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1.
J Biomed Opt ; 26(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33386708

RESUMO

SIGNIFICANCE: Line scanning-based temporal focusing multiphoton microscopy (TFMPM) has superior axial excitation confinement (AEC) compared to conventional widefield TFMPM, but the frame rate is limited due to the limitation of the single line-to-line scanning mechanism. The development of the multiline scanning-based TFMPM requires only eight multiline patterns for full-field uniform multiphoton excitation and it still maintains superior AEC. AIM: The optimized parallel multiline scanning TFMPM is developed, and the performance is verified with theoretical simulation. The system provides a sharp AEC equivalent to the line scanning-based TFMPM, but fewer scans are required. APPROACH: A digital micromirror device is integrated in the TFMPM system and generates the multiline pattern for excitation. Based on the result of single-line pattern with sharp AEC, we can further model the multiline pattern to find the best structure that has the highest duty cycle together with the best AEC performance. RESULTS: The AEC is experimentally improved to 1.7 µm from the 3.5 µm of conventional TFMPM. The adopted multiline pattern is akin to a pulse-width-modulation pattern with a spatial period of four times the diffraction-limited line width. In other words, ideally only four π / 2 spatial phase-shift scans are required to form a full two-dimensional image with superior AEC instead of image-size-dependent line-to-line scanning. CONCLUSIONS: We have demonstrated the developed parallel multiline scanning-based TFMPM has the multiline pattern for sharp AEC and the least scans required for full-field uniform excitation. In the experimental results, the temporal focusing-based multiphoton images of disordered biotissue of mouse skin with improved axial resolution due to the near-theoretical limit AEC are shown to clearly reduce background scattering.

2.
Cell Transplant ; 29: 963689720927394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32854518

RESUMO

Mammalian fat comprises white and brown adipose tissue (WAT and BAT, respectively). WAT stores energy, whereas BAT is used for thermogenesis. In recent years, the incidence of obesity and its associated disorders have increased tremendously. Considering the thermogenic capacity and decreased levels of BAT with increasing age, BAT can be used as a suitable therapeutic target for the treatment of obesity and diabetes. In several studies, using positron emission tomography and computed tomography images, adult humans have been shown to have functional BAT in interscapular fat. Results of these basic research studies on BAT have shed light on the new components of transcriptional regulation and the role of hormones in stimulating BAT growth and differentiation. In this review article, we have summarized the thermogenic regulators identified in the past decades by focusing on peroxisome proliferator-activated receptor gamma/uncoupling protein 1 activators, branched-chain amino acids, fatty acids (lipokine), and adenosine monophosphate-activated protein kinase mediators. We have also presented the progress of a few ongoing clinical trials aimed at the treatment of obesity and its associated metabolic disorders. The main purpose of this review was to provide a comprehensive introduction to the latest knowledge of the representative thermogenic regulators for the treatment of obesity. The fat combustion capacity of BAT may have great potential and can be considered as a suitable target for the therapeutic application of drugs from bench-to-bed treatment of obesity and the associated diseases.

3.
J Neuroinflammation ; 17(1): 210, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664974

RESUMO

BACKGROUND: Excessive microglial activation is implicated in the pathogenesis of various age-related neurodegenerative diseases. In addition to neurons, brain-derived neurotrophic factor (BDNF) and its receptor TrkB are also expressed in microglia. However, the direct effect of BDNF on age-related microglial activation has rarely been investigated. METHODS: We began to address this question by examining the effect of age on microglial activation and the BDNF-TrkB pathway in mice. By using pharmacological and genetic approaches, the roles of BDNF and downstream signaling pathways in microglial activation and related neurotoxicity were examined in microglial cell line and primary microglial cells. RESULTS: We showed that microglial activation was evident in the brains of aged mice. The levels of BDNF and TrkB in microglia decreased with age and negatively correlated with their activation statuses in mice during aging. Interestingly, aging-related microglial activation could be reversed by chronic, subcutaneous perfusion of BDNF. Peripheral lipopolysaccharide (LPS) injection-induced microglial activation could be reduced by local supplement of BDNF, while shTrkB induced local microglial activation in naïve mice. In cultured microglial cell line and primary microglial cells, BDNF inhibited LPS-induced microglial activation, including morphological changes, activations of p38, JNK, and NF-кB, and productions of proinflammatory cytokines. These effects were blocked by shTrkB. BDNF induced activations of ErK and CREB which then competed with LPS-induced activation of NF-кB for binding to a common coactivator, CREB-binding protein. CONCLUSIONS: Decreasing BDNF-TrkB signaling during aging favors microglial activation, while upregulation BDNF signaling inhibits microglial activation via the TrkB-Erk-CREB pathway.

4.
BMC Neurosci ; 20(1): 33, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291887

RESUMO

BACKGROUND: Hypothalamic inflammation including astrogliosis and microglia activation occurs after intake of high fat diet (HFD) in rodent models or in obese individuals. However, the effect of chronic HFD feeding on oligodendrocytes (OLGs), a myelin-producing glial population in the central nervous system (CNS), remains unclear. In this study, we used 8-week old male C57BL/6 mice fed by HFD for 3-6 months to induce chronic obesity. RESULTS: The transmission electron microscopy imaging analysis showed that the integrity of hypothalamic myelin was disrupted after HFD feeding for 4 and 6 months. Moreover, the accumulation of Iba1+-microglia with an amoeboid hypertrophic form was continually observed in arcuate nucleus of HFD-fed mice during the entire feeding time period. Interleukin-33 (IL-33), a tissue alarmin upon injury to the CNS, was detected with an increased level in hypothalamus after HFD feeding for 3 and 4 months. Furthermore, the in vitro study indicated that exposure of mature OLGs to IL-33 impaired OLG cell structure along with a decline in the expression of myelin basic protein. CONCLUSIONS: Altogether, our findings demonstrate that chronic HFD feeding triggers hypothalamic myelin disruption in accompany with IL-33 upregulation and prolonged microglial activation in hypothalamus. Given that the addition of exogenous IL-33 was harmful for the maturation of OLGs, an increase in IL-33 by chronic HFD feeding might contribute to the induction of hypothalamic myelin disruption.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Hipotálamo/metabolismo , Interleucina-33/metabolismo , Bainha de Mielina/patologia , Regulação para Cima , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Núcleo Arqueado do Hipotálamo/patologia , Hipotálamo/patologia , Masculino , Camundongos , Proteína Básica da Mielina/biossíntese , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Cultura Primária de Células , Ratos , Fatores de Tempo
5.
Brain Struct Funct ; 224(8): 2677-2689, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31352506

RESUMO

Acute and long-term exercise differentially affect brain functions. It has been suggested that neuronal activation is one of the mechanisms for exercise-induced enhancement of brain functions. However, the differential effects of acute and long-term exercise on the spatial and temporal profiles of neuronal activation in the brain have been scarcely explored. In this study, we profiled the expression of c-Fos, a marker of neuronal activation, in selected 26 brain regions of 2-month-old male C57/B6 mice that received either a single bout of treadmill running (acute exercise) or a 4-week treadmill training (long-term exercise) at the same duration (1 h/day) and intensity (10 m/min). The c-Fos expression was determined before, immediately after, and 2 h after the run. The results showed that acute exercise increased the densities of c-Fos+ cells in the ventral hippocampal CA1 region, followed by (in a high to low order) the primary somatosensory cortex, other hippocampal subregions, and striatum immediately after the run; significant changes remained evident in the hippocampal subregions after a 2-h rest. Long-term exercise increased the densities of c-Fos+ cells in the striatum, followed by the primary somatosensory, primary and secondary motor cortices, hippocampal subregions, hypothalamic nuclei, and lateral periaqueductal gray; significant changes remained evident in the striatum, hippocampal subregions, hypothalamic nuclei, and lateral periaqueductal gray after a 2-h rest. Interestingly, the densities of c-Fos+ cells in the substantia nigra and ventral tegmental area only increased after a 2-h rest after the run in the long-term exercise group. The densities of c-Fos+ cells were positively correlated with the expression of brain-derived neurotrophic factor in the selected brain regions. In conclusion, both acute and long-term treadmill running at mild intensity induce c-Fos expression in the limbic system and movement-associated cortical and subcortical regions, with long-term exercise involving more brain regions (i.e., hypothalamus and periaqueductal gray) and longer lasting effects.


Assuntos
Encéfalo/metabolismo , Atividade Motora/fisiologia , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Corrida , Fatores de Tempo
6.
Nutrients ; 11(1)2018 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-30583503

RESUMO

There has been increasing evidence that consumption of dietary supplements or specific nutrients can influence cognitive processes and emotions. A proprietary chicken meat extraction, Chicken Meat Ingredient-168 (CMI-168), has previously been shown to enhance cognitive function in humans. However, the mechanism underlying the CMI-168-induced benefits remains unclear. In this study, we investigated the effects of CMI-168 on hippocampal neuroplasticity and memory function in middle-aged (9⁻12 months old) mice. The mice in the test group (termed the "CMI-168 group") were fed dietary pellets produced by mixing CMI-168 and normal laboratory mouse chow to provide a daily CMI-168 dose of 150 mg/kg of body weight for 6 weeks. The control mice (termed the "Chow group") were fed normal laboratory mouse chow pellets. CMI-168 supplementation did not affect the body weight gain, food intake, or exploratory behavior of the mice. In the novel object recognition test, the CMI-168 group showed better hippocampus-related non-spatial memory compared to the control Chow group. However, spatial memory examined by the Morris Water Maze test was similar between the two groups. There was also no significant difference in the induction and maintenance of long-term potentiation and dendritic complexity of the hippocampal cornu ammonis region 1 (CA1) neurons, as well as the levels of neuroplasticity-related proteins in the hippocampi of the CMI-168 and Chow groups. Interestingly, we observed that CMI-168 appeared to protect the mice against stress-induced weight loss. In conclusion, dietary supplementation of CMI-168 was found to improve learning and memory in middle-aged mice, independent of structural or functional changes in the hippocampus. The resilience to stress afforded by CMI-168 warrants further investigation.


Assuntos
Galinhas , Aprendizagem/fisiologia , Produtos da Carne , Memória/fisiologia , Envelhecimento , Animais , Suplementos Nutricionais , Manipulação de Alimentos/métodos , Hipocampo/química , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Aprendizagem/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Produtos da Carne/análise , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/análise , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Neurônios/citologia
7.
Brain Plast ; 4(1): 95-110, 2018 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-30564549

RESUMO

Accumulating evidence indicates that exercise can improve learning and memory as well as attenuate neurodegeneration, including Alzheimer's disease (AD). In addition to improving neuroplasticity by altering the synaptic structure and function in various brain regions, exercise also modulates systems like angiogenesis and glial activation that are known to support neuroplasticity. Moreover, exercise helps to maintain a cerebral microenvironment that facilitates synaptic plasticity by enhancing the clearance of Aß, one of the main culprits of AD pathogenesis. The purpose of this review is to highlight the positive impacts of exercise on promoting neuroplasticity. Possible mechanisms involved in exercise-modulated neuroplasticity are also discussed. Undoubtedly, more studies are needed to design an optimal personalized exercise protocol for enhancing brain function.

8.
Brain Res ; 1700: 66-77, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30009766

RESUMO

Metabolic disorders induce adverse effects on brain functions. The hippocampus is one of the most vulnerable regions to metabolic disorders. Disrupted neuroplasticity is a major cause of hippocampus-related behavioral impairments, including memory loss, anxiety, and depression. Astrocytes support processes of neuroplasticity. However, whether metabolic disorders induce changes in astrocytes and their roles in affective disorders is relatively unclear. To answer this question, we fed 8-week-old male C57BL/6 mice with a high-fat diet (HFD) for 12 weeks to induce metabolic disruption and then examined their performance of hippocampus-related memory, and anxiety- and depression-like behaviors. The morphology of astrocytes and the expression of astrocytic neuroplasticity-related proteins in the hippocampus were also assessed. The results showed that HFD led to obesity, systemic insulin resistance and dysregulated lipid metabolism in mice. HFD induced depression-like behaviors, but not anxiety or memory impairment. Furthermore, HFD increased the expression of GFAP, shortened the processes of GFAP+ cells, and downregulated the expression of astrocytic neuroplasticity-related protein, GLAST, GLT-1, and connexin-43 in the hippocampi. In conclusion, HFD disturbs the function of hippocampal astrocytes and induces depression-like behaviors in mice. A decrease of hippocampal glutamate transporters may play a critical role in the pathogenesis of metabolic disorder-related depression.


Assuntos
Sistema X-AG de Transporte de Aminoácidos/metabolismo , Dieta Hiperlipídica/efeitos adversos , Hipocampo/metabolismo , Hipocampo/patologia , Neuroglia/metabolismo , Neuroglia/patologia , Animais , Depressão/etiologia , Depressão/metabolismo , Depressão/patologia , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Doenças Metabólicas/psicologia , Camundongos Endogâmicos C57BL , Distribuição Aleatória
9.
Cell Transplant ; 27(11): 1581-1587, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29991279

RESUMO

Although the clinical application of new drugs has been shown to be effective in slowing disease progression and improving the quality of life in patients with pulmonary fibrosis, the damaged lung tissue does not recover with these drugs. Thus, there is an urgent need to establish regenerative therapy, such as stem cell therapy or tissue engineering. Moreover, the clinical application of mesenchymal stem cell (MSC) therapy has been shown to be safe in humans with idiopathic pulmonary fibrosis (IPF). It seems that a combination of MSC transplantation and pharmaceutical therapy might have additional benefits; however, the experimental design for its efficacy is still lacking. In this review, we provide an overview of the mechanisms that were identified when IPF was treated with MSC transplantation or new drugs. To maximize the therapeutic effect, we suggest that MSC transplantation is combined with drug application for synergistic effects. This review provides clinicians and scientists with the most efficient medical options, in the hope that this will spur on future research and lead to an eventual cure for this disease.

10.
Neuroendocrinology ; 107(2): 147-157, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29920496

RESUMO

BACKGROUND: The notion that exposure to chronic stress predisposes individuals to developing type 2 diabetes (T2D) has gained much attention in recent decades. Long-term stress induces neuroadaptation in the amygdala and increases corticosterone levels. Corticosterone, the major stress hormone in rodents, induces insulin resistance and obesity in mice. However, little is known about whether the stress-induced amygdalar neuroadaptation could promote the risk of T2D. METHODS: We used an 11-week high-fat diet (HFD) feeding paradigm to induce insulin dysfunction in mice, followed by implementation of a 10-day social defeat (SD) stress protocol. RESULTS: Mice receiving SD at the beginning of the HFD feeding aggravated HFD-induced insulin resistance and white adipose tissue expansion. HFD mice had higher levels of plasma corticosterone, which was not affected by the SD. The SD stress upregulated the expression of TrkB and synaptotagmin-4 in the amygdala of HFD mice. Bilateral lesions of the central amygdalae before SD stress inhibited the stress-induced aggravating effect without affecting the HFD-induced elevation of plasma corticosterone. CONCLUSIONS: Stress aggravates HFD-induced insulin resistance and neuroadaptation in the amygdala. The HFD-induced insulin resistance is amygdala-dependent. Understanding the role of stress-induced amygdalar adaptation in the development of T2D could inform therapies aimed at reducing chronic stressors to decrease the risk for T2D.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Resistência à Insulina/fisiologia , Plasticidade Neuronal/fisiologia , Estresse Psicológico/fisiopatologia , Animais , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
11.
Materials (Basel) ; 11(5)2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29735937

RESUMO

The spontaneous vertical alignment of liquid crystals (LCs) in gelator (12-hydroxystearic acid)-doped LC cells was studied. Gelator-induced alignment can be used in both positive and negative LC cells. The electro-optical characteristics of the gelator-doped negative LC cell were similar to those of an LC cell that contained a vertically aligned (VA) host. The rise time of the gelator-doped LC cell was two orders of magnitude shorter than that of the VA host LC cell. The experimental results indicate that the gelator-induced vertical alignment of LC molecules occurred not only on the surface of the indium tin oxide (ITO) but also on the homogeneous alignment layer. Various LC alignments (planar, hybrid, multistable hybrid, and vertical alignments) were achieved by modulating the doped gelator concentrations. The multistable characteristic of LCs doped with the gelator is also presented. The alignment by doping with a gelator reduces the manufacturing costs and provides a means of fabricating fast-responding, flexible LC displays using a low-temperature process.

12.
Gerontology ; 64(6): 551-561, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29734165

RESUMO

BACKGROUND: Aging impairs hippocampal neuroplasticity and hippocampus-related learning and memory. In contrast, exercise training is known to improve hippocampal neuronal function. However, whether exercise is capable of restoring memory function in old animals is less clear. OBJECTIVE: Here, we investigated the effects of exercise on the hippocampal neuroplasticity and memory functions during aging. METHODS: Young (3 months), middle-aged (9-12 months), and old (18 months) mice underwent moderate-intensity treadmill running training for 6 weeks, and their hippocampus-related learning and memory, and the plasticity of their CA1 neurons was evaluated. RESULTS: The memory performance (Morris water maze and novel object recognition tests), and dendritic complexity (branch and length) and spine density of their hippocampal CA1 neurons decreased as their age increased. The induction and maintenance of high-frequency stimulation-induced long-term potentiation in the CA1 area and the expressions of neuroplasticity-related proteins were not affected by age. Treadmill running increased CA1 neuron long-term potentiation and dendritic complexity in all three age groups, and it restored the learning and memory ability in middle-aged and old mice. Furthermore, treadmill running upregulated the hippocampal expressions of brain-derived neurotrophic factor and monocarboxylate transporter-4 in middle-aged mice, glutamine synthetase in old mice, and full-length TrkB in middle-aged and old mice. CONCLUSION: The hippocampus-related memory function declines from middle age, but long-term moderate-intensity running effectively increased hippocampal neuroplasticity and memory in mice of different ages, even when the memory impairment had progressed to an advanced stage. Thus, long-term, moderate intensity exercise training might be a way of delaying and treating aging-related memory decline.


Assuntos
Envelhecimento , Hipocampo , Transtornos da Memória , Memória/fisiologia , Atividade Motora/fisiologia , Envelhecimento/fisiologia , Envelhecimento/psicologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Glutamato-Amônia Ligase/metabolismo , Hipocampo/fisiologia , Hipocampo/fisiopatologia , Aprendizagem em Labirinto , Glicoproteínas de Membrana/metabolismo , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Transtornos da Memória/prevenção & controle , Transtornos da Memória/psicologia , Camundongos , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/metabolismo , Neurônios/fisiologia , Condicionamento Físico Animal/métodos , Esforço Físico , Proteínas Tirosina Quinases/metabolismo
13.
Molecules ; 23(2)2018 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-29382106

RESUMO

Traditional Chinese medicine has been practiced for centuries in East Asia. Herbs are used to maintain health and cure disease. Certain Chinese herbs are known to protect and improve the brain, memory, and nervous system. To apply ancient knowledge to modern science, some major natural therapeutic compounds in herbs were extracted and evaluated in recent decades. Emerging studies have shown that herbal compounds have neuroprotective effects or can ameliorate neurodegenerative diseases. To understand the mechanisms of herbal compounds that protect against neurodegenerative diseases, we summarize studies that discovered neuroprotection by herbal compounds and compound-related mechanisms in neurodegenerative disease models. Those compounds discussed herein show neuroprotection through different mechanisms, such as cytokine regulation, autophagy, endoplasmic reticulum (ER) stress, glucose metabolism, and synaptic function. The interleukin (IL)-1ß and tumor necrosis factor (TNF)-α signaling pathways are inhibited by some compounds, thus attenuating the inflammatory response and protecting neurons from cell death. As to autophagy regulation, herbal compounds show opposite regulatory effects in different neurodegenerative models. Herbal compounds that inhibit ER stress prevent neuronal death in neurodegenerative diseases. Moreover, there are compounds that protect against neuronal death by affecting glucose metabolism and synaptic function. Since the progression of neurodegenerative diseases is complicated, and compound-related mechanisms for neuroprotection differ, therapeutic strategies may need to involve multiple compounds and consider the type and stage of neurodegenerative diseases.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Doenças Neurodegenerativas , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Morte Celular/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Neurônios/patologia
14.
J Biophotonics ; 11(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28464488

RESUMO

A developed temporal focusing-based multiphoton excitation microscope (TFMPEM) has a digital micromirror device (DMD) which is adopted not only as a blazed grating for light spatial dispersion but also for patterned illumination simultaneously. Herein, the TFMPEM has been extended to implement spatially modulated illumination at structured frequency and orientation to increase the beam coverage at the back-focal aperture of the objective lens. The axial excitation confinement (AEC) of TFMPEM can be condensed from 3.0 µm to 1.5 µm for a 50 % improvement. By using the TFMPEM with HiLo technique as two structured illuminations at the same spatial frequency but different orientation, reconstructed biotissue images according to the condensed AEC structured illumination are shown obviously superior in contrast and better scattering suppression. Picture: TPEF images of the eosin-stained mouse cerebellar cortex by conventional TFMPEM (left), and the TFMPEM with HiLo technique as 1.09 µm-1 spatially modulated illumination at 90° (center) and 0° (right) orientations.


Assuntos
Microscopia de Fluorescência por Excitação Multifotônica/métodos , Calibragem , Desenho de Equipamento , Microscopia de Fluorescência por Excitação Multifotônica/instrumentação
15.
Neurosci Lett ; 662: 142-146, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29051084

RESUMO

Metabolic disorders hamper the brain metabolism and functions. The astrocytic glucose-derived lactate is known to fill the increased energy needs of neurons during synaptic transmission. However, whether systemic metabolism dysregulation affects the astrocytic lactate metabolism in the brain remain unexamined. To address this question, we adopt a 12-week high-fat diet to induce metabolic disorders in adult mice, and the effects of high-fat diet on the lactate metabolism in the hippocampus were examined. Results showed that a 12-week high-fat diet induced obesity and insulin resistance in mice. High-fat diet also decreased the lactate content levels and the expression of glial glutamate transporters, GLAST and GLT-1, in the hippocampus. Strong correlations between the lactate levels and the levels of GLAST and GLT-1 were evidenced. In conclusion, high-fat feeding induces metabolic disorders and disrupts lactate metabolism in the hippocampus. GLAST and GLT-1 may contribute to the HFD-induced abnormalities of the hippocampal lactate metabolism.


Assuntos
Dieta Hiperlipídica , Transportador 1 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Hipocampo/metabolismo , Ácido Láctico/metabolismo , Animais , Modelos Animais de Doenças , Ácido Láctico/sangue , Masculino , Doenças Metabólicas/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/metabolismo
16.
Int J Mol Sci ; 18(6)2017 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28608819

RESUMO

Although many cardiovascular (CVD) medications, such as antithrombotics, statins, and antihypertensives, have been identified to treat atherosclerosis, at most, many of these therapeutic agents only delay its progression. A growing body of evidence suggests physical exercise could be implemented as a non-pharmacologic treatment due to its pro-metabolic, multisystemic, and anti-inflammatory benefits. Specifically, it has been discovered that certain anti-inflammatory peptides, metabolites, and RNA species (collectively termed "exerkines") are released in response to exercise that could facilitate these benefits and could serve as potential therapeutic targets for atherosclerosis. However, much of the relationship between exercise and these exerkines remains unanswered, and there are several challenges in the discovery and validation of these exerkines. This review primarily highlights major anti-inflammatory exerkines that could serve as potential therapeutic targets for atherosclerosis. To provide some context and comparison for the therapeutic potential of exerkines, the anti-inflammatory, multisystemic benefits of exercise, the basic mechanisms of atherosclerosis, and the limited efficacies of current anti-inflammatory therapeutics for atherosclerosis are briefly summarized. Finally, key challenges and future directions for exploiting these exerkines in the treatment of atherosclerosis are discussed.


Assuntos
Anti-Inflamatórios/uso terapêutico , Aterosclerose/terapia , Terapia por Exercício , Inflamação/terapia , Animais , Aterosclerose/complicações , Aterosclerose/imunologia , Aterosclerose/patologia , LDL-Colesterol/análise , LDL-Colesterol/imunologia , Terapia por Exercício/métodos , Humanos , Inflamação/complicações , Inflamação/imunologia , Inflamação/patologia
17.
Oncotarget ; 8(3): 4051-4061, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-27852055

RESUMO

The endoplasmic reticulum (ER) is a major site of cellular homeostasis regulation. Under the ER stress condition, Glioblastoma multiform (GBM) cells activate the unfolded protein response. In this study, we discovered isochaihulactone, a natural compound extracted from the Chinese traditional herb Nan-Chai-Hu, which can disrupt ER homeostasis in GBM cell lines. It can induce DNA damage inducible transcript 3 (DDIT3) expression which is independent of 78 kDa glucose-regulated protein (GRP78) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) expression. Flow cytometry results revealed that isochaihulactone trigger the cell cycle arrest at G2/M phase and apoptosis in GBM cells. Isochaihulactone induced DDIT3 led to the expression of NAG-1. The in vivo study showed that isochaihulactone suppressed tumor growth, and DDIT3 and Caspase3 overexpressed in the xenograft model, which is consistent with the in vitro study. Overall, the data revealed that isochaihulactone disrupted ER homeostasis in cancer cells by increasing DDIT3 and NAG-1 expression. Our finding also provides a therapeutic strategy by using isochaihulactone for GBM treatment.


Assuntos
4-Butirolactona/análogos & derivados , Antineoplásicos Fitogênicos/administração & dosagem , Benzodioxóis/administração & dosagem , Glioblastoma/tratamento farmacológico , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/metabolismo , 4-Butirolactona/administração & dosagem , 4-Butirolactona/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Benzodioxóis/farmacologia , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/metabolismo , Fator 15 de Diferenciação de Crescimento/metabolismo , Humanos , Camundongos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Biomed Opt Express ; 7(5): 1727-36, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27231617

RESUMO

Temporal focusing multiphoton microscopy (TFMPM) has the advantage of area excitation in an axial confinement of only a few microns; hence, it can offer fast three-dimensional (3D) multiphoton imaging. Herein, fast volumetric imaging via a developed digital micromirror device (DMD)-based TFMPM has been realized through the synchronization of an electron multiplying charge-coupled device (EMCCD) with a dynamic piezoelectric stage for axial scanning. The volumetric imaging rate can achieve 30 volumes per second according to the EMCCD frame rate of more than 400 frames per second, which allows for the 3D Brownian motion of one-micron fluorescent beads to be spatially observed. Furthermore, it is demonstrated that the dynamic HiLo structural multiphoton microscope can reject background noise by way of the fast volumetric imaging with high-speed DMD patterned illumination.

19.
Front Aging Neurosci ; 8: 57, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27047373

RESUMO

Age-related cognitive impairment has become one of the most common health threats in many countries. The biological substrate of cognition is the interconnection of neurons to form complex information processing networks. Experience-based alterations in the activities of these information processing networks lead to neuroadaptation, which is physically represented at the cellular level as synaptic plasticity. Although synaptic plasticity is known to be affected by aging, the underlying molecular mechanisms are not well described. Astrocytes, a glial cell type that is infrequently investigated in cognitive science, have emerged as energy suppliers which are necessary for meeting the abundant energy demand resulting from glutamatergic synaptic activity. Moreover, the concerted action of an astrocyte-neuron metabolic shuttle is essential for cognitive function; whereas, energetic incoordination between astrocytes and neurons may contribute to cognitive impairment. Whether altered function of the astrocyte-neuron metabolic shuttle links aging to reduced synaptic plasticity is unexplored. However, accumulated evidence documents significant beneficial effects of long-term, regular exercise on cognition and synaptic plasticity. Furthermore, exercise increases the effectiveness of astrocyte-neuron metabolic shuttle by upregulation of astrocytic lactate transporter levels. This review summarizes previous findings related to the neuronal activity-dependent astrocyte-neuron metabolic shuttle. Moreover, we discuss how aging and exercise may shape the astrocyte-neuron metabolic shuttle in cognition-associated brain areas.

20.
Sci Rep ; 6: 22864, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26960267

RESUMO

Microglial activation is implicated in the pathogenesis of Parkinson's disease (PD). Although the etiology of PD remains unclear, age and male gender are known PD risk factors. By comparing microglia and dopaminergic (DA) neurons in the substantia nigra (SN) of male and female mice of different ages, we found that the degrees of microglial activation and DA neuron loss increased with age in both genders, but were more pronounced in males, as were peripheral lipopolysaccharide (LPS)-induced microglial activation and DA neuron loss. A bilateral ovariectomy (OVX) eliminated the female-associated protection against age- and LPS-induced microglial activation, which suggests that ovary hormones are involved in gender-specific responses. Treating female mice with 17ß-estradiol supplements reduced the age-associated microglial activation in OVX mice. Moreover, pretreating mouse BV2 microglial cells with 17ß-estradiol inhibited LPS-induced elevation of Toll-like receptor 4, phosphorylated p38, and TNF-α levels. We then examined the effect of 17ß-estradiol on inward-rectifier K(+) channel Kir2.1, a known regulator of microglial activation. We found that 17ß-estradiol inhibited the Kir2.1 activity of BV2 cells by reducing the probability that the channel would be open. We conclude that age- and inflammation-associated microglial activation is attenuated by ovarian estrogen, because it inhibits Kir2.1.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Estradiol/farmacologia , Estrogênios/farmacologia , Microglia/efeitos dos fármacos , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Fatores Etários , Animais , Contagem de Células , Linhagem Celular , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Feminino , Lipopolissacarídeos/farmacologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Ovariectomia , Canais de Potássio Corretores do Fluxo de Internalização/antagonistas & inibidores , Fatores Sexuais , Substância Negra/citologia , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo
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