RESUMO
OBJECTIVE: In this paper, we aimed at reviewing evidence-based treatment options for bipolar mania and proposed tentative evidence-based clinical suggestions regarding the management of a manic episode, especially regarding the choice of the proper mood stabilizer and antipsychotic medication. METHOD: A narrative review was undertaken addressing 'treatment of bipolar mania'. Findings have been synthesized and incorporated with clinical experience into a model to support different treatment choices. RESULTS: To date, there is solid evidence supporting the use of several medications, such as lithium, divalproex, and carbamazepine, and antipsychotics, such as chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, inhaled loxapine, asenapine, and cariprazine in acute mania, and some evidence supporting the use of clozapine or electroconvulsive therapy in treatment-refractory cases. However, in clinical practice, when making decisions about treatment, personalized treatment is needed, according to the different clinical presentations and more complex clinical situations within the manic episode and considering a long-term view and with the objective of not only a symptomatic but also functional recovery. After remission from acute mania, psychoeducation strategies are useful to ensure adherence. DISCUSSION: Despite the evidence forefficacy of many currently available treatments for mania, the majority of RCTs provide little direction for the clinician as to what steps might be optimal in different presentations of mania as well as in the presence of specific patient characteristics. Manic episodes should be managed on a personalized basis considering the clinical course and patient criteria and with the expectation of maintaining that treatment in the long-term.
Assuntos
Antipsicóticos , Transtorno Bipolar , Clozapina , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Clozapina/uso terapêutico , Humanos , Mania , Olanzapina/uso terapêuticoRESUMO
We report that the apical dendrites of CA3 hippocampal pyramidal neurons are increased during labor and birth in the valproate model of autism but not in control animals. Using the iDISCO clearing method, we show that hippocampal, especially CA3 region, and neocortical volumes are increased and that the cerebral volume distribution shifts from normal to lognormal in valproate-treated animals. Maternal administration during labor and birth of the NKCC1 chloride transporter antagonist bumetanide, which reduces [Cl-]i levels and attenuates the severity of autism, abolished the neocortical and hippocampal volume changes and reduced the whole-brain volume in valproate-treated animals. These results suggest that the abolition of the oxytocin-mediated excitatory-to-inhibitory shift of GABA actions during labor and birth contributes to the pathogenesis of autism spectrum disorders by stimulating growth during a vulnerable period.
Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/fisiopatologia , Bumetanida/uso terapêutico , Hipocampo/metabolismo , Parto/metabolismo , Células Piramidais/metabolismo , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Animais , Animais Recém-Nascidos , Transtorno do Espectro Autista/induzido quimicamente , Dendritos/efeitos dos fármacos , Dendritos/metabolismo , Modelos Animais de Doenças , Feminino , GABAérgicos/farmacologia , Gravidez , Células Piramidais/efeitos dos fármacos , Ratos , Ratos Wistar , Ácido Valproico/farmacologiaRESUMO
We report that half striatal cholinergic interneurons are dual transmitter cholinergic and GABAergic interneurons (CGINs) expressing ChAT, GAD65, Lhx7, and Lhx6 mRNAs, labeled with GAD and VGAT, generating monosynaptic dual cholinergic/GABAergic currents and an inhibitory pause response. Dopamine deprivation increases CGINs ongoing activity and abolishes GABAergic inhibition including the cortico-striatal pause because of high [Cl-]i levels. Dopamine deprivation also dramatically increases CGINs dendritic arbors and monosynaptic interconnections probability, suggesting the formation of a dense CGINs network. The NKCC1 chloride importer antagonist bumetanide, which reduces [Cl-]i levels, restores GABAergic inhibition, the cortico-striatal pause-rebound response, and attenuates motor effects of dopamine deprivation. Therefore, most of the striatal cholinergic excitatory drive is balanced by a concomitant powerful GABAergic inhibition that is impaired by dopamine deprivation. The attenuation by bumetanide of cardinal features of Parkinson's disease paves the way to a novel therapeutic strategy based on a restoration of low [Cl-]i levels and GABAergic inhibition.
Assuntos
Neurônios Colinérgicos/metabolismo , Corpo Estriado/metabolismo , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Interneurônios/metabolismo , Doença de Parkinson Secundária/metabolismo , Ácido gama-Aminobutírico/metabolismo , Acetilcolina/metabolismo , Acetilcolina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Bumetanida/farmacologia , Cloretos/metabolismo , Colinérgicos/metabolismo , Colinérgicos/farmacologia , Neurônios Colinérgicos/efeitos dos fármacos , Neurônios Colinérgicos/patologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Dopamina/deficiência , Regulação da Expressão Gênica , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Humanos , Interneurônios/efeitos dos fármacos , Interneurônios/patologia , Transporte de Íons , Proteínas com Homeodomínio LIM/genética , Proteínas com Homeodomínio LIM/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Doença de Parkinson Secundária/genética , Doença de Parkinson Secundária/patologia , Técnicas de Patch-Clamp , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia , Membro 2 da Família 12 de Carreador de Soluto/genética , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/genética , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo , Ácido gama-Aminobutírico/farmacologiaRESUMO
Progress in elucidating the molecular and cellular pathophysiology of neuropsychiatric disorders has been hindered by the limited availability of living human brain tissue. The emergence of induced pluripotent stem cells (iPSCs) has offered a unique alternative strategy using patient-derived functional neuronal networks. However, methods for reliably generating iPSC-derived neurons with mature electrophysiological characteristics have been difficult to develop. Here, we report a simplified differentiation protocol that yields electrophysiologically mature iPSC-derived cortical lineage neuronal networks without the need for astrocyte co-culture or specialized media. This protocol generates a consistent 60:40 ratio of neurons and astrocytes that arise from a common forebrain neural progenitor. Whole-cell patch-clamp recordings of 114 neurons derived from three independent iPSC lines confirmed their electrophysiological maturity, including resting membrane potential (-58.2±1.0 mV), capacitance (49.1±2.9 pF), action potential (AP) threshold (-50.9±0.5 mV) and AP amplitude (66.5±1.3 mV). Nearly 100% of neurons were capable of firing APs, of which 79% had sustained trains of mature APs with minimal accommodation (peak AP frequency: 11.9±0.5 Hz) and 74% exhibited spontaneous synaptic activity (amplitude, 16.03±0.82 pA; frequency, 1.09±0.17 Hz). We expect this protocol to be of broad applicability for implementing iPSC-based neuronal network models of neuropsychiatric disorders.
Assuntos
Técnicas de Cultura de Células/métodos , Diferenciação Celular/fisiologia , Neurogênese/fisiologia , Potenciais de Ação/fisiologia , Astrócitos/fisiologia , Células Cultivadas , Técnicas de Cocultura , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Redes Neurais de Computação , Células-Tronco Neurais/fisiologia , Neurônios/fisiologia , Técnicas de Patch-Clamp/métodosRESUMO
Memories are encoded within sparsely distributed neuronal ensembles. However, the defining cellular properties of neurons within a memory trace remain incompletely understood. Using a fluorescence-based Arc reporter, we were able to visually identify the distinct subset of lateral amygdala (LA) neurons activated during auditory fear conditioning. We found that Arc-expressing neurons have enhanced intrinsic excitability and are preferentially recruited into newly encoded memory traces. Furthermore, synaptic potentiation of thalamic inputs to the LA during fear conditioning is learning-specific, postsynaptically mediated and highly localized to Arc-expressing neurons. Taken together, our findings validate the immediate-early gene Arc as a molecular marker for the LA neuronal ensemble recruited during fear learning. Moreover, these results establish a model of fear memory formation in which intrinsic excitability determines neuronal selection, whereas learning-related encoding is governed by synaptic plasticity.
Assuntos
Complexo Nuclear Basolateral da Amígdala/metabolismo , Condicionamento Clássico/fisiologia , Proteínas do Citoesqueleto/metabolismo , Medo/fisiologia , Memória/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Estimulação Acústica/efeitos adversos , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Complexo Nuclear Basolateral da Amígdala/citologia , Estimulantes do Sistema Nervoso Central/farmacologia , Colina O-Acetiltransferase/metabolismo , Proteínas do Citoesqueleto/genética , Glutamato Descarboxilase/metabolismo , Técnicas In Vitro , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Neurônios/fisiologia , Técnicas de Patch-Clamp , Fosfopiruvato Hidratase/metabolismo , Picrotoxina/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismoRESUMO
The authors present four cases. The first case is a diaphragmatic-mediastinal, the second one is a cervical-mediastinal one, the third case has a buttock, the last one is a case of hip-thigh. Their ages are one, eight and three years old and the fourth case is seven days old. They appear in axilla, neck, thoracic wall and fat prevertebral tissue, in below three year old children. Despite their benignity, the tumors grow very fast. The complete extirpation is fundamental to avoid relapses, which are presented approximately in a 15 for 100 of the cases. Mutilations are not necessary, since it is a benign tumor. Finally, the authors amply review the literature. They differentiate the concepts of lipoma, hibernoma and lipoblastoma.