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1.
Cell Adh Migr ; 15(1): 261-271, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34494935

RESUMO

Serotonin is well known as a neurotransmitter. Its roles in neuronal processes such as learning, memory or cognition are well established, and also in disorders such as depression, schizophrenia, bipolar disorder, and dementia. However, its effects on adhesion and cytoskeletal remodelling which are strongly affected by 5-HT receptors, are not as well studied with some exceptions for e.g. platelet aggregation. Neuronal function is strongly dependent on cell-cell contacts and adhesion-related processes. Therefore the role played by serotonin in psychiatric illness, as well as in the positive and negative effects of neuropsychiatric drugs through cell-related adhesion can be of great significance. In this review, we explore the role of serotonin in some of these aspects based on recent findings.


Assuntos
Adesão Celular/fisiologia , Movimento Celular/fisiologia , Citoesqueleto/fisiologia , Neurotransmissores/fisiologia , Serotonina/fisiologia , Animais , Humanos , Transtornos Mentais/metabolismo
2.
Environ Sci Technol ; 55(17): 11894-11905, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34488355

RESUMO

Elevated concentrations of dietary selenium (Se) cause abnormalities and extirpation of fish inhabiting in Se-contaminated environments. However, its effect on fish behavior and the underlying mechanisms remain largely unknown. In this study, two-month-old zebrafish (Danio rerio) was fed seleno-l-methionine (Se-Met) at environmentally relevant concentrations (i.e., control (2.61), low (5.43), medium (12.16), and high (34.61) µg Se/g dry weight (dw), respectively, corresponding to the C, L, M, and H treatments) for 60 days. Targeted metabolomics, histopathological, and targeted transcriptional endpoints were compared to behavioral metrics to evaluate the effects of dietary exposure to Se-Met . The results showed that the levels of total Se and malondialdehyde in fish brains were increased in a dose-dependent pattern. Meanwhile, mitochondrial damages and decreased activities of the mitochondria respiratory chain complexes were observed in the neurons at the M and H treatments. In addition, dietary Se-Met affected neurotransmitters, metabolites, and transcripts of the genes associated with the dopamine, serotonin, gamma-aminobutyric acid, acetylcholine, and histamine signaling pathways in zebrafish brains at the H treatments. The total swimming distance and duration in the Novel Arm were lowered in fish from the H treatment. This study has demonstrated that dietary Se-Met affects the ultrastructure of the zebrafish brain, neurotransmitters, and associated fish behaviors and may help enhance adverse outcome pathways for neurotransmitter-behavior key events in zebrafish.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Antioxidantes , Encéfalo , Neurotransmissores , Selenometionina
3.
Adv Exp Med Biol ; 1331: 249-254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34453303

RESUMO

In these last decades, emotions and feelings, neglected for centuries by experimental sciences, have become the topic of extensive neuroscientific research. Currently, love, the most typically human feeling, can be viewed as the result of different phases (steps), each regulated by evolutionary well-conserved and integrated neural substrates. We have proposed that the early stage, generally called romantic love, is the result of the activation of the brain limbic structures regulating fear/anxiety reactions leading to changes of major neurotransmitters, such as increased monoamine levels and decreased serotonin concentrations. The second stage of love is mainly underlain by the structures regulating the attachment system and involving oxytocin and vasopressin neuropeptides and neurotrophins. This would explain why the positive effects of love can be extremely beneficial for both mental and physical health.However, available data are still limited, and the proposed models, although supported by converging data, should be considered speculative and oversimplified. The hope is that neuroscience will permit to shed light on love, one of the most intriguing, and still largely unknown mysteries of human nature.


Assuntos
Encéfalo , Amor , Emoções , Humanos , Neurotransmissores , Ocitocina
4.
Int J Mol Sci ; 22(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34445312

RESUMO

"Neuroplasticity" is often evoked to explain adaptation and compensation after acute lesions of the Central Nervous System (CNS). In this study, we investigated the modification of 80 genes involved in synaptic plasticity at different times (24 h, 8 and 45 days) from the traumatic spinal cord injury (SCI), adopting a bioinformatic analysis. mRNA expression levels were analyzed in the motor cortex, basal ganglia, cerebellum and in the spinal segments rostral and caudal to the lesion. The main results are: (i) a different gene expression regulation is observed in the Spinal Cord (SC) segments rostral and caudal to the lesion; (ii) long lasting changes in the SC includes the extracellular matrix (ECM) enzymes Timp1, transcription regulators (Egr, Nr4a1), second messenger associated proteins (Gna1, Ywhaq); (iii) long-lasting changes in the Motor Cortex includes transcription regulators (Cebpd), neurotransmitters/neuromodulators and receptors (Cnr1, Gria1, Nos1), growth factors and related receptors (Igf1, Ntf3, Ntrk2), second messenger associated proteins (Mapk1); long lasting changes in Basal Ganglia and Cerebellum include ECM protein (Reln), growth factors (Ngf, Bdnf), transcription regulators (Egr, Cebpd), neurotransmitter receptors (Grin2c). These data suggest the molecular mapping as a useful tool to investigate the brain and SC reorganization after SCI.


Assuntos
Encéfalo/metabolismo , Plasticidade Neuronal/genética , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Transcriptoma , Animais , Feminino , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , Neurotransmissores/genética , Neurotransmissores/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/genética , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
5.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360837

RESUMO

Skin pigmentation can occur due to increased melanin, including melanocyte proliferation, melanin biosynthesis, or melanocyte migration. There are many factors that influence the melanin production process, but the role of neurotransmitters in this process is still unclear. We found that histamine and serotonin influence the different stages of melanogenesis and melanogenesis, which increase melanogenesis. Since then, several related papers have been published, and from these papers, it has been recognised that the role of neurotransmitters in skin-pigment-related diseases needs to be summarised. By introducing the role of neurotransmitters in the regulation of various pigment disorders, including vitiligo and melasma, through this review, many researchers can be expected to try to apply neurotransmitter-related agonists and antagonists as treatments for skin pigment disorders.


Assuntos
Neurotransmissores/metabolismo , Transtornos da Pigmentação/metabolismo , Receptores de Neurotransmissores/metabolismo , Pigmentação da Pele , Animais , Humanos , Melaninas/metabolismo , Melanócitos/metabolismo , Melanócitos/fisiologia , Melanose , Neurotransmissores/fisiologia , Transtornos da Pigmentação/fisiopatologia , Receptores de Neurotransmissores/fisiologia , Vitiligo
6.
Biomed Khim ; 67(4): 323-330, 2021 Jul.
Artigo em Russo | MEDLINE | ID: mdl-34414890

RESUMO

We investigated the levels of biogenic monoamines and their metabolites in the rat hypothalamus, midbrain and cerebellum in acute complex intoxication with morphine and alcohol. The distinctive features of neurotransmitter disorders in various parts of the rat brain under a single exposure to ethanol and morphine, as well as the differences between acute morphine-alcohol and alcohol-morphine intoxication were established. Complex intoxication with alcohol and morphine resulted in signs of dopamine consumption only in the hypothalamus, regardless of the order of alcohol and morphine administration. Under conditions of alcohol-morphine intoxication an increase in the level of metabolites of the serotonergic system was noted in the investigated parts of the brain. In the midbrain and cerebellum the manifestation of combined action of ethanol and morphine is mainly determined by the effect of the last of the administered substances. There are features of changes in the indices of the dopaminergic and serotonergic systems in these experimental conditions, confirmed by the processes of dopamine catabolism and a decrease in the norepinephrine and serotonin concentration in the hypothalamus, which are not observed under individual action of ethanol and morphine.


Assuntos
Morfina , Neurotransmissores , Animais , Encéfalo , Etanol/toxicidade , Ratos , Serotonina
7.
Phytomedicine ; 90: 153669, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34334273

RESUMO

BACKGROUND: Depression, as a prevalent and debilitating psychiatric disease, severely decreases the life quality of individuals and brings heavy burdens to the whole society. Currently, some antidepressants are applied in the treatment of severe depressive symptoms, while there are still some undesirable drawbacks. Paeoniflorin is a monoterpenoid glycoside that was firstly extracted from Paeonia lactiflora Pall, a traditional Chinese herb that is widely used in the Chinese herbal formulas for treating depression. PURPOSE: This review summarized the previous pre-clinical studies of paeoniflorin in treating depression and further discussed the potential anti-depressive mechanisms for that paeoniflorin to be further explored and utilized in the treatment of depression clinically. METHODS: Some electronic databases, e.g., PubMed and China National Knowledge Infrastructure, were searched from inception until April 2021. RESULTS: This review summarized the effective anti-depressive properties of paeoniflorin, which is related to its functions in the upregulation of the levels of monoaminergic neurotransmitters, inhibition of the hypothalamic-pituitary-adrenal axis hyperfunction, promotion of neuroprotection, promotion of hippocampus neurogenesis, and upregulation of brain-derived neurotrophic factor level, inhibition of inflammatory reaction, downregulation of nitric oxide level, etc. CONCLUSION: This review focused on the pre-clinical studies of paeoniflorin in depression and summarized the recent development of the anti-depressive mechanisms of paeoniflorin, which approves the role of paeoniflorin plays in anti-depression. However, more high-quality pre-clinical and clinical studies are expected to be conducted in the future.


Assuntos
Antidepressivos/farmacologia , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Neuroproteção , Humanos , Sistema Hipotálamo-Hipofisário , Neurotransmissores , Paeonia/química , Sistema Hipófise-Suprarrenal
8.
Life Sci ; 284: 119904, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34453945

RESUMO

AIM: Alcohol abuse is a significant causative factor of death worldwide. The Notch1 signaling pathway is involved in alcohol tolerance, withdrawal and dependence. Agomelatine is a known antidepressant acting as a melatonin receptor (MT1/2) agonist and a 5-hydroxytryptamine receptor-2C antagonist. However, its effects on alcohol cravings and alcohol withdrawal symptoms have not been investigated. In this study, we assessed the possibility of using agomelatine for the treatment of these symptoms in a rat model of alcoholism and the possible role of Notch1 signaling. MAIN METHODS: We induced alcoholism in rats using a free-choice drinking model for 60 days. From day 61, free-choice was continued until day 82 for the craving model, whereas only water was offered in the withdrawal model. Meanwhile, the treated groups for both models received agomelatine (50 mg/kg/day) orally from day 61 to 82, followed by behavioral, histopathological and biochemical assessment. KEY FINDINGS: Agomelatine treatment caused significant decrease in alcohol consumption with a positive effect on anxiety-like behavior in the open field, memory in the Morris water maze and immobility in the forced swim test. Moreover, agomelatine induced the expression of Notch1 pathway markers, including Notch1, NICD, CREB, CCNE-2, Hes-1, both total and phosphorylated ERK1/2, MMP9, Per2and RGS-2 in the hippocampal formation. By contrast, NMDAR expression was reduced. Furthermore, agomelatine normalized the serum levels of BDNF, cortisol, dopamine and glutamate which were disrupted by alcohol consumption. SIGNIFICANCE: Based on these findings, agomelatine reversed alcohol cravings and withdrawal symptoms associated with alcohol dependence by modulating the Notch1 signaling pathway.


Assuntos
Acetamidas/uso terapêutico , Bebidas Alcoólicas/efeitos adversos , Fissura , Receptor Notch1/metabolismo , Transdução de Sinais , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/metabolismo , Acetamidas/farmacologia , Animais , Ansiedade/patologia , Comportamento Animal/efeitos dos fármacos , Biomarcadores/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Hipocampo/metabolismo , Hidrocortisona/sangue , Masculino , Teste do Labirinto Aquático de Morris , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Neurotransmissores/sangue , Teste de Campo Aberto , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
9.
Talanta ; 234: 122620, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364429

RESUMO

We developed a methodology for rapid quantification of extracellular neurotransmitters in mouse brain by PESI/MS/MS and longitudinal data analysis using the R and Stan-based Bayesian state-space model. We performed a rapid analysis for quantifying extracellular l-glutamic acid (L-Glu) and gamma-aminobutyric acid (GABA) in the mouse striatum by combined use of probe electrospray ionization/tandem mass spectrometry (PESI/MS/MS) and in vivo brain microdialysis. We optimized the PESI/MS/MS parameters with the authentic L-Glu, GABA, L-Glu-13C5,15N1, and GABA-D6 standards. We constructed calibration curves of L-Glu and GABA with the stable isotope internal standard correction method (L-Glu-13C5,15N1, and GABA-D6), demonstrating sufficient linearity (R > 0.999). Additionally, the quantitative method for L-Glu and GABA was validated with low-, middle-, and high-quality control samples. The intra- and inter-day accuracy and precision were 0.4%-7.5% and 1.7%-5.4% for L-Glu, respectively, and 0.1%-4.8% and 2.1%-5.7% for GABA, respectively, demonstrating high reproducibility of the method. To evaluate the feasibility of this method, microdialyses were performed on free-moving mice that were stimulated by high-K+-induced depolarization under different sampling conditions: 1) every 5 min for 150 min (n = 2) and 2) every 1 min for 30 min (n = 3). We applied the R and Stan-based Bayesian state-space model to each mouse's time-series data considering autocorrelation, and the model successfully detected abnormal changes in the L-Glu and GABA levels in each mouse. Thus, the L-Glu and GABA levels in all microdialysates approximately increased up to two- and seven-fold levels through high-K+-induced depolarization. Additionally, a 1-min temporal resolution was achieved using this method, thereby successfully monitoring microenvironmental changes in the extracellular L-Glu and GABA of the mouse striatum. In conclusion, this methodology using PESI/MS/MS and Bayesian state-space model allowed easy monitoring of neurotransmitters at high temporal resolutions and appropriate data interpretation considering autocorrelation of time-series data, which will reveal hidden pathological mechanisms of brain diseases, such as Parkinson's disease and Huntington's disease in the future.


Assuntos
Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Animais , Teorema de Bayes , Encéfalo , Análise de Dados , Ácido Glutâmico , Camundongos , Microdiálise , Neurotransmissores , Reprodutibilidade dos Testes , Simulação de Ambiente Espacial
10.
Neuropharmacology ; 198: 108766, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34454912

RESUMO

The coronavirus disease 2019 (Covid-19) pandemic intensified the already catastrophic drug overdose and substance use disorder (SUD) epidemic, signaling a syndemic as social isolation, economic and mental health distress, and disrupted treatment services disproportionally impacted this vulnerable population. Along with these social and societal factors, biological factors triggered by intense stress intertwined with incumbent overactivity of the immune system and the resulting inflammatory outcomes may impact the functional status of the central nervous system (CNS). We review the literature concerning SARS-CoV2 infiltration and infection in the CNS and the prospects of synergy between stress, inflammation, and kynurenine pathway function during illness and recovery from Covid-19. Taken together, inflammation and neuroimmune signaling, a consequence of Covid-19 infection, may dysregulate critical pathways and underlie maladaptive changes in the CNS, to exacerbate the development of neuropsychiatric symptoms and in the vulnerability to develop SUD. This article is part of the special Issue on 'Vulnerabilities to Substance Abuse'.


Assuntos
COVID-19/epidemiologia , Uso Indevido de Medicamentos/estatística & dados numéricos , SARS-CoV-2 , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adaptação Psicológica , Enzima de Conversão de Angiotensina 2/fisiologia , Animais , Axônios/virologia , COVID-19/imunologia , COVID-19/fisiopatologia , COVID-19/psicologia , Comorbidade , Suscetibilidade a Doenças , Células Endoteliais/virologia , Humanos , Imunidade Inata , Inflamação/etiologia , Cinurenina/metabolismo , Neurônios/virologia , Neurotransmissores/metabolismo , Mucosa Olfatória/virologia , Pandemias , SARS-CoV-2/fisiologia , Isolamento Social , Estresse Psicológico , Transtornos Relacionados ao Uso de Substâncias/etiologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Triptofano/metabolismo , Tropismo Viral
11.
Biomed Res Int ; 2021: 6681397, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368355

RESUMO

Early life stress is an important determinant for developing depression later in life. It is reported that maternal separation (MS) could trigger stress sensitivity in adulthood when exposed to stress again. However, it could also result in resilience to stress-induced depression. The conclusions are contradictory. To address this issue, C57BL/6N newborn pups were exposed to either daily short MS (MS for 15 min per day; MS15) or prolonged MS (MS for 180 min per day; MS180) from the first day postpartum (PD1) to PD21. Adult mice were then subjected to chronic unpredictable mild stress (CUMS) exposure from PD64 to PD105. The behavior tests such as the forced swimming test (FST), tail suspension test (TST), and open-field test were performed once a week during this time. Besides, the hippocampal neurosteroids, serum stress hormones, and hippocampal monoamine neurotransmitters were measured at PD106. We found that mice in the MS180 group displayed the reduced struggling time and the increased latency to immobility in both FST and TST. However, there was no significant difference in the MS15 group. The levels of hippocampal neurosteroids (progesterone and allopregnanolone) were decreased, and the serum levels of corticosterone, corticotropin-releasing hormone, and adrenocorticotropic hormone were overexpressed in the MS180 group. Besides, the expressions of monoamine neurotransmitters such as 5-hydroxytryptamine and 5-hydroxy indole acetic acid significantly decreased in the MS180 group, but not in the MS15 group. All findings revealed that prolonged MS, rather than short MS, could increase the susceptibility to depression-like behavior when reexposed to stress in adulthood. However, future studies are warranted to identify the underlying neuromolecular mechanism of the MS experience on the susceptibility to adult stress reexposure.


Assuntos
Comportamento Animal , Depressão/complicações , Depressão/psicologia , Suscetibilidade a Doenças , Privação Materna , Estresse Psicológico/complicações , Animais , Doença Crônica , Feminino , Hormônios/sangue , Camundongos Endogâmicos C57BL , Neuroesteroides/farmacologia , Neurotransmissores/metabolismo , Natação
12.
Zoology (Jena) ; 148: 125958, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34399394

RESUMO

Heteropneustes fossilis is an air-breathing teleost inhabiting environments with very poor O2 conditions, and so it has evolved to cope with hypoxia. In the gills and respiratory air-sac, the sites for O2 sensing and the response to hypoxia rely on the expression of acetylcholine (Ach) acting via its nicotinic receptor (nAChR). This study examined the expression patterns of neuronal markers and some compounds in the NECs of the gills and respiratory air sac having an immunomodulatory function in mammalian lungs. Mucous cells, epithelial cells and neuroepithelial cells (NECs) were immunopositive to a variety of both neuronal markers (VAChT, nAChR, GABA-B-R1 receptor, GAD679) and the antimicrobial peptide piscidin, an evolutionary conserved humoral component of the mucosal immune system in fish. We speculate that Ach release via nAChR from mucous cells may be modulated by GABA production in the NECs and it is required for the induction of mucus production in both normoxic and hypoxic conditions. The presence of piscidin in mucous cells may act in synergy with the autocrine/paracrine signals of Ach and GABA binding to GABA B R1B receptor that may play a local immunomodulatory function in the mucous epithelia of the gills and the respiratory air sac. The potential role of the NECs in the immunobiological behaviour of the gill/air-sac is at moment a matter of speculation. The extent to which the NECs as such may participate is elusive at this stage and waits investigation.


Assuntos
Peixes-Gato/fisiologia , Brânquias/citologia , Muco/metabolismo , Células Neuroepiteliais/metabolismo , Neurotransmissores/metabolismo , Receptores de Neurotransmissores/metabolismo , Sacos Aéreos/citologia , Animais , Peixes-Gato/imunologia , Imunidade Celular , Receptores de Neurotransmissores/genética
13.
Biosensors (Basel) ; 11(6)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34204902

RESUMO

Neurotransmitters are biochemical molecules that transmit a signal from a neuron across the synapse to a target cell, thus being essential to the function of the central and peripheral nervous system. Dopamine is one of the most important catecholamine neurotransmitters since it is involved in many functions of the human central nervous system, including motor control, reward, or reinforcement. It is of utmost importance to quantify the amount of dopamine since abnormal levels can cause a variety of medical and behavioral problems. For instance, Parkinson's disease is partially caused by the death of dopamine-secreting neurons. To date, various methods have been developed to measure dopamine levels, and electrochemical biosensing seems to be the most viable due to its robustness, selectivity, sensitivity, and the possibility to achieve real-time measurements. Even if the electrochemical detection is not facile due to the presence of electroactive interfering species with similar redox potentials in real biological samples, numerous strategies have been employed to resolve this issue. The objective of this paper is to review the materials (metals and metal oxides, carbon materials, polymers) that are frequently used for the electrochemical biosensing of dopamine and point out their respective advantages and drawbacks. Different types of dopamine biosensors, including (micro)electrodes, biosensing platforms, or field-effect transistors, are also described.


Assuntos
Técnicas Biossensoriais , Dopamina/análise , Neurotransmissores , Carbono , Técnicas Eletroquímicas , Eletrodos , Humanos , Metais , Óxidos , Polímeros
14.
Brain Nerve ; 73(7): 829-837, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34234041

RESUMO

Parkinson's disease (PD) is a progressive neurodegenerative disorder. The major motor symptoms of PD are mainly caused by dopamine (DA) deficiency due to the loss of dopaminergic neurons in the substantia nigra. Most patients also show non-motor symptoms, such as cognitive impairment, mood disturbance, pain, and sleep disturbance. These symptoms cannot be explained by DA deficiency alone and are likely involved with other neurotransmitter systems, including glutamate, serotonin, noradrenaline, or gamma aminobutyric acid. Other neurotransmitters may have therapeutic effects on some symptoms of PD. In this review, we discuss the pathophysiology of Parkinsonian symptoms, with a focus on neurotransmitters. (Received 2 February, 2021; Accepted 16 February, 2021; Published 1 July, 2021).


Assuntos
Doença de Parkinson , Dopamina , Neurônios Dopaminérgicos , Humanos , Neurotransmissores , Substância Negra
15.
Biochemistry (Mosc) ; 86(6): 729-736, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34225595

RESUMO

Comparative analysis of available literature data on the pathogenetic neuroendocrine mechanisms of depression and post-traumatic stress disorder (PTSD) is provided in this review to identify their common features and differences. We discuss the multidirectional modifications of the activity of cortical and subcortical structures of the brain, levels of neurotransmitters and their receptors, and functions of the hypothalamic-pituitary-adrenocortical axis in depression and PTSD. The analysis shows that these disorders are examples of opposite failures in the system of adaptive stress response of the body to stressful psychotraumatic events. On this basis, it is concluded that the currently widespread use of similar approaches to treat these disorders is not justified, despite the significant similarity of their anxiety-depressive symptoms; development of differential therapeutic strategies is required.


Assuntos
Encéfalo/metabolismo , Transtorno Depressivo Maior/metabolismo , Glucocorticoides/metabolismo , Neurotransmissores/metabolismo , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtorno Depressivo Maior/etiologia , Humanos , Transtornos de Estresse Pós-Traumáticos/etiologia , Estresse Psicológico
16.
Nutrients ; 13(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205336

RESUMO

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota-gut-brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.


Assuntos
Cognição/fisiologia , Microbioma Gastrointestinal/fisiologia , Doenças Neurodegenerativas/microbiologia , Neurotransmissores/fisiologia , Doença de Alzheimer/microbiologia , Animais , Ansiedade/microbiologia , Transtorno do Espectro Autista/microbiologia , Encéfalo/fisiopatologia , Depressão/microbiologia , Disbiose/fisiopatologia , Humanos , Doença de Parkinson/microbiologia , Esquizofrenia/microbiologia
17.
Int J Mol Sci ; 22(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34281235

RESUMO

Multiple sclerosis (MS) is a demyelinating, autoimmune disease that affects a large number of young adults. Novel therapies for MS are needed considering the efficiency and safety limitations of current treatments. In our study, we investigated the effects of venlafaxine (antidepressant, serotonin-norepinephrine reuptake inhibitor), risperidone (atypical antipsychotic) and febuxostat (gout medication, xanthine oxidase inhibitor) in the cuprizone mouse model of acute demyelination, hypothesizing an antagonistic effect on TRPA1 calcium channels. Cuprizone and drugs were administered to C57BL6/J mice for five weeks and locomotor activity, motor performance and cold sensitivity were assessed. Mice brains were harvested for histological staining and assessment of oxidative stress markers. Febuxostat and metabolites of venlafaxine (desvenlafaxine) and risperidone (paliperidone) were tested for TRPA1 antagonistic activity. Following treatment, venlafaxine and risperidone significantly improved motor performance and sensitivity to a cold stimulus. All administered drugs ameliorated the cuprizone-induced deficit of superoxide dismutase activity. Desvenlafaxine and paliperidone showed no activity on TRPA1, while febuxostat exhibited agonistic activity at high concentrations. Our findings indicated that all three drugs offered some protection against the effects of cuprizone-induced demyelination. The agonistic activity of febuxostat can be of potential use for discovering novel TRPA1 ligands.


Assuntos
Febuxostat/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Neurotransmissores/uso terapêutico , Risperidona/uso terapêutico , Cloridrato de Venlafaxina/uso terapêutico , Animais , Corpo Caloso/efeitos dos fármacos , Cuprizona , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Febuxostat/farmacologia , Feminino , Células HEK293 , Humanos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Neurotransmissores/farmacologia , Risperidona/farmacologia , Canal de Cátion TRPA1/efeitos dos fármacos , Cloridrato de Venlafaxina/farmacologia
18.
Nat Commun ; 12(1): 4251, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253733

RESUMO

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder characterized by deficient synthesis of dopamine and serotonin. It presents in early infancy, and causes severe developmental disability and lifelong motor, behavioral, and autonomic symptoms including oculogyric crises (OGC), sleep disorder, and mood disturbance. We investigated the safety and efficacy of delivery of a viral vector expressing AADC (AAV2-hAADC) to the midbrain in children with AADC deficiency (ClinicalTrials.gov Identifier NCT02852213). Seven (7) children, aged 4-9 years underwent convection-enhanced delivery (CED) of AAV2-hAADC to the bilateral substantia nigra (SN) and ventral tegmental area (VTA) (total infusion volume: 80 µL per hemisphere) in 2 dose cohorts: 1.3 × 1011 vg (n = 3), and 4.2 × 1011 vg (n = 4). Primary aims were to demonstrate the safety of the procedure and document biomarker evidence of restoration of brain AADC activity. Secondary aims were to assess clinical improvement in symptoms and motor function. Direct bilateral infusion of AAV2-hAADC was safe, well-tolerated and achieved target coverage of 98% and 70% of the SN and VTA, respectively. Dopamine metabolism was increased in all subjects and FDOPA uptake was enhanced within the midbrain and the striatum. OGC resolved completely in 6 of 7 subjects by Month 3 post-surgery. Twelve (12) months after surgery, 6/7 subjects gained normal head control and 4/7 could sit independently. At 18 months, 2 subjects could walk with 2-hand support. Both the primary and secondary endpoints of the study were met. Midbrain gene delivery in children with AADC deficiency is feasible and safe, and leads to clinical improvements in symptoms and motor function.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Erros Inatos do Metabolismo dos Aminoácidos/terapia , Descarboxilases de Aminoácido-L-Aromático/deficiência , Dependovirus/genética , Neurônios Dopaminérgicos/metabolismo , Técnicas de Transferência de Genes , Terapia Genética , Imageamento por Ressonância Magnética , Mesencéfalo/patologia , Erros Inatos do Metabolismo dos Aminoácidos/líquido cefalorraquidiano , Erros Inatos do Metabolismo dos Aminoácidos/fisiopatologia , Descarboxilases de Aminoácido-L-Aromático/líquido cefalorraquidiano , Descarboxilases de Aminoácido-L-Aromático/genética , Criança , Pré-Escolar , Discinesias/fisiopatologia , Feminino , Terapia Genética/efeitos adversos , Humanos , Masculino , Metaboloma , Atividade Motora , Neurotransmissores/líquido cefalorraquidiano , Neurotransmissores/metabolismo , Fatores de Tempo
19.
Int J Mol Sci ; 22(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204780

RESUMO

The risk of accidental bromine (Br2) exposure to the public has increased due to its enhanced industrial use. Inhaled Br2 damages the lungs and the heart; however, adverse effects on the brain are unknown. In this study, we examined the neurological effects of inhaled Br2 in Sprague Dawley rats. Rats were exposed to Br2 (600 ppm for 45 min) and transferred to room air and cage behavior, and levels of glial fibrillary acidic protein (GFAP) in plasma were examined at various time intervals. Bromine exposure resulted in abnormal cage behavior such as head hitting, biting and aggression, hypervigilance, and hyperactivity. An increase in plasma GFAP and brain 4-hydroxynonenal (4-HNE) content also was observed in the exposed animals. Acute and delayed sympathetic nervous system activation was also evaluated by assessing the expression of catecholamine biosynthesizing enzymes, tryptophan hydroxylase (TrpH1 and TrpH2), and tyrosine hydroxylase (TyrH), along with an assessment of catecholamines and their metabolites. TyrH was found to be increased in a time-dependent manner. TrpH1 and TrpH2 were significantly decreased upon Br2 exposure in the brainstem. The neurotransmitter content evaluation indicated an increase in 5-HT and dopamine at early timepoints after exposure; however, other metabolites were not significantly altered. Taken together, our results predict brain damage and autonomic dysfunction upon Br2 exposure.


Assuntos
Comportamento Animal , Tronco Encefálico/patologia , Bromo/administração & dosagem , Bromo/efeitos adversos , Neurônios/patologia , Estresse Oxidativo , Administração por Inalação , Animais , Biomarcadores/metabolismo , Lesões Encefálicas/patologia , Catecolaminas/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Metaboloma , Neurônios/efeitos dos fármacos , Neurotransmissores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Triptofano Hidroxilase/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
20.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208199

RESUMO

Thus far, many hypotheses have been proposed explaining the cause of depression. Among the most popular of these are: monoamine, neurogenesis, neurobiology, inflammation and stress hypotheses. Many studies have proven that neurogenesis in the brains of adult mammals occurs throughout life. The generation of new neurons persists throughout adulthood in the mammalian brain due to the proliferation and differentiation of adult neural stem cells. For this reason, the search for drugs acting in this mechanism seems to be a priority for modern pharmacotherapy. Paroxetine is one of the most commonly used antidepressants. However, the exact mechanism of its action is not fully understood. The fact that the therapeutic effect after the administration of paroxetine occurs after a few weeks, even if the levels of monoamine are rapidly increased (within a few minutes), allows us to assume a neurogenic mechanism of action. Due to the confirmed dependence of depression on serotonin, norepinephrine, dopamine and γ-aminobutyric acid levels, studies have been undertaken into paroxetine interactions with these primary neurotransmitters using in silico and in vitro methods. We confirmed that paroxetine interacts most strongly with monoamine transporters and shows some interaction with γ-aminobutyric acid transporters. However, studies of the potency inhibitors and binding affinity values indicate that the neurogenic mechanism of paroxetine's action may be determined mainly by its interactions with serotonin transporters.


Assuntos
Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Paroxetina/metabolismo , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Animais , Sítios de Ligação , Células CHO , Cricetulus , Humanos , Simulação de Acoplamento Molecular , Neurotransmissores/química , Neurotransmissores/metabolismo , Paroxetina/química
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