pancreatic polypeptide, gastric inhibitory peptide, insulin, insulin-like growth factor-1, cortisol, prolactin, and aldosterone. RESULTS: Despite some statistical differences, findings were consistent across the 2 alcohol administration paradigms: i.v. ghrelin, compared to placebo, increased blood concentrations of glucagon-like peptide-1, pancreatic polypeptide, cortisol, and prolactin, both acutely and during the whole session. Lower levels of leptin and higher levels of aldosterone were also found during the ghrelin vs placebo session. CONCLUSION: These findings, gathered from a clinically relevant sample of heavy-drinking individuals with alcohol use disorder, provide a deeper insight into the complex interplay between ghrelin and appetitive, metabolic, and stress-related neuroendocrine pathways in the context of alcohol use.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Alcoolismo/sangue , Depressores do Sistema Nervoso Central/farmacologia , Fissura/efeitos dos fármacos , Etanol/farmacologia , Grelina/farmacologia , Sistemas Neurossecretores/efeitos dos fármacos , Adulto , Depressores do Sistema Nervoso Central/administração & dosagem , Método Duplo-Cego , Etanol/administração & dosagem , Feminino , Grelina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , AutoadministraçãoRESUMO
In teleost fish, radial glial cells (RGCs) are progenitor cells for neurons and the major cell type synthesizing neuroestrogens. We hypothesized that chemical exposure impairs mitochondrial bioenergetics of RGCs, which then may lead to downstream consequences for neuroestrogen production. Here we provide proof of concept that mitochondria of RGCs can be perturbed by fungicides. We isolated RGCs from a mixed sex population of goldfish (Carassius auratus) and measured metabolic capacity of primary cells to a model mitotoxin fluazinam, a broad-spectrum fungicide that inhibits mitochondria electron transport chain (or ETC) Complex I. Using immunocytochemistry and real-time PCR, we demonstrate that the goldfish primary cell cultures are highly enriched for glia after multiple passages. Cytotoxicity assays revealed that glia treated with >25 µM fluazinam for 24 and 48-h showed reduced viability. As such, metabolic assays were conducted with non-cytotoxic concentrations (0.25-12.5 µM). Fluazinam did not affect oxygen consumption rates of RGCs at 24 h, but after 48 h, oligomycin induced ATP-linked respiration was decreased by both 6.25 and 12.5 µM fluazinam. Moreover, concentrations as low as 0.25 µM disrupted the mitochondrial membrane potential of RGCs, reflecting strong uncoupling effects of the fungicide on mitochondria. Here we provide proof of concept that mitochondrial bioenergetics of teleostean RGCs can be responsive to agrochemicals. Additional studies are required to address low-dose exposures in vivo and to determine if metabolic disruption impairs neuroendocrine functions of RGCs. We propose this mechanism constitutes a novel aspect of neuroendocrine disruption, significant because dysregulation of neuron-glia communication is expected to contribute to neuroendocrine disruption.