RESUMO
In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression.
Assuntos
Depressão/tratamento farmacológico , Ácido Láctico/farmacologia , Animais , Antidepressivos/farmacologia , Astrócitos , Transtorno Depressivo Maior/tratamento farmacológico , Modelos Animais de Doenças , Hipocampo/metabolismo , Ácido Láctico/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Neurônios , Transdução de Sinais/efeitos dos fármacosRESUMO
This corrects the article DOI: 10.1038/mp.2016.179.
RESUMO
A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte-neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine.
Assuntos
Astrócitos/metabolismo , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Ácido Láctico/metabolismo , Tonsila do Cerebelo/metabolismo , Animais , Arabinose , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Transporte/metabolismo , Cocaína/farmacologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Psicológico , Sinais (Psicologia) , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Imino Furanoses , Masculino , Proteínas de Membrana/metabolismo , Memória/fisiologia , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Álcoois AçúcaresRESUMO
Food allergies are a global health issue with increasing prevalence. Allergic reactions can range from mild local symptoms to severe anaphylactic reactions. Significant progress has been made in diagnostic tools such as component-resolved diagnostics and its impact on risk stratification as well as in therapeutic approaches including biologicals. However, a cure for food allergy has not yet been achieved and patients and their families are forced to alter eating habits and social engagements, impacting their quality of life. New technologies and improved in vitro and in vivo models will advance our knowledge of the pathogenesis of food allergies and multicenter-multinational cohort studies will elucidate interactions between genetic background, lifestyle, and environmental factors. This review focuses on new insights and developments in the field of food allergy and summarizes recently published articles.
Assuntos
Hipersensibilidade Alimentar , HumanosRESUMO
House dust mites can be found all over the world where human beings live independent from the climate. Proteins from the gastrointestinal tract- almost all known as enzymes - are the allergens which induce chronic allergic diseases. The inhalation of small amounts of allergens on a regular base all night leads to a slow beginning of the disease with chronically stuffed nose and an exercise induced asthma which later on persists. House dust mites grow well in a humid climate - this can be in well isolated dwellings or in the tropical climate - and nourish from human skin dander. Scales are found in mattresses, upholstered furniture and carpets. The clinical picture with slowly aggravating complaints leads quite often to a delayed diagnosis, which is accidently done on the occasion of a wider spectrum of allergy skin testing. The beginning of a medical therapy with topical steroids as nasal spray or inhalation leads to a fast relief of the complaints. Although discussed in extensive controversies in the literature - at least in Switzerland with the cold winter and dry climate - the recommendation of house dust mite avoidance measures is given to patients with good clinical results. The frequent ventilation of the dwelling with cold air in winter time cause a lower indoor humidity. Covering encasings on mattresses, pillow, and duvets reduces the possibility of chronic contact with mite allergens as well as the weekly changing the bed linen. Another option of therapy is the specific immunotherapy with extracts of house dust mites showing good results in children and adults. Using recombinant allergens will show a better quality in diagnostic as well as in therapeutic specific immunotherapy.
Assuntos
Pyroglyphidae/imunologia , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/imunologia , Adolescente , Corticosteroides/administração & dosagem , Animais , Especificidade de Anticorpos/imunologia , Testes de Provocação Brônquica , Terapia Combinada , Dermatophagoides farinae/imunologia , Dermatophagoides pteronyssinus/imunologia , Dessensibilização Imunológica , Zeladoria , Humanos , Imunoglobulina E/sangue , Testes Intradérmicos , Masculino , Rinite Alérgica Perene/terapiaRESUMO
This article presents and validates a novel algorithm for the continuous monitoring of the VO2 during exercise. The algorithm relies on instantaneous HR measurements to provide a continuous estimation, and can be integrated in a wearable device (e.g., smartwatch, sensor patch). It can be customized by user's main anthropomorphic parameters and automatically learns from newly incoming data recalibrating itself if needed. The system is evaluated against a database of 14 healthy subjects performing various maximal endurance tests. The proposed method provides a VO2 estimation with average RMSE of 4.63 ml/kg/min.