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Most ferns occur in moist and shaded environments; their relatively narrow band of survival conditions increase their extinction risk under Anthropocene-linked climate change. Osmundastrum cinnamomeum (L.) C. Presl is a perennial fern that has a natural distribution primarily encompassing the East Asian mountains. In this study, we characterized the vegetation and environmental factors in low- and high-elevation mountain ranges and montane wetlands to elucidate the optimal habitat for O. cinnamomeum. We found that populations of O. cinnamomeum developed better in high-elevation mountains than in low-elevation mountains. However, the low light intensity in high mountain forests reduces opportunities for reproduction. The montane wetlands recorded the highest biomass among the three habitat types, and the investment in reproduction was also significantly higher. The montane wetlands also showed higher light intensity, substrate fertility, and water content. Overall, the montane wetlands were found to be the optimal habitat for O. cinnamomeum. At lower elevations, lower precipitation, higher temperatures, human disturbance, and low substrate water could be factors limiting the expansion of this fern's distribution. Our study points to the importance of conserving montane wetlands to prevent the extinction of ferns.
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This study explores how elevated carbon dioxide (CO2) levels affects the growth and defense mechanisms of plants. We focused on Aristolochia contorta Bunge (Aristolochiaceae), a wild plant that exhibits growth reduction under elevated CO2 in the previous study. The plant has Sericinus montela Gray (Papilionidae) as a specialist herbivore. By analyzing primary metabolites, understanding both the growth and defense response of plants to herbivory under elevated CO2 conditions is possible. The experiment was conducted across four groups, combining two CO2 concentration conditions (ambient CO2 and elevated CO2) with two herbivory conditions (herbivory treated and untreated). Although many plants exhibit increased growth under elevated CO2 levels, A. contorta exhibited reduced growth with lower height, dry weight, and total leaf area. Under herbivory, A. contorta triggered both localized and systemic responses. More primary metabolites exhibited significant differences due to herbivory treatment in systemic tissue than local leaves that herbivory was directly treated. Herbivory under elevated CO2 level triggered more significant responses in primary metabolites (17 metabolites) than herbivory under ambient CO2 conditions (five metabolites). Several defense-related metabolites exhibited higher concentrations in the roots and lower concentrations in the leaves in response to the herbivory treatment in the elevated CO2 group. This suggests a potential intensification of defensive responses in the underground parts of the plant under elevated CO2 levels. Our findings underscore the importance of considering both abiotic and biotic factors in understanding plant responses to environmental changes. The adaptive strategies of A. contorta suggest a complex response mechanism to elevated CO2 and herbivory pressures.
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17ß-Estradiol is an ovarian hormone that regulates energy circulation and storage by acting on the central nervous system. However, the metabolic differences between the blood and brain when stimulated by 17ß-estradiol are poorly understood. Moreover, research using menopause-induced models to investigate primary metabolites in the blood and brain is limited. Thus, this study aimed to identify metabolic changes in the plasma and brain resulting from 17ß-estradiol supplementation in an estrogen-deficient mouse model. Three groups of mice were utilized: sham-operated mice (Sham), ovariectomized mice (OVX), and ovariectomized mice that received a weekly supplementation of 17ß-estradiol (E2). Plasma and brain samples from these mice were subjected to metabolic analysis using gas chromatography-time-of-flight-mass spectrometry. Compared with the plasma samples from the Sham and OVX groups, the plasma samples from the E2 group contained higher contents of branched-chain amino acids (BCAAs), such as valine, isoleucine, and leucine. Meanwhile, the brain samples from the E2 group contained higher contents of most metabolites, including BCAAs, neurotransmitters, tricarboxylic acid cycle intermediates, and fatty acids, than those from the two other groups. This study is the first to reveal differences in energy metabolism induced by 17ß-estradiol supplementation through brain metabolic profiling of ovariectomized mice, emphasizing the importance of brain metabolic profiling in menopausal hormone research.
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The phenology has gained considerably more attention in recent times of climate change. The transition from vegetative to reproductive phases is a critical process in the life history of plants, closely tied to phenology. In an era of climate change, understanding how environmental factors affect this transition is of paramount importance. This study consisted of field surveys and a greenhouse experiment on the reproductive biology of Northern pipevine (Aristolochia contorta Bunge). During field surveys, we investigated the environmental factors and growth characteristics of mature A. contorta, with a focus on both its vegetative and reproductive phases. In its successful flowering during the reproductive phase, A. contorta grew under the conditions of 40% relative light intensity and 24% soil moisture content, and had a vertical rhizome. In the greenhouse experiments, we examined the impact of increased CO2 concentration on the growth and development of 10-year-old A. contorta, considering the effect of rhizome direction. Planted with a vertical rhizome direction, A. contorta exhibited sufficient growth for flowering under ambient CO2 concentrations. In contrast, when planted with a horizontal rhizome direction, it was noted to significantly impede successful growth and flowering under elevated CO2 concentrations. This hindered the process of flowering, highlighting the pivotal role of substantial vegetative growth in achieving successful flowering. Furthermore, we observed a higher number of underground buds and shoots under the conditions of elevated CO2 concentration and a horizontal rhizome direction instead of flowering. Elevated CO2 concentrations also exhibited diverse effects on mature A. contorta's flower traits, resulting in smaller flower size, shorter longevity, and reduced stigma receptivity, and pollen viability. The study shed light on elevated CO2 concentrations can hinder growth, potentially obstructing sexual reproduction and diminishing genetic diversity.
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BACKGRUOUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors. METHODS: Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice. RESULTS: Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus. CONCLUSION: This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment.
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Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Camundongos , Animais , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Hipotálamo/metabolismo , Glucose/metabolismo , Fenótipo , Neurônios/metabolismo , Sódio/metabolismoRESUMO
Insects are vital pollinators for angiosperms, playing a crucial role in their reproductive success and fruit production. Aristolochia contorta is a perennial herbaceous vine that occurs in fragmented populations across East Asia. One notable feature of this plant is its trap flower, which employs a unique mechanism to attract, trap, retain, and release insects, ensuring effective pollination. The presence of this trap flower significantly influences the pollination system of A. contorta. Field surveys and pollination experiments were conducted to understand the processes and effectiveness of its pollination mechanism. It was allogamous and was pollinated by the species from Ceratopogonidae. During the insect attraction stage, 11.57% of the flowers contained insects, primarily Ceratopogonidae spp. Most Ceratopogonidae spp. concentrated in few flowers, indicating that although overall attraction might be modest, specific flowers acted as significant focal points for gathering. Trichomes effectively trapped Ceratopogonidae spp. inside flower tubes. In the retention stage, 26.16% of Ceratopogonidae spp. were loaded with pollen grains, but only 7.91% of those exited the flowers in the release stage. The sticky texture of the perianth's internal cavity posed challenges during this release, leading to adhesion and clogging of the narrow perianth tube. Consequently, a significant portion of Ceratopogonidae spp. became trapped on the perianth wall and perished. This highlights that despite the significant energy and resources invested in flower development, the perianth contributes to the low pollination effectiveness. This study revealed additive factors with negative effects on pollination, including the densely clustered distribution of its pollinators within only a few flowers, insufficient pollen loading onto pollinators, hindered release of entrapped pollinators due to the perianth adhesive surface, and a high rate of defective pollen grains in A. contorta. These factors account for the observed phenomenon of low fruit set (7.7%) and contribute to the diminished rate of sexual reproduction in A. contorta populations. This might lead the species to heavily rely on asexual reproduction, which could potentially lead to gene erosion within populations. The implications of these findings extend to the ecological and conservation aspects, emphasizing the need to understand and conserve the unique pollination system of A. contorta.
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Cisplatin is a chemotherapeutic drug commonly used for treating different types of cancer. However, long-term use can lead to side effects, including anorexia, nausea, vomiting, and weight loss, which negatively affect the patient's quality of life and ability to undergo chemotherapy. This study aimed to investigate the mechanisms underlying the development of a negative energy balance during cisplatin treatment. Mice treated with cisplatin exhibit reduced food intake, body weight, and energy expenditure. We observed altered neuronal activity in the hypothalamic nuclei involved in the regulation of energy metabolism in cisplatin-treated mice. In addition, we observed activation of microglia and inflammation in the hypothalamus following treatment with cisplatin. Consistent with this finding, inhibition of microglial activation effectively rescued cisplatin-induced anorexia and body weight loss. The present study identified the role of hypothalamic neurons and inflammation linked to microglial activation in the anorexia and body weight loss observed during cisplatin treatment. These findings provide insight into the mechanisms underlying the development of metabolic abnormalities during cisplatin treatment and suggest new strategies for managing these side effects.
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TTF-1 stimulates appetite by regulating the expression of agouti-related peptide (AgRP) and proopiomelanocortin (POMC) genes in the hypothalamus of starving animals. However, the mechanism underlying TTF-1's response to decreased energy levels remains elusive. Here, we provide evidence that the NAD+-dependent deacetylase, sirtuin1 (Sirt1), activates TTF-1 in response to energy deficiency. Energy deficiency leads to a twofold increase in the expression of both Sirt1 and TTF-1, leading to the deacetylation of TTF-1 through the interaction between the two proteins. The activation of Sirt1, induced by energy deficiency or resveratrol treatment, leads to a significant increase in the deacetylation of TTF-1 and promotes its nuclear translocation. Conversely, the inhibition of Sirt1 prevents these Sirt1 effects. Notably, a point mutation in a lysine residue of TTF-1 significantly disrupts its deacetylation and thus nearly completely hinders its ability to regulate AgRP and POMC gene expression. These findings highlight the importance of energy-deficiency-induced deacetylation of TTF-1 in the control of AgRP and POMC gene expression.
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Pró-Opiomelanocortina , Sirtuína 1 , Animais , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína Relacionada com Agouti/genética , Proteína Relacionada com Agouti/metabolismo , Hipotálamo/metabolismoRESUMO
Eukaryotic translation initiation factor 2α (eIF2α) is a key mediator of the endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR). In mammals, eIF2α is phosphorylated by overnutrition-induced ER stress and is related to the development of obesity. Here, we studied the function of phosphorylated eIF2α (p-eIF2α) in agouti-related peptide (AgRP) neurons using a mouse model (AgRPeIF2αA/A) with an AgRP neuron-specific substitution from Ser 51 to Ala in eIF2α, which impairs eIF2α phosphorylation in AgRP neurons. These AgRPeIF2αA/A mice had decreases in starvation-induced AgRP neuronal activity and food intake and an increased responsiveness to leptin. Intriguingly, impairment of eIF2α phosphorylation produced decreases in the starvation-induced expression of UPR and autophagy genes in AgRP neurons. Collectively, these findings suggest that eIF2α phosphorylation regulates AgRP neuronal activity by affecting intracellular responses such as the UPR and autophagy during starvation, thereby participating in the homeostatic control of whole-body energy metabolism. ARTICLE HIGHLIGHTS: This study examines the impact of eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, triggered by an energy deficit, on hypothalamic AgRP neurons and its subsequent influence on whole-body energy homeostasis. Impaired eIF2α phosphorylation diminishes the unfolded protein response and autophagy, both of which are crucial for energy deficit-induced activation of AgRP neurons. This study highlights the significance of eIF2α phosphorylation as a cellular marker indicating the availability of energy in AgRP neurons and as a molecular switch that regulates homeostatic feeding behavior.
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Fator de Iniciação 2 em Eucariotos , eIF-2 Quinase , Animais , Proteína Relacionada com Agouti/genética , Proteína Relacionada com Agouti/metabolismo , eIF-2 Quinase/metabolismo , Estresse do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/metabolismo , Comportamento Alimentar , Mamíferos/metabolismo , Neurônios/metabolismo , Peptídeos/metabolismo , Fosforilação , CamundongosRESUMO
Plants need to balance investments in growth and defense throughout their life to increase their fitness. To optimize fitness, levels of defense against herbivores in perennial plants may vary according to plant age and season. However, secondary plant metabolites often have a detrimental effect on generalist herbivores, while many specialists have developed resistance to them. Therefore, varying levels of defensive secondary metabolites depending on plant age and season may have different effects on the performance of specialist and generalist herbivores colonizing the same host plants. In this study, we analyzed concentrations of defensive secondary metabolites (aristolochic acids) and the nutritional value (C/N ratios) of 1st-, 2nd- and 3rd-year Aristolochia contorta in July (the middle of growing season) and September (the end of growing season). We further assessed their effects on the performances of the specialist herbivore Sericinus montela (Lepidoptera: Papilionidae) and the generalist herbivore Spodoptera exigua (Lepidoptera: Noctuidae). Leaves of 1st-year A. contorta contained significantly higher concentrations of aristolochic acids than those of older plants, with concentrations tending to decrease over the first-year season. Therefore, when first year leaves were fed in July, all larvae of S. exigua died and S. montela showed the lowest growth rate compared to older leaves fed in July. However, the nutritional quality of A. contorta leaves was lower in September than July irrespective of plant age, which was reflected in lower larval performance of both herbivores in September. These results suggest that A. contorta invests in the chemical defenses of leaves especially at a young age, while the low nutritional value of leaves seems to limit the performance of leaf-chewing herbivores at the end of the season, regardless of plant age.
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Sericinus montela, a globally threatened butterfly species, feeds exclusively on Aristolochia contorta (Northern pipevine). Field surveys and glasshouse experiments were conducted to obtain a better understanding of the relationship between the two species. Interviews with the persons concerned with A. contorta were conducted to collect information about the site management measures. We found that management practices to control invasive species and manage the riverine areas might reduce the coverage of A. contorta and the number of eggs and larvae of S. montela. Our results indicated that the degraded quality of A. contorta may result in a decrease in S. montela populations by diminishing their food source and spawning sites. This study implies that ecological management in the riverine area should be set up to protect rare species and biodiversity.
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Aristolochia , Borboletas , Mariposas , Animais , Humanos , Larva , Atividades HumanasRESUMO
Exercise is an effective intervention to ameliorate metabolic diseases including obesity and insulin resistance, but the mechanisms involved in the metabolic amelioration have not yet been fully elucidated. This study aimed to determine whether AMPK-SIRT1-PGC-1α-FNDC5/Irisin-UCP1 expression is activated and whether metabolic dysfunction is ameliorated by chronic voluntary wheel running (VWR) in high-fat diet (HFD) induced obese mice. C57BL6J mice were randomly assigned into three groups at the age of 7 weeks for 10 weeks: normal chow diet (CON) group, HFD group, and HFD + VWR group. Chronic VWR ameliorates metabolic parameters and leads to increases in the expression of PGC-1α in the gastrocnemius muscle in HFD-induced obese mice. In contrast, the expression of AMPKα, SIRT1, and FNDC5, or circulating irisin levels did not lead to alteration. Improvement of metabolic health was partly mediated via PGC-1α expression by chronic VWR, but not FNDC5/Irisin pathway in HFD-induced obese mice.
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Dieta Hiperlipídica , Fibronectinas , Animais , Camundongos , Fibronectinas/metabolismo , Camundongos Obesos , Atividade Motora , Sirtuína 1 , Fatores de Transcrição/metabolismoRESUMO
Molecular profiling of the hypothalamus in response to metabolic shifts is a critical cue to better understand the principle of the central control of whole-body energy metabolism. The transcriptional responses of the rodent hypothalamus to short-term calorie restriction have been documented. However, studies on the identification of hypothalamic secretory factors that potentially contribute to the control of appetite are lacking. In this study, we analyzed the differential expression of hypothalamic genes and compared the selected secretory factors from the fasted mice with those of fed control mice using bulk RNA-sequencing. We verified seven secretory genes that were significantly altered in the hypothalamus of fasted mice. In addition, we determined the response of secretory genes in cultured hypothalamic cells to treatment with ghrelin and leptin. The current study provides further insights into the neuronal response to food restriction at the molecular level and may be useful for understanding the hypothalamic control of appetite.
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Hipotálamo , Inanição , Camundongos , Animais , Hipotálamo/metabolismo , Leptina/metabolismo , Inanição/metabolismo , Apetite/fisiologia , Jejum/fisiologia , Grelina/metabolismo , Perfilação da Expressão GênicaRESUMO
OBJECTIVE: Thyroid transcription factor-1 (TTF-1), a homeodomain-containing transcription factor, is predominantly expressed in discrete areas of the hypothalamus, which acts as the central unit for the regulation of whole-body energy homeostasis. Current study designed to identify the roles of TTF-1 on the responsiveness of the hypothalamic circuit activity to circulating leptin and the development of obesity linked to the insensitivity of leptin. METHODS: We generated conditional knock-out mice by crossing TTF-1flox/flox mice with leptin receptor (ObRb)Cre or proopiomelanocortin (POMC)Cre transgenic mice to interrogate the contributions of TTF-1 in leptin signaling and activity. Changes of food intake, body weight and energy expenditure were evaluated in standard or high fat diet-treated transgenic mice by using an indirect calorimetry instrument. Molecular mechanism was elucidated with immunohistochemistry, immunoblotting, quantitative PCR, and promoter assays. RESULTS: The selective deletion of TTF-1 gene expression in cells expressing the ObRb or POMC enhanced the anorexigenic effects of leptin as well as the leptin-induced phosphorylation of STAT3. We further determined that TTF-1 inhibited the transcriptional activity of the ObRb gene. In line with these findings, the selective deletion of the TTF-1 gene in ObRb-positive cells led to protective effects against diet-induced obesity via the amelioration of leptin resistance. CONCLUSIONS: Collectively, these results suggest that hypothalamic TTF-1 participates in the development of obesity as a molecular component involved in the regulation of cellular leptin signaling and activity. Thus, TTF-1 may represent a therapeutic target for the treatment, prevention, and control of obesity.
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Leptina , Pró-Opiomelanocortina , Fator Nuclear 1 de Tireoide , Animais , Camundongos , Hipotálamo/metabolismo , Leptina/genética , Leptina/metabolismo , Camundongos Knockout , Obesidade/genética , Obesidade/metabolismo , Pró-Opiomelanocortina/metabolismo , Fator Nuclear 1 de Tireoide/genética , Fator Nuclear 1 de Tireoide/metabolismoRESUMO
Recent advances in optical clearing techniques have dramatically improved deep tissue imaging by reducing the obscuring effects of light scattering and absorption. However, these optical clearing methods require specialized equipment or a lengthy undertaking with complex protocols that can lead to sample volume changes and distortion. In addition, the imaging of cleared tissues has limitations, such as fluorescence bleaching, harmful and foul-smelling solutions, and the difficulty of handling samples in high-viscosity refractive index (RI) matching solutions. To address the various limitations of thick tissue imaging, we developed an Aqueous high refractive Index matching and tissue Clearing solution for Imaging (termed AICI) with a one-step tissue clearing protocol that was easily made at a reasonable price in our own laboratory without any equipment. AICI can rapidly clear a 1 mm thick brain slice within 90 min with simultaneous RI matching, low viscosity, and a high refractive index (RI = 1.466), allowing the imaging of the sample without additional processing. We compared AICI with commercially available RI matching solutions, including optical clear agents (OCAs), for tissue clearing. The viscosity of AICI is closer to that of water compared with other RI matching solutions, and there was a less than 2.3% expansion in the tissue linear morphology during 24 h exposure to AICI. Moreover, AICI remained fluid over 30 days of air exposure, and the EGFP fluorescence signal was only reduced to ~65% after 10 days. AICI showed a limited clearing of brain tissue >3 mm thick. However, fine neuronal structures, such as dendritic spines and axonal boutons, could still be imaged in thick brain slices treated with AICI. Therefore, AICI is useful not only for the three-dimensional (3D) high-resolution identification of neuronal structures, but also for the examination of multiple structural imaging by neuronal distribution, projection, and gene expression in deep brain tissue. AICI is applicable beyond the imaging of fluorescent antibodies and dyes, and can clear a variety of tissue types, making it broadly useful to researchers for optical imaging applications.
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Encéfalo , Imagem Óptica , Animais , Encéfalo/diagnóstico por imagem , Imunofluorescência , Imageamento Tridimensional/métodos , Camundongos , Neurônios , Imagem Óptica/métodos , RefratometriaRESUMO
Nutrient availability and utilization in hypothalamic cells are directly associated with the regulation of whole-body energy homeostasis. Thus, establishing metabolic profiling in the hypothalamus in response to metabolic shift is valuable to better understand the underlying mechanism of appetite regulation. In the present study, we evaluate the alteration of lipophilic and hydrophilic metabolites in both the hypothalamus and serum of fasted mice. Fasted mice displayed an elevated ketone body and decreased lactate levels in the hypothalamus. In support of the metabolite data, we further confirmed that short-term food deprivation resulted in the altered expression of genes involved in cellular metabolic processes, including the shuttling of fuel sources and the production of monocarboxylates in hypothalamic astrocytes. Overall, the current study provides useful information to close the gap in our understanding of the molecular and cellular mechanisms underlying hypothalamic control of whole-body energy metabolism.
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Effects of environmental change on plants can differ due to sequential changes in their life-history strategies (i.e., ontogenetic variations). The fitness of herbivorous insects by physiological changes of the host plant could be affected depending on their diet breadth. However, little is known regarding the combinational effects of plant ontogeny and climate change on plant-herbivore interactions. This study examined the plant ontogeny-dependent effects of climate change on the interaction between a host plant (Aristolochia contorta), its specialist herbivore (Sericinus montela), and a generalist herbivore (Spodoptera exigua). Plants were grown under a factorial design of two distinct CO2 concentrations (ambient, 400 ppm; elevated, 560 ppm) and two watering frequencies (control, once a week; increased, twice a week). Plant ontogeny ameliorated the effects of climate change by altering its defensive traits, where nutrient-related factors were cumulatively affected by climate change. Herbivore performance was assessed at three different plant ontogenetic stages (1st-year juvenile, 1st-year senescence, and 2nd-year juvenile). Elevated CO2 levels reduced the growth and survival of the specialist herbivore, whereas increased watering frequency partially alleviated this reduced performance. Generalist herbivore performance slightly increased under elevated CO2 levels with progressing ontogenetic stages. The effects of climate change, both elevated CO2 and increased watering frequency were weaker in 2nd-year juveniles than in 1st-year juveniles. Elevated CO2 levels detrimentally affected the nutritional quality of A. contorta leaves. The effects of climate change on both specialist and generalist herbivore performance differed as plant ontogenetic stage proceeded. Increased growth rates and survival of the generalist herbivore at the latter ontogenetic stage might negatively affect the population dynamics of a specialist herbivore. This study suggests that biases are possible when the plant-herbivore interaction under a changing environment is predicted from a singular plant ontogenetic stage.
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Aristolochia , Herbivoria , Animais , Dióxido de Carbono/farmacologia , Insetos/fisiologia , Folhas de Planta/fisiologia , PlantasRESUMO
The hypothalamic arcuate nucleus (Arc) is a central unit that controls the appetite through the integration of metabolic, hormonal, and neuronal afferent inputs. Agouti-related protein (AgRP), proopiomelanocortin (POMC), and dopaminergic neurons in the Arc differentially regulate feeding behaviors in response to hunger, satiety, and appetite, respectively. At the time of writing, the anatomical and electrophysiological characterization of these three neurons has not yet been intensively explored. Here, we interrogated the overall characterization of AgRP, POMC, and dopaminergic neurons using genetic mouse models, immunohistochemistry, and whole-cell patch recordings. We identified the distinct geographical location and intrinsic properties of each neuron in the Arc with the transgenic lines labelled with cell-specific reporter proteins. Moreover, AgRP, POMC, and dopaminergic neurons had different firing activities to ghrelin and leptin treatments. Ghrelin led to the increased firing rate of dopaminergic and AgRP neurons, and the decreased firing rate of POMC. In sharp contrast, leptin resulted in the decreased firing rate of AgRP neurons and the increased firing rate of POMC neurons, while it did not change the firing rate of dopaminergic neurons in Arc. These findings demonstrate the anatomical and physiological uniqueness of three hypothalamic Arc neurons to appetite control.
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Núcleo Arqueado do Hipotálamo , Pró-Opiomelanocortina , Proteína Relacionada com Agouti/genética , Animais , Apetite , Núcleo Arqueado do Hipotálamo/metabolismo , Grelina/metabolismo , Grelina/farmacologia , Leptina/metabolismo , Camundongos , Neurônios/metabolismo , Pró-Opiomelanocortina/genéticaRESUMO
Metabolic abnormalities are tightly connected to the perturbation of normal brain functions, thereby causing multiple neurodegenerative diseases. The hypothalamus is the master unit that controls the whole-body energy homeostasis. Thus, altered metabolic activity in the hypothalamus could be a crucial clue to better understand the development of metabolic disorders during aging. The current study aimed to investigate the changes in hypothalamic metabolites according to the aging process using gas chromatography-mass spectrometry. We identified that multiple metabolites and neurotransmitters were effectively reduced in the hypothalamus of aged mice. In addition, we observed increased levels of genes linked to the production and utilization of monocarboxylates in the aged hypothalamus, indicating the initiation of metabolic activity to produce alternative nutrient sources. Lastly, we found a reduced number of astrocytes in the hypothalamus of aged mice, suggesting that reduced nutrient availability in the hypothalamus might be associated with the decreased activity of astrocytes during aging. Collectively, the present study suggests that the deterioration of metabolic activities in the hypothalamus might be a primary cause and/or outcome of metabolic diseases associated with the aging process.