ABSTRACT
Sympathetic arborizations act as the essential efferent signals in regulating the metabolism of peripheral organs including white adipose tissues (WAT). However, whether these local neural structures would be of plastic nature, and how such plasticity might participate in specific metabolic events of WAT, remains largely uncharacterized. In this study, we exploit the new volume fluorescence-imaging technique to observe the significant, and also reversible, plasticity of intra-adipose sympathetic arborizations in mouse inguinal WAT in response to cold challenge. We demonstrate that this sympathetic plasticity depends on the cold-elicited signal of nerve growth factor (NGF) and TrkA receptor. Blockage of NGF or TrkA signaling suppresses intra-adipose sympathetic plasticity, and moreover, the cold-induced beiging process of WAT. Furthermore, we show that NGF expression in WAT depends on the catecholamine signal in cold challenge. We therefore reveal the key physiological relevance, together with the regulatory mechanism, of intra-adipose sympathetic plasticity in the WAT metabolism.
Subject(s)
Animals , Mice , Adipose Tissue, Beige , Cell Biology , Diagnostic Imaging , Metabolism , Catecholamines , Metabolism , Cold Temperature , Imaging, Three-Dimensional , Nerve Growth Factor , Metabolism , Neuronal Plasticity , Receptor, trkA , Metabolism , Signal Transduction , Sympathetic Nervous System , PhysiologyABSTRACT
O camundongo não obeso diabético (NOD) é caracterizado por desenvolver naturalmente diabetes mellitus tipo 1 (DM-1) com similaridade ao diabetes mellitus tipo 1 em humanos. A manifestação espontânea do diabetes neste modelo animal é caracterizado por infiltração progressiva das ilhotas de Langerhans por células mononucleares linfócitos T (CD4+ e CD8+) e destruição das células ß pancreáticas produtoras de insulina. O fator de crescimento neural (NGF) e algumas citocinas estão associados a regeneração neural, além de atuarem sobre células do sistema imune. Em adição a estes efeitos, NGF age na liberação de insulina pelas células betas das ilhotas pancreáticas, tornando-se foco de interesse com relação as suas propriedades moduladoras no processo inflamatório na ilhota pancreática. O gangliosídeo GM1 liga-se ao receptor de alta afinidade (TrkA) do NGF-ß, mimetizando seus efeitos. No presente trabalho, avaliamos a ação modulatória de GM1 e NGF em cultura de ilhotas pancreáticas, provenientes de camundongos NOD. Foram avaliados por meio de RT-PCR a expressão gênica de NGF-ß, TrkA e insulina e, por ensaio imunoenzimático, a concentração de citocinas IL-1ß, IL-12, TNF-a, INF-y e insulina. Nossos resultados sugerem ação moduladora similar entre GM1 e NGF sobre as ilhotas de NOD não diabéticos e pré-diabéticos. NGF e GM1 aumentam a expressão gênica de NGF e TrkA e diminuem a expressão gênica de insulina em NOD não diabéticos e pré-diabéticos. Além disso, aumentam a liberação de insulina e diminui a de citocinas inflamatórias IL-1ß, IL-12, TNF-a, IFN-y que caracterizam a resposta Th1.
The non-obese diabetic mice (NOD) lineage is characterized by developing type 1 diabetes mellitus (DM-1) naturally, bearing a similarity to DM-1 in human beings. The spontaneous manifestation of diabetes is characterized by gradual infiltration in pancreatic islets by mononuclear cells lymphocytes T (CD4+ and CD8+) and destruction of the ß-cells producers of insulin. One consequence of this effect, is the release of neurotrophins trying modulate the insulin release by the ß cells of pancreatic islets. Thus, the neurotrophins have been the focus of interest in the modulation of the inflammatory process in the pancreatic islets. The ganglioside GM1 binds to the high affinity receptor (TrkA) of the NGF-ß, enhancing its effect. In the present work, we evaluate the immune modulation properties of GM1 and NGF in culture of pancreatic islets from NOD mice. The gene expression of NGF-ß, TrkA and insulin for immune enzymatic assay, the concentration of cytokines IL 1ß, IL-12, TNF-a, IFN-y and insulin were evaluated by RT-PCR and ELISA. Our results suggest similar modulation action between GM1 and NGF on islets of NOD non-diabetic and pre-diabetic. GM1 and NGF action increases the gene expression of NGF and TrkA and the decrease of insulin in mice NOD non-diabetic and pre-diabetic. Moreover, GM1 and NGF increase the insulin release and decrease inflammatory cytokines that characterize the Th1 reply.
Subject(s)
Animals , Mice , Diabetes Mellitus, Type 1 , Islets of Langerhans , Mice, Inbred NOD , Transforming Growth Factors , Lymphotoxin-alpha , Receptors, Tumor Necrosis Factor , Tumor Necrosis Factor-alphaABSTRACT
@#ObjectiveTo investigate the effects of Chinese compound Sheng-wu Capsule on learning-memory ability and histology including the neurons, astrocytes and expression of nerve growth factor(NGF) and its receptor (TrkA) in hippocampus CA1 of aged rats. MethodsSheng-wu Capsule consists of 6 kinds of Chinese medicinal herbs such as polygonum multiflorum,ginseng, and Rhizoma Acori Tatarinowii.The water-soluble component of polygonum multiflorum,2,3,5,4'- tetrahydroxystibane-2-O-β-D-glucoside was the quality standard of Sheng-wu Capsule.Aged Wistar rats(22 months old) were orally administrated with Sheng-wu Capsule(1.8g/kg and 0.9g/kg) for 2 months. Positive control drug was Piracetam(0.56g/kg). The learning and memory ability was tested by passageway water maze; the number and morphology of neurons was detected by HE staining; the proliferation of astrocytes was detected by immuno-histochemistry for glial fibrillary acidic protein(GFAP); the expression of neurotrophic substance was detected by immuno-histochemistry for NGF and TrkA receptor by ABC method. Image analysis to determine average cell number, size(area) and staining density in hippocampal CA1 region was achieved by VISILOG 5.0 image pattern analyser.ResultsBoth NGF and TrkA-immunoreactive neurons in aged rats significantly decreased as well as cell number, size and staining density in CA1 region of hippocampus(P<0.01). Aged rats showed damage of neurons and increase of GFAP positive cells in the same area,model rats indicated learning-memory deficit too. In Sheng-wu Capsule administrated groups,the significant little decrease in cell number, size and staining density of NGF and TrkA-immunoreactive neurons in CA1 region of hippocampus was observed(P<0.01-0.05). The loss of Neurons and proliferation of astrocytes were inhibited and learning-memory ability was also improved in Sheng-wu groups.Conclusions Chinese compound Sheng-wu Capsule significantly promotes the expression of NGF and TrkA in aged rats and it relieves the damage of hippocampus.This may be the mechanism by which Sheng-wu Capsule improves the learning and memory ability. Enhancing endogenous neurotrophic substance plays an important role in the treatment of Alzheimer's disease.