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deciphering the role of PGC-1α in neurological disorders: from mitochondrial dysfunction to synaptic failure

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Neural Regeneration Research 2022年第2期17卷 237-245页

作者： Jessica D.Panes Aline Wendt Oscar Ramirez-Molina Patricio A.Castro Jorge Fuentealba Laboratorio de Screening de Compuestos Neuroactivos(LSCN) Departamento de FisiologiaFacultad de Ciencias BiologicasUniversidad de ConcepcionConcepcionChile Centro de Investigaciones Avanzadas en Biomedicina(CIAB-UdeC) Facultad de Ciencias BiologicasUniversidad de ConcepcionConcepcionChile departamento de fisiologia Facultad de Ciencias BiologicasUniversidad de ConcepcionConcepcionChile

The onset and mechanisms underlying neurodegenerative diseases remain uncertain. The main features of neurodegenerative diseases have been related with cellular and molecular events like neuronal loss, mitochondrial dysfunction and aberrant accumulation of misfolded proteins or peptides in specific areas of the brain. The most prevalent neurodegenerative diseases belonging to age-related pathologies are Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Interestingly, mitochondrial dysfunction has been observed to occur during the early onset of several neuropathological events associated to neurodegenerative diseases. The master regulator of mitochondrial quality control and energetic metabolism is the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α). Additionally, it has been observed that PGC-1α appears to be a key factor in maintaining neuronal survival and synaptic transmission. In fact, PGC-1α downregulation in different brain areas(hippocampus, substantia nigra, cortex, striatum and spinal cord) that occurs in function of neurological damage including oxidative stress, neuronal loss, and motor disorders has been seen in several animal and cellular models of neurodegenerative diseases. Current evidence indicates that PGC-1α upregulation may serve as a potent therapeutic approach against development and progression of neuronal damage. Remarkably, increasing evidence shows that PGC-1α deficient mice have neurodegenerative diseases-like features, as well as neurological abnormalities. Finally, we discuss recent studies showing novel specific PGC-1α isoforms in the central nervous system that appear to exert a key role in the age of onset of neurodegenerative diseases and have a neuroprotective function in the central nervous system, thus opening a new molecular strategy for treatment of neurodegenerative diseases. The purpose of this review is to provide an up-t

关键词： Alzheimer's disease amyotrophic lateral sclerosis Huntington's disease mitochondrial dysfunction Parkinson's disease PGC-1α synaptic function vascular dementia

cAMP:A second messenger involved in the mechanism of midgut alkalinization in Lutzomyia longipalpis

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Insect Science 2022年第4期29卷 1059-1070页

作者： denise Barguil Nepomuceno Grasielle Caldas D’Ávila Pessoa Leonardo Barbosa Koerich Marcos Horácio Pereira Mauricio Roberto Viana Sant'Anna Ricardo Nascimento Araújo Nelder Figueiredo Gontijo Laboratório de fisiologia de Insetos Hematófagos Departamento de Parasitologia/ICBUniversidade Federal de Minas GeraisBelo HorizonteMGBrazil

The sand fly Lutzomyia longipalpis is the main vector of Leishmania infantum in the *** sand flies ingest sugar-rich solutions and blood,which are digested in the *** of nutrients is an essential function performed by digestive enzymes,which require appropriate physiological *** of the main aspects that influence enzymatic activity is the gut pH,which must be tightly *** second messengers are frequently involved in the coordination of tightly regulated physiological events,we investigated if the second messenger cAMP would participate in the process of alkalinization in the abdominal midgut of female *** midguts containing the indicator dye bromothymol-blue,cAMP stimulated the alkalinization of the midgut *** another technique based on the use of fluorescein as a pH indicator,we propose that cAMP is involved in the alkalinization of the midgut by activating HCO3-transport from the enterocyte's cytoplasm to the *** results strongly suggested that the carrier responsible for this process would be a HCO3−/Cl−antiporter located in the enterocytes’apical *** promotes the release of alkalinizing hormones in the hemolymph;however,when the enzyme adenylyl cyclase,responsible for cAMP production,was inhibited,we observed that the hemolymph from blood-fed ***’females did not stimulate midgut *** result indicated that hormone-stimulated alkalinization is mediated by *** the present study,we provide evidences that cAMP has a key role in the control of intestinal pH.

关键词： abdominal midgut alkalinization cAMP HCO_(3)^(-)/Cl^(-)antiport hormone Lulcomyia longipalpis

The Periaqueductal Gray and Its Extended Participation in Drug Addiction Phenomena

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Neuroscience Bulletin 2021年第10期37卷 1493-1509页

作者： Priscila Vazquez-Leon Abraham Miranda-Paez Jesus Chavez-Reyes Gonzalo Allende Paulino Barragan-Iglesias Bruno A.Marichal-Cancino departamento de fisiologia y Farmacologia Centro de Ciencias BasicasUniversidad Autonoma de AguascalientesCiudad Universitaria20131 AguascalientesAgs.Mexico departamento de fisiologia Escuela Nacional de Ciencias BiologicasInstituto Politecnico NacionalWilfrido Massieu esq.Manuel Stampa s/n Col.Nueva Industrial Vallejo07738 Gustavo A.MaderoMexico CityMexico

The periaqueductal gray(PAG)is a complex mesencephalic structure involved in the integration and execution of active and passive self-protective behaviors against imminent threats,such as immobility or flight from a *** activity is also associated with the integration of responses against physical discomfort(e.g.,anxiety,fear,pain,and disgust)which occurs prior an imminent attack,but also during withdrawal from drugs such as morphine and *** PAG sends and receives projections to and from other well-documented nuclei linked to the phenomenon of drug addiction including:(i)the ventral tegmental area;(ii)extended amygdala;(iii)medial prefrontal cortex;(iv)pontine nucleus;(v)bed nucleus of the stria terminalis;and(vi)*** models have suggested that the PAG contributes to the modulation of anxiety,fear,and nociception(all of which may produce physical discomfort)linked with chronic exposure to drugs of *** produced by the major pharmacological classes of drugs of abuse is mediated through actions that include participation of the *** support of this,there is evidence of functional,pharmacological,***/or genetic alterations in the PAG during the impulsive/compulsive intake or withdrawal from a *** to its small size,it is difficult to assess the anatomical participation of the PAG when using classical neuroimaging techniques,so its phys-iopathology in drug addiction has been underestimated and poorly *** this theoretical review,we discuss the involvement of the PAG in drug addiction mainly via its role as an integrator of responses to the physical discomfort associated with drug withdrawal.

关键词： Periaqueductal gray Reward circuit Antireward circuit Alcohol Caffeine Cannabis Opioids Stimulants

Anti-inflammatory intestinal activity of Combretum duarteanum Cambess. in trinitrobenzene sulfonic acid colitis model

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World Journal of Gastroenterology 2017年第8期23卷 1353-1366页

作者： Gedson Rodrigues de Morais Lima Flavia Danniele Frota MachadoLarissa Lucena Périco Felipe Meira de Faria Anderson Luiz-Ferreira Alba Regina Monteiro Souza Brito Cláudia Helena Pellizzon Clélia Akiko Hiruma-Lima Josean Fechine Tavares JoséMaria Barbosa Filho LeOnia Maria Batista departamento de Ciências Farmacêuticas Centro de Ciências da SaúdeLaboratório de Farmacologia do Trato GastrintestinalUniversidade Federal da Paraíba(UFPB)Cidade Universitária departamento de fisiologia Instituto de BiociênciasUniversidade Estadual Paulista departamento de Biologia Estrutural e Funcional Instituto de BiologiaUniversidade Estadual de Campinas(UNICAMP departamento de Ciencias Biológicas Instituto de BiotecnologiaUniversidade Federal de Goiás departamento de Morfologia Instituto de BiociênciasUniversidade Estadual Paulista

To evaluate the anti-inflammatory intestinal effect of the ethanolic extract (EtOHE) and hexane phase (HexP) obtained from the leaves of Combretum duarteanum (Cd).METHODSInflammatory bowel disease was induced using trinitrobenzenesulfonic acid in acute and relapsed ulcerative colitis in rat models. Damage scores, and biochemical, histological and immunohistochemical parameters were *** Cd-EtOHE and Cd-HexP caused significant reductions in macroscopic lesion scores and ulcerative lesion areas. The vegetable samples inhibited myeloperoxidase increase, as well as pro-inflammatory cytokines TNF-α and IL-1β. Anti-inflammatory cytokine IL-10 also increased in animals treated with the tested plant samples. The anti-inflammatory intestinal effect is related to decreased expression of cyclooxygenase-2, proliferating cell nuclear antigen, and an increase in superoxide *** data indicate anti-inflammatory intestinal activity. The effects may also involve participation of the antioxidant system and principal cytokines relating to inflammatory bowel disease.

关键词： Combretum duarteanum Medicinal plants Combretaceae Inflammatory bowel disease Anti-inflammatory intestinal activity

Chronic model of tympanic perforation in rats with mitomycin C and dexamethasone

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Journal of Otology 2019年第1期14卷 12-16页

作者： Tomás Esteban Noemí M.Atucha Jose María Moraleda Joaquín Garcia-Esta? Carmen L.Insausti Javier Moraleda-deleyto Servicio de Otorinolaringologia Hospital General Universitario Santa Lucia departamento de fisiologia Facultad de Medicina Universidad de Murcia Instituto Murciano de Investigacion Biosanitaria departamento de Medicina Facultad de Medicina Universidad de MurciaInstituto Murciano de Investigacion Biosanitaria ENT Service University Hospital of Lewisham

A rat model of chronic tympanic membrane perforation was developed to be used in the search of new materials for the sealing of these perforations. A longitudinal study was carried out in rats subjected to incisional myr-ingotomy followed by the application of mitomycin C alone or with dexamethasone. Rats were checked at days 3, 7,1 0,1 4 and weekly thereafter until perforation closure, for up to 6 months. The addition of dexamethasone is a key component in order to obtain a chronic opening. Myringotomies treated w ith saline had a mean healing time of 8.5 days. At 8 weeks, between 62.5% and 77.7% of tympanic membranes treated w ith mitomycin C and dexamethasone remained perforated and at 6 months this number fell to 21.4%. This technique is able to maintain most tympanic membrane perforations patent for at least 8 weeks. This rat model is adequate for its use in preclinical or translational research.

关键词： Animal model Chronic tympanic membrane perforation Mitomycin C Myringotomy dexamethasone

Central depressant effects of Piper tuberculatum Jacq essential oil in mice

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Food Bioscience 2022年第4期48卷 620-629页

作者： Valterlúcio dos Santos Sales Francisco Romero Cabral Emmily Petícia do Nascimento Sales Tatyelle Bezerra Carvalho Maria Haiele Nogueira Costa Victor Afonso Pereira de Oliveira Cristina Kelly de Souza Rodrigues Francisco Rodolpho Sobreira Dantas Nobrega de Figueiredo Daniel Souza Bezerra Gyllyandeson de Araújo delmondes Henrique Douglas Melo Coutinho Jose Galberto Martins da Costa Irwin Rose Alencar de Menezes Cícero Francisco Bezerra Felipe Marta Regina Kerntopf Universidade Regional do Cariri Departamento de Química Biol´ogicaCratoCear´aBrazil Universidade Federal de S˜ao Paulo-departamento de fisiologia S˜ao PauloSPBrazil Faculdade de Ciˆencias M´edicas da Santa Casa de S˜ao Paulo S˜ao PauloSPBrazil Universidade Federal da Paraíba Departamento de Biologia MolecularJo˜ao PessoaParaíbaBrazil

This study aims to investigate the toxicity and possible effects and mechanism of action of the essential oil obtained from the Piper tuberculatum Jacq.‘s fruit(EOPT)on the central nervous system(CNS)of *** the Hippocratic test,it was observed ambulation reduction,sedation,piloerection and mortality of 25%at the dose of 1000 mg/kg and 50%at the dose of 5000 mg/*** results found demonstrate that the EOPT is endowed with a possible depressant effect,and is characterized by a likely sedative(open field test),anxiolytic-like(elevated plus maze test),anticonvulsant(pentylenetetrazole-induced seizure test)and hypnotic action(pentobarbital-induced sleeping time).These effects may possibly occur due to the interaction between the monoterpenes,present in its essential oil,and the GABAergic pathway confirmed by reversion of the effects by ***,these results demonstrate the therapeutic potential and the validation of the ethnopharmacological use of this species in the treatment of disorders affecting the central nervous system.

关键词： Piper tuberculatum Jacq. Essential oil Sedative Anxiolytic Hypnotic

Classical olfactory conditioning promotes long-term memory and improves odor-cued flight orientation in the South American native bumblebee Bombus pauloensis

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Current Zoology 2021年第5期67卷 561-563页

作者： denise NERY Florencia PALOTTINI Walter M.FARINA Laboratorio de Insectos Sociales Departamento de Biodiversidad y Biologia ExperimentalFacultad de Ciencias NaturalesUniversidad de Buenos AiresBuenos AiresArgentina Instituto de fisiologia Biologia Molecular y Neurociencias(IFIBYNE)CONICET-Universidad de Buenos AiresBuenos AiresArgentina

When collecting a flower,bumblebees learn to associate floral features with reward,preferring,and specializing in the most profitable ones they visit(Chittka et al.1999).The proboscis extension reflex(PER)occurs naturally in the feeding context allowing individuals to access the floral *** controlled conditions,the PER paradigm is a well-established controlled learning procedure used in honeybees(Takeda 1961),and some bumblebees of the genus Bombus(Laloi et al.1999).The assessment of cognitive capacities in an operant context has been studied mainly in *** and ***(Chittka 1998;Mirwan and Kevan 2014).However,little is known about the ability to evoke associative memories in an operant context,which had been acquired in a classical *** turn,on the contrary,the Bombus genus also has the capacity to form longterm memories(Chittka 1998;McAulay et al.2015).In particular,the South American bumblebee ***(***)can learn a pure odor when it is presented in a paired association with a sugar reward within a PER paradigm(Palottini et al.2018).As other species,this one is a commercially reared pollinator that is increasingly managed in pollination services of some South American countries and they could be important for increasing production of crops(Palottini et al.2018).

关键词： crops sugar associative

Bone marrow-derived monocyte infusion improves hepatic fibrosis by decreasing osteopontin,TGF-β1,IL-13 and oxidative stress

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World Journal of Gastroenterology 2017年第28期23卷 5146-5157页

作者： Veruska Cintia Alexandrino de Souza Thiago Almeida Pereira Valéria Wanderley Teixeira Helotonio Carvalho Maria Carolina Accioly Brelaz de Castro Carolline Guimaraes D’assuncao Andreia Ferreira de Barros Camila Lima Carvalho Virgínia Maria Barros de Lorena Vláudia Maria Assis Costa Alvaro Aguiar Coelho Teixeira Regina Celia Bressan Queiroz Figueiredo Sheilla Andrade de Oliveira Centro de Pesquisas Aggeu Magalhaes Fundacao Oswaldo Cruz Immunopathogenesis Section Laboratory of Parasitic DiseasesNational Institute of Allergy and Infectious DiseaseNational Institutes of HealthBethesdaMDUSA and Laboratório de Doencas Parasitárias e infecciosasFaculdade de MedicinaUniversidade Federal de Minas Gerais departamento de Morfologia e fisiologia Animal Universidade Federal Rural de Pernambuco departamento de Biofísica e Radiobiologia Universidade Federal de Pernambuco Centro Acadêmico de Vitória Universidade Federal de Pernambuco departamento de Medicina Tropical Universidade Federal de Pernambuco

To evaluate the therapeutic effects of bone marrow-derived CD11b+CD14+ monocytes in a murine model of chronic liver *** liver damage was induced in C57BL/6 mice by administration of carbon tetrachloride and ethanol for 6 mo. Bone marrow-derived monocytes isolated by immunomagnetic separation were used for therapy. The cell transplantation effects were evaluated by morphometry, biochemical assessment, immunohistochemistry and enzyme-linked immunosorbent ***11b+CD14+ monocyte therapy significantly reduced liver fibrosis and increased hepatic glutathione levels. Levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6 and IL-1β, in addition to pro-fibrotic factors, such as IL-13, transforming growth factor-β1 and tissue inhibitor of metalloproteinase-1 also decreased, while IL-10 and matrix metalloproteinase-9 increased in the monocyte-treated group. CD11b+CD14+ monocyte transplantation caused significant changes in the hepatic expression of α-smooth muscle actin and *** therapy is capable of bringing about improvement of liver fibrosis by reducing oxidative stress and inflammation, as well as increasing anti-fibrogenic factors.

关键词： Monocytes Bone marrow mononuclear cells Cell therapy Macrophages Glutathione Liver fibrosis

Antioxidant properties of glutamine and its role in VEGF-Akt pathways in portal hypertension gastropathy

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World Journal of Gastroenterology 2013年第28期19卷 4464-4474页

作者： Camila Marques Francielli Licks Ingrid Zattoni Beatriz Borges Luiz Eduardo Rizzo de Souza Claudio Augusto Marroni Norma Possa Marroni Universidade Federal do Rio Grande do Sul-PPG fisiologia Porto Alegre 90000100 Brazil Universidade Federal do Paraná Curitiba 81531900 Brazil departamento de Medicina Interna-Gastroenterologia-Universidade Federal de Ciências da Saúde de Porto Alegre Porto Alegre 90000100 Brazil Universidade Federal do Rio Grande do Sul-PPG fisiologia Universidade Luterana do Brasil Porto Alegre 90000100 Brazil

AIM: To investigate the effects of glutamine on oxidative/nitrosative stress and the vascular endothelial growth factor (VEGF)-Akt-endothelial nitric oxide synthase (eNOS) signaling pathway in an experimental model of portal hypertension induced by partial portal vein ligation (PPVL). METHODS: Portal hypertension was induced by PPVL. The PPVL model consists of a partial obstruction of the portal vein, performed using a 20 G blunt needle as a guide, which is gently removed after the procedure. PPVL model was performed for 14 d beginning treatment with glutamine on the seventh day. On the fifteenth day, the mesenteric vein pressure was checked and the stomach was removed to test immunoreactivity and oxidative stress markers. We evaluated the expression and the immunoreactivity of proteins involved in the VEGF-Akt-eNOS pathway by Western blotting and immunohistochemical analysis. Oxidative stress was measured by quantification of the cytosolic concentration of thiobarbituric acid reactive substances (TBARS) as well as the levels of total glutathione (GSH), superoxide dismutase (SOD) activity, nitric oxide (NO) production and nitrotyrosine immunoreactivity. RESULTS: All data are presented as the mean ± SE. The production of TBARS and NO was significantly increased in PPVL animals. A reduction of SOD activity was detected in PPVL + G group. In the immunohistochemical analyses of nitrotyrosine, Akt and eNOS, the PPVL group exhibited significant increases, whereas decreases were observed in the PPVL + G group, but no difference in VEGF was detected between these groups. Western blotting analysis detected increased expression of phosphatidylinositol-3-kinase (PI3K), P-Akt and eNOS in the PPVL group compared with the PPVL + G group, which was not observed for the expression of VEGF when comparing these groups. Glutamine administration markedly alleviated oxidative/nitrosative stress, normalized SOD activity, increased levels of total GSH and blocked NO overproduction as well

关键词： Partial portal vein ligation Oxidative stress Glutamine Portal hypertension Rats