RESUMEN
Oxidative stress is one of the major culprits causing dopaminergic neuron loss in Parkinson's disease (PD). DJ-1 is a protein with multiple actions against oxidative stress, apoptosis, neuroinflammation, etc. DJ-1 expression is decreased in sporadic PD, therefore increasing DJ-1 expression might be beneficial in PD treatment. However, drugs known to upregulate DJ-1 are still lacking. In this study, we identified a novel DJ-1-elevating compound called ChemJ through luciferase assay-based high-throughput compound screening in SH-SY5Y cells and confirmed that ChemJ upregulated DJ-1 in SH-SY5Y cell line and primary cortical neurons. DJ-1 upregulation by ChemJ alleviated MPP+-induced oxidative stress. In exploring the underlying mechanisms, we found that the transcription factor CREB1 bound to DJ-1 promoter and positively regulated its expression under both unstressed and 1-methyl-4-phenylpyridinium-induced oxidative stress conditions and that ChemJ promoted DJ-1 expression via activating PKA/CREB1 pathway in SH-SY5Y cells. Our results demonstrated that ChemJ alleviated the MPP+-induced oxidative stress through a PKA/CREB1-mediated regulation of DJ-1 expression, thus offering a novel and promising avenue for PD treatment.
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Environmental factors, such as temperature and moisture, and plant factors, such as seed position on the mother plant, can affect seed viability and germination. However, little is known about the viability and germination of seeds in different positions on the mother plant after burial in soil under natural environmental conditions. Here, diaspores from three positions on a compound spike and seeds from two/three positions in a diaspore of the invasive diaspore-heteromorphic annual grass Aegilops tauschii were buried at four depths for more than 2 years (1-26 months) under natural conditions and viability and germination monitored monthly. Viability of seeds in each diaspore/seed position decreased as burial depth and duration increased and was associated with changes in soil temperature and moisture. Germination was highest at 2 cm and lowest at 10 cm soil depths, with peaks and valleys in autumn/spring and winter/summer, respectively. Overall, seeds in distal diaspore and distal seed positions had higher germination percentages than those in basal diaspore and basal seed positions, but basal ones lived longer than distal ones. Chemical content of fresh diaspores/seeds was related to diaspore/seed position effects on seed germination and viability during burial. We conclude that seeds in distal diaspores/seed positions have a 'high risk' strategy and those in basal positions a 'low risk' strategy. The two risk strategies may act as a bet-hedging strategy that spreads risks of germination failure in the soil seed bank over time, thereby facilitating the survival and invasiveness of A. tauschii.
Asunto(s)
Germinación , Poaceae , Semillas , Suelo , Germinación/fisiología , Semillas/fisiología , Semillas/crecimiento & desarrollo , Poaceae/fisiología , Poaceae/crecimiento & desarrollo , Suelo/química , Especies Introducidas , Temperatura , Estaciones del Año , AmbienteRESUMEN
Release from enemies can lead to rapid evolution in invasive plants, including reduced metabolic investment in defence. Conversely, reassociation with enemies leads to renewed evolution of defence, but the potential costs of this evolution are poorly documented. We report increased resistance of the invader Ambrosia artemisiifolia after reassociation with a coevolved specialist herbivore, and that this increase corresponds with reduced abiotic stress tolerance. Herbivore resistance was higher, but drought tolerance was lower in plants from populations with a longer reassociation history, and this corresponded with changes in phenylpropanoids involved in insect resistance and abiotic stress tolerance. These changes were corroborated by shifts in the expression of underlying biosynthetic genes and plant anti-oxidants. Together, our findings suggest rapid evolution of plant traits after reassociation with coevolved enemies, resulting in genetically based shifts in investment between abiotic and biotic stress responses, providing insights into co-evolution, plant invasion and biological control.
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Evolución Biológica , Herbivoria , Animales , Herbivoria/fisiología , Plantas , Insectos , Estrés FisiológicoRESUMEN
Non-native plants are typically released from specialist enemies but continue to be attacked by generalists, albeit at lower intensities. This reduced herbivory may lead to less investment in constitutive defences and greater investment in induced defences, potentially reducing defence costs. We compared herbivory on 27 non-native and 59 native species in the field and conducted bioassays and chemical analyses on 12 pairs of non-native and native congeners. Non-natives suffered less damage and had weaker constitutive defences, but stronger induced defences than natives. For non-natives, the strength of constitutive defences was correlated with the intensity of herbivory experienced, whereas induced defences showed the reverse. Investment in induced defences correlated positively with growth, suggesting a novel mechanism for the evolution of increased competitive ability. To our knowledge, these are the first linkages reported among trade-offs in plant defences related to the intensity of herbivory, allocation to constitutive versus induced defences, and growth.
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Herbivoria , Fenómenos Fisiológicos de las Plantas , PlantasRESUMEN
Mutations or triplication of the alpha synuclein (ASYN) gene contribute to synucleinopathies including Parkinson's disease (PD), Dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Recent evidence suggests that ASYN also plays an important role in amyloid-induced neurotoxicity, although the mechanism(s) remains unknown. One hypothesis is that accumulation of ASYN alters endolysosomal pathways to impact axonal trafficking and processing of the amyloid precursor protein (APP). To define an axonal function for ASYN, we used a transgenic mouse model of synucleinopathy that expresses a GFP-human ASYN (GFP-hASYN) transgene and an ASYN knockout (ASYN-/-) mouse model. Our results demonstrate that expression of GFP-hASYN in primary neurons derived from a transgenic mouse impaired axonal trafficking and processing of APP. In addition, axonal transport of BACE1, Rab5, Rab7, lysosomes and mitochondria were also reduced in these neurons. Interestingly, axonal transport of these organelles was also affected in ASYN-/- neurons, suggesting that ASYN plays an important role in maintaining normal axonal transport function. Therefore, selective impairment of trafficking and processing of APP by ASYN may act as a potential mechanism to induce pathological features of Alzheimer's disease (AD) in PD patients.
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Enfermedad de Parkinson , Sinucleinopatías , Humanos , Ratones , Animales , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Secretasas de la Proteína Precursora del Amiloide , Precursor de Proteína beta-Amiloide/genética , Ácido Aspártico Endopeptidasas , Enfermedad de Parkinson/genética , Ratones Transgénicos , Lisosomas/metabolismoRESUMEN
MAIN CONCLUSION: Differences in dispersal and dormancy of heteromorphic diaspores of Aegilos tauschii may increase its flexibility to invade/occupy weedy unpredictable habitats by spreading risk in space and time. In plant species that produce dimorphic seeds, there often is a negative relationship between dispersal and dormancy, with high dispersal-low dormancy in one morph and low dispersal-high dormancy in the other, which may function as a bet-hedging strategy that spreads the risk of survival and ensures reproductive success. However, the relationship between dispersal and dormancy and its ecological consequences in invasive annual grasses that produce heteromorphic diaspores is not well studied. We compared dispersal and dormancy responses of diaspores from the basal (proximal) to the distal position on compound spikes of Aegilops tauschii, an invasive grass with heteromorphic diaspores. Dispersal ability increased and degree of dormancy decreased as diaspore position on a spike increased from basal to distal. There was a significant positive correlation between length of awns and dispersal ability, and awn removal significantly promoted seed germination. Germination was positively correlated with GA concentration and negatively correlated with ABA concentration, and the ABA: GA ratio was high in seeds with low germination/high dormancy. Thus, there was a continuous inverse-linear relationship between diaspore dispersal ability and degree of dormancy. This negative relationship between diaspore dispersal and degree of dormancy at different positions on a spike of Aegilops tauschii may facilitate seedling survival in space and time.
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Aegilops , Dispersión de Semillas , Poaceae , Dispersión de Semillas/fisiología , Germinación/fisiología , Plantones , Semillas/fisiología , Latencia en las PlantasRESUMEN
BACKGROUND AND PURPOSE: Bilateral deep brain stimulation (DBS) surgery targeting the globus pallidus internus (GPi) or the subthalamic nucleus (STN) is widely used in medication-refractory dystonia. However, evidence regarding target selection considering various symptoms remains limited. This study aimed to compare the effectiveness of these two targets in patients with isolated dystonia. METHODS: This retrospective study evaluated 71 consecutive patients (GPi-DBS group, n = 32; STN-DBS group, n = 39) with isolated dystonia. Burke-Fahn-Marsden Dystonia Rating Scale scores and quality of life were evaluated preoperatively and at 1, 6, 12, and 36 months postoperatively. Cognition and mental status were assessed preoperatively and at 36 months postoperatively. RESULTS: Targeting the STN (STN-DBS) yielded effects within 1 month (65% vs. 44%; p = 0.0076) and was superior at 1 year (70% vs. 51%; p = 0.0112) and 3 years (74% vs. 59%; p = 0.0138). For individual symptoms, STN-DBS was preferable for eye involvement (81% vs. 56%; p = 0.0255), whereas targeting the GPi (GPi-DBS) was better for axis symptoms, especially for the trunk (82% vs. 94%; p = 0.015). STN-DBS was also favorable for generalized dystonia at 36-month follow-up (p = 0.04) and required less electrical energy (p < 0.0001). Disability, quality of life, and depression and anxiety measures were also improved. Neither target influenced cognition. CONCLUSIONS: We demonstrated that the GPi and STN are safe and effective targets for isolated dystonia. The STN has the benefits of fast action and low battery consumption, and is superior for ocular dystonia and generalized dystonia, while the GPi is better for trunk involvement. These findings may offer guidance for future DBS target selection for different types of dystonia.
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Estimulación Encefálica Profunda , Distonía , Trastornos Distónicos , Núcleo Subtalámico , Humanos , Globo Pálido , Distonía/terapia , Estudios de Seguimiento , Calidad de Vida , Estudios Retrospectivos , Resultado del Tratamiento , Trastornos Distónicos/terapiaRESUMEN
Parkinson's disease (PD) is a common neurodegenerative motor disorder characterized by a dramatic reduction in pars compacta of substantia nigra dopaminergic neurons and striatal dopamine (DA) levels. Mutations or deletions in the PARK7/DJ-1 gene are associated with an early-onset familial form of PD. DJ-1 protein prevents neurodegeneration via its regulation of oxidative stress and mitochondrial function as well as its roles in transcription and signal transduction. In this study, we investigated how loss of DJ-1 function affected DA degradation, ROS generation and mitochondrial dysfunction in neuronal cells. We showed that loss of DJ-1 significantly increased the expression of monoamine oxidase (MAO)-B but not MAO-A in both neuronal cells and primary astrocytes. In DJ-1-knockout (KO) mice, MAO-B protein levels in the substantia nigra (SN) and striatal regions were significantly increased. We demonstrated that the induction of MAO-B expression by DJ-1 deficiency depended on early growth response 1 (EGR1) in N2a cells. By coimmunoprecipitation omics analysis, we found that DJ-1 interacted with receptor of activated protein C kinase 1 (RACK1), a scaffolding protein, and thus inhibited the activity of the PKC/JNK/AP-1/EGR1 cascade. The PKC inhibitor sotrastaurin or the JNK inhibitor SP600125 completely inhibited DJ-1 deficiency-induced EGR1 and MAO-B expression in N2a cells. Moreover, the MAO-B inhibitor rasagiline inhibited mitochondrial ROS generation and rescued neuronal cell death caused by DJ-1 deficiency, especially in response to MPTP stimulation in vitro and in vivo. These results suggest that DJ-1 exerts neuroprotective effects by inhibiting the expression of MAO-B distributed at the mitochondrial outer membrane, which mediates DA degradation, ROS generation and mitochondrial dysfunction. This study reveals a mechanistic link between DJ-1 and MAO-B expression and contributes to understanding the crosslinks among pathogenic factors, mitochondrial dysfunction and oxidative stress in PD pathogenesis.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Ratones , Animales , Enfermedad de Parkinson/metabolismo , Monoaminooxidasa/genética , Monoaminooxidasa/metabolismo , Monoaminooxidasa/farmacología , Regulación hacia Arriba , Especies Reactivas de Oxígeno/metabolismo , Neuronas Dopaminérgicas/metabolismo , Transducción de Señal , Enfermedades Neurodegenerativas/metabolismo , Receptores de Cinasa C Activada/genética , Receptores de Cinasa C Activada/metabolismo , Receptores de Cinasa C Activada/farmacología , Proteína Desglicasa DJ-1/genética , Proteína Desglicasa DJ-1/metabolismoRESUMEN
Invasive plants can change soil properties resulting in improved growth. Although invaders are known to alter soil chemistry, it remains unclear if chemicals secreted by roots facilitate invasive plant-soil mutualisms. With up to 19 confamilial pairs of invasive and native plants, and most of which were congeners, we explored the root exudate-induced changes in plant-arbuscular mycorrhizal (AM) fungal mutualisms. We found that, relative to natives, invaders had greater AM colonization, greater biomass and their root exudates contained higher concentrations of two common chemical signals - quercetin and strigolactones - which are known to stimulate AM fungal growth and root colonization. An exudate exchange experiment showed that root exudates from invaders increased AM colonization more than exudates from natives. However, application of activated carbon led to greater reduction in AM colonization and plant biomass for invaders than natives, suggesting stronger effects of chemical signals in root exudates from invaders. We show that nonnative plants promote interactions with soil mutualists via enhancing root exudate chemicals, which could have important implications for invasion success.
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Micorrizas , Suelo , Carbón Orgánico/farmacología , Exudados y Transudados , Raíces de Plantas/microbiología , Plantas , Quercetina/farmacología , Suelo/química , Microbiología del SueloRESUMEN
Increasing evidence has pointed to that dysregulation of the endo-lysosomal system is an early cellular phenotype of pathogenesis for Alzheimer's disease (AD). Rab5, a small GTPase, plays a critical role in mediating these processes. Abnormal overactivation of Rab5 has been observed in post-mortem brain samples of Alzheimer's patients as well as brain samples of mouse models of AD. Recent genome-wide association studies of AD have identified RIN3 (Ras and Rab interactor 3) as a novel risk factor for the disease. RIN3 that functions as a guanine nucleotide exchange factor for Rab5 may serve as an important activator for Rab5 in AD pathogenesis. In this review, we present recent research highlights on the possible roles of dysregulation of Rab5-mediated endocytic pathways in contributing to early pathogenesis of AD.
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Enfermedad de Alzheimer/metabolismo , Transporte Axonal/fisiología , Endosomas/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Proteínas de Unión al GTP rab5/metabolismo , Animales , Estudio de Asociación del Genoma Completo , HumanosRESUMEN
Lack of dopamine production and neurodegeneration of dopaminergic neurons in the substantia nigra are considered as the major characteristics of Parkinson's disease, a prevalent movement disorder worldwide. DJ-1 mutation leading to loss of its protein functions is a genetic factor of PD. In this study, our results illustrated that DJ-1 can directly interact with Ca2+ /calmodulin-dependent protein kinase kinase ß (CaMKKß) and modifies the cAMP-responsive element binding protein 1 (CREB1) activity, thus regulates tyrosine hydroxylase (TH) expression. In Dj-1 knockout mouse substantia nigra, the levels of TH and the phosphorylation of CREB1 Ser133 are significantly decreased. Moreover, Dj-1 deficiency suppresses the phosphorylation of CaMKIV (Thr196/200) and CREB1 (Ser133), subsequently inhibits TH expression in vitro. Furthermore, Knockdown of Creb1 abolishes the effects of DJ-1 on TH regulation. Our data reveal a novel pathway in which DJ-1 regulates CaMKKß/CaMKIV/CREB1 activities to facilitate TH expression.
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Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/metabolismo , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Enfermedad de Parkinson/patología , Proteína Desglicasa DJ-1/metabolismo , Tirosina 3-Monooxigenasa/biosíntesis , Animales , Línea Celular Tumoral , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Células HEK293 , Células HeLa , Humanos , Ratones , Ratones Noqueados , Fosforilación , Transducción de Señal , Sustancia Negra/patología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
BACKGROUND AND AIMS: The strengths of biotic interactions such as herbivory are expected to decrease with increasing latitude for native species. To what extent this applies to invasive species and what the consequences of this variation are for competition among native and invasive species remain unexplored. Here, herbivore impacts on the invasive plant Alternanthera philoxeroides and its competition with the native congener A. sessilis were estimated across latitudes in China. METHODS: An common garden experiment spanning ten latitudinal degrees was conducted to test how herbivore impacts on A. philoxeroides and A. sessilis, and competition between them change with latitude. In addition, a field survey was conducted from 21°N to 36.8°N to test whether A. philoxeroides invasiveness changes with latitude in nature as a result of variations in herbivory. KEY RESULTS: In the experiment, A. sessilis cover was significantly higher than A. philoxeroides cover when they competed in the absence of herbivores, but otherwise their cover was comparable at low latitude. However, A. philoxeroides cover was always higher on average than A. sessilis cover at middle latitude. At high latitude, only A. sessilis emerged in the second year. Herbivore abundance decreased with latitude and A. philoxeroides emerged earlier than A. sessilis at middle latitude. In the field survey, the ratio of A. philoxeroides to A. sessilis cover was hump shaped with latitude. CONCLUSION: These results indicate that herbivory may promote A. philoxeroides invasion only at low latitude by altering the outcome of competition in favour of the invader and point to the importance of other factors, such as earlier emergence, in A. philoxeroides invasion at higher latitudes. These results suggest that the key factors promoting plant invasions might change with latitude, highlighting the importance of teasing apart the roles of multiple factors in plant invasions within a biogeographic framework.
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Amaranthaceae , Herbivoria , China , Especies Introducidas , PlantasRESUMEN
BACKGROUND: Microglia in the central nervous system (CNS) were reported to play crucial role in neurodegeneration. Previous studies showed that P2Y6 receptor (P2Y6R) mainly contributed to microglia activation and phagocytosis in CNS. However, the level of P2Y6R in Parkinson's disease (PD) patients is unclear. Therefore, we measured the level of P2Y6R in PD patients and speculated whether it could be a potential biomarker for PD. Given on the basis that P2Y6R was higher in PD patients, we further explored the mechanisms underlying P2Y6R in the pathogenesis of PD. METHODS: We tested the expression level of P2Y6R in the peripheral blood mononuclear cells (PBMCs) among 145 PD patients, 170 healthy controls, and 30 multiple system atrophy (MSA) patients. We also used a lipopolysaccharide (LPS)-stimulated microglial cell culture model to investigate (i) the effects of LPS on P2Y6R expression with western blot and RT-PCR, (ii) the effects of LPS on UDP expression using HPLC, (iii) the effects of UDP/P2Y6R signaling on cytokine expression using western blot, RT-PCR, and ELISA, and (iv) the signaling pathways activated by the P2Y6R involved in the neuroinflammation. RESULTS: Expression levels of P2Y6R in PD patients were higher than healthy controls and MSA patients. P2Y6R could be a good biomarker of PD. P2Y6R was also upregulated in LPS-treated BV-2 cells and involved in proinflammatory cytokine release through an autocrine loop based on LPS-triggered UDP secretion and accelerated neuroinflammatory responses through the ERK1/2 pathway. Importantly, blocking UDP/P2Y6R signaling could reverse these pathological processes. CONCLUSIONS: P2Y6R may be a potential clinical biomarker of PD. Blocking P2Y6R may be a potential therapeutic approach to the treatment of PD patients through inhibition of microglia-activated neuroinflammation.
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Leucocitos Mononucleares/metabolismo , Microglía/metabolismo , Atrofia de Múltiples Sistemas/metabolismo , Enfermedad de Parkinson/metabolismo , Receptores Purinérgicos P2/biosíntesis , Anciano , Anciano de 80 o más Años , Animales , Línea Celular Tumoral , Femenino , Humanos , Inflamación/metabolismo , Inflamación/patología , Leucocitos Mononucleares/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Atrofia de Múltiples Sistemas/patología , Enfermedad de Parkinson/patologíaRESUMEN
Climate warming may affect biological invasions by altering competition between native and non-native species, but these effects may depend on biotic interactions. In field surveys at 33 sites in China along a latitudinal and temperature gradient from 21°N to 30.5°N and a 2-yr field experiment at 30.5°N, we tested the role of the biocontrol beetle Agasicles hygrophila in mediating warming effects on competition between the invasive plant Alternanthera philoxeroides and the native plant Alternanthera sessilis. In surveys, native populations were perennial below 25.8°N but only annual populations were found above 26.5°N where the invader dominated the community. Beetles were present throughout the gradient. Experimental warming (+ 1.8°C) increased native plant performance directly by shifting its lifecycle from annual to perennial, and indirectly by releasing the native from competition via disproportionate increases in herbivory on the invader. Consequently, warming shifted the plant community from invader-dominated to native-dominated but only in the presence of the beetle. Our results show that herbivores can play a critical role in determining warming effects on plant communities and species invasions. Understanding how biotic interactions shape responses of communities to climate change is crucial for predicting the risk of plant invasions.
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Amaranthaceae/fisiología , Cambio Climático , Escarabajos/fisiología , Especies Introducidas , Control Biológico de Vectores , Animales , Biomasa , Germinación , Modelos Biológicos , Tallos de la Planta/anatomía & histología , Análisis de Regresión , Plantones/fisiología , Semillas/fisiología , Especificidad de la EspecieRESUMEN
Spatially separated aboveground (AG) and belowground (BG) herbivores are closely linked through shared host plants, and both patterns of AG-BG interactions and plant responses may vary among plant genotypes. We subjected invasive (USA) and native (China) genotypes of tallow tree (Triadica sebifera) to herbivory by the AG specialist leaf-rolling weevil Heterapoderopsis bicallosicollis and/or the root-feeding larvae of flea beetle Bikasha collaris. We measured leaf damage and leaves rolled by weevils, quantified beetle survival, and analyzed flavonoid and tannin concentrations in leaves and roots. AG and BG herbivores formed negative feedbacks on both native and invasive genotypes. Leaf damage by weevils and the number of beetle larvae emerging as adults were higher on invasive genotypes. Beetles reduced weevil damage and weevils reduced beetle larval emergence more strongly for invasive genotypes. Invasive genotypes had lower leaf and root tannins than native genotypes. BG beetles decreased leaf tannins of native genotypes but increased root tannins of invasive genotypes. AG herbivory increased root flavonoids of invasive genotypes while BG herbivory decreased leaf flavonoids. Invasive genotypes had lower AG and BG herbivore resistance, and negative AG-BG herbivore feedbacks were much stronger for invasive genotypes. Lower tannin concentrations explained overall better AG and BG herbivore performances on invasive genotypes. However, changes in tannins and flavonoids affected AG and BG herbivores differently. These results suggest that divergent selection on chemical production in invasive plants may be critical in regulating herbivore performances and novel AG and BG herbivore communities in new environments.
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Escarabajos , Herbivoria , Animales , Euphorbiaceae , Genotipo , Hojas de la Planta , Raíces de Plantas , PlantasRESUMEN
BACKGROUND As the second most common neurodegenerative disorder after Alzheimer's disease (AD), Parkinson's disease (PD) principally impacts the motor system in approximately 7 million patients worldwide. The present study aimed to explore the effects of cluster of differentiation (CD200) on adenosine triphosphate-sensitive potassium (KATP) channels and inflammatory response in PD mice. MATERIAL AND METHODS We created an in vivo PD model by intraperitoneal injection of 30 mg/kg/day 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP. HCL) for 5 consecutive days, and we created an in vitro PD model by injection of 100 µM 1-methyl-4-phenylpyridinium ion (MPP+) in primary microglia cells. Expression level of CD200/CD200R, inwardly rectifying potassium (Kir6.1/6.2), and sulfonylurea receptor (Sur1/2) were detected by Western blot (WB). Immunohistochemistry (IHC) was utilized to assess CD11b (microglia marker) and tyrosine hydroxylase (TH, a marker reveals dopamine level in neurons) expression levels. An in vitro PD model was applied to detect the influence of CD200 on ATP and inflammatory factors released from microglia. Interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß mRNA levels were explored by realtime quantitative polymerase chain reaction (RT-QPCR), and their protein levels were identified by enzyme-linked immunosorbent assay (ELISA). RESULTS WB exhibited time-dependent down-regulation of CD200/CD200R in cerebra of PD mice compared to control mice, with Kir 6.1 and SUR 2 expressed mainly in microglia. IHC showed that CD11b reached a peak at the 1st day after MPTP treatment, followed by time-dependent reduction, and TH decreased noticeably after MPTP induction. RT-QPCR demonstrated that compared with controls, IFN-γ, TNF-α, and IL-1ß mRNA levels were significantly elevated at MPTP-1d, was reduced at MPTP-3d, and then returned to baseline at MPTP-7d. IHC showed that MPP+ significantly elevated microglia release of ATP. Similar to the effect of pinacidil (K+ channel opener), CD200 remarkably depressed MPP+-induced ATP release. ELISA showed that MPP+ significantly increased IFN-γ, TNF-α, and IL-1ß release, and CD200 and pinacidil remarkably suppressed this elevation. CONCLUSIONS Our results show a novel role of CD200 in promoting opening of the KATP channel, inhibiting microglia activation and release of ATP, as well as inflammatory factors, thus protecting dopaminergic (DA) neurons against damage and alleviating PD.
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Antígenos CD/metabolismo , Canales KATP/metabolismo , Microglía/metabolismo , Enfermedad de Parkinson/metabolismo , Animales , Modelos Animales de Enfermedad , Dopamina , Regulación hacia Abajo , Interleucina-1beta/metabolismo , Ratones , Ratones Endogámicos C57BL , Microglía/patología , Neuronas/metabolismo , Neuronas/patología , Fármacos Neuroprotectores/metabolismo , Enfermedad de Parkinson/patología , Cultivo Primario de Células , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Climate change may shift interactions of invasive plants, herbivorous insects and native plants, potentially affecting biological control efficacy and non-target effects on native species. Here, we show how climate warming affects impacts of a multivoltine introduced biocontrol beetle on the non-target native plant Alternanthera sessilis in China. In field surveys across a latitudinal gradient covering their full distributions, we found beetle damage on A. sessilis increased with rising temperature and plant life history changed from annual to perennial. Experiments showed that elevated temperature changed plant life history and increased insect overwintering, damage and impacts on seedling recruitment. These results suggest that warming can shift phenologies, increase non-target effect magnitude and increase non-target effect occurrence by beetle range expansion to additional areas where A. sessilis occurs. This study highlights the importance of understanding how climate change affects species interactions for future biological control of invasive species and conservation of native species.
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Amaranthaceae , Agentes de Control Biológico , Cambio Climático , Escarabajos , Herbivoria , Animales , China , Ecosistema , Especies IntroducidasRESUMEN
BACKGROUND AND AIMS: Many plants produce extrafloral nectar (EFN), and increase production following above-ground herbivory, presumably to attract natural enemies of the herbivores. Below-ground herbivores, alone or in combination with those above ground, may also alter EFN production depending on the specificity of this defence response and the interactions among herbivores mediated through plant defences. To date, however, a lack of manipulative experiments investigating EFN production induced by above- and below-ground herbivory has limited our understanding of how below-ground herbivory mediates indirect plant defences to affect above-ground herbivores and their natural enemies. METHODS: In a greenhouse experiment, seedlings of tallow tree (Triadica sebifera) were subjected to herbivory by a specialist flea beetle (Bikasha collaris) that naturally co-occurs as foliage-feeding adults and root-feeding larvae. Seedlings were subjected to above-ground adults and/or below-ground larvae herbivory, and EFN production was monitored. KEY RESULTS: Above- and/or below-ground herbivory significantly increased the percentage of leaves with active nectaries, the volume of EFN and the mass of soluble solids within the nectar. Simultaneous above- and below-ground herbivory induced a higher volume of EFN and mass of soluble solids than below-ground herbivory alone, but highest EFN production was induced by above-ground herbivory when below-ground herbivores were absent. CONCLUSIONS: The induction of EFN production by below-ground damage suggests that systemic induction underlies some of the EFN response. The strong induction by above-ground herbivory in the absence of below-ground herbivory points to specific induction based on above- and below-ground signals that may be adaptive for this above-ground indirect defence.
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Escarabajos/fisiología , Euphorbiaceae/química , Néctar de las Plantas/metabolismo , Animales , Euphorbiaceae/fisiología , Herbivoria , Interacciones Huésped-Parásitos , Larva , Hojas de la Planta/química , Hojas de la Planta/fisiología , Raíces de Plantas/química , Raíces de Plantas/fisiología , Brotes de la Planta/química , Brotes de la Planta/fisiologíaRESUMEN
PD (Parkinson's disease) is a complex disorder that is associated with neuronal loss or dysfunction caused by genetic risks, environmental factors and advanced aging. It has been reported that DJ-1 mutations rendered neurons sensitive to oxidative damage, which led to the onset of familiar PD. However, the molecular mechanism is still unclear. In the present study we show that DJ-1 interacts with RACK1 (receptor of activated C kinase 1) and increases its dimerization and protein stability. The DJ-1 transgene protects cortical neurons from H2O2-induced apoptosis, and this protective effect is abrogated by knocking down RACK1. Similarly, deletion of DJ-1 in cortical neurons increases the sensitivity to H2O2, and the damage can be significantly rescued by DJ-1 or DJ-1/RACK1 co-transfection, but not by RACK1 alone. We observed further that the interaction of DJ-1 and RACK1 is disrupted by H2O2 or MPP+ (1-methyl-4-phenylpyridinium) treatment, and the protein levels of DJ-1 and RACK1 decreased in neurodegenerative disease models. Taken together, the DJ-1-RACK1 complex protects neurons from oxidative stress-induced apoptosis, with the implication that DJ-1 and RACK1 might be novel targets in the treatment of neurodegenerative diseases.