RESUMO
Chronic metabolic alterations may represent a risk factor for the development of cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and obesity are known to imprint epigenetic markers that compromise the proper expression of cell survival genes. Here, we showed that chronic hyperglycemia (60 days) induced by a single intraperitoneal injection of streptozotocin compromised cognition by reducing hippocampal ERK signaling and by inducing neurotoxicity in rats. The mechanisms appear to be linked to reduced active DNA demethylation and diminished expression of the neuroprotective transcription factor REST. The impact of the relationship between adiposity and DNA hypermethylation on REST expression was also demonstrated in peripheral blood mononuclear cells in obese children with reduced levels of blood ascorbate. The reversible nature of epigenetic modifications and the cognitive impairment reported in obese children, adolescents, and adults suggest that the correction of the anthropometry and the peripheral metabolic alterations would protect brain homeostasis and reduce the risk of developing neurodegenerative diseases.
Assuntos
Transtornos Cognitivos/etiologia , Diabetes Mellitus Experimental/complicações , Hipocampo/metabolismo , Hiperglicemia/complicações , Proteínas Repressoras/metabolismo , Animais , Aprendizagem da Esquiva/fisiologia , Transtornos Cognitivos/genética , Transtornos Cognitivos/metabolismo , Metilação de DNA , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Humanos , Hiperglicemia/genética , Hiperglicemia/metabolismo , Aprendizagem em Labirinto/fisiologia , Ratos , Proteínas Repressoras/genéticaRESUMO
Parkinson's disease (PD), the second-most prevalent neurodegenerative disease, is primarily characterized by neurodegeneration in the substantia nigra pars compacta, resulting in motor impairment. Loss-of-function mutations in parkin are the major cause of the early onset familial form of the disease. Although rodents deficient in parkin (parkin(-/-) ) have some dopaminergic system dysfunction associated with central oxidative stress and energy metabolism deficiencies, these animals only display nigrostriatal pathway degeneration under inflammatory conditions. This study investigated the impact of the inflammatory stimulus induced by lypopolisaccharide (LPS) on tetrahydrobiopterin (BH4) synthesizing enzymes (de novo and salvage pathways), since this cofactor is essential for dopamine synthesis. The mitochondrial content and architecture was investigated in the striatum of LPS-exposed parkin(-/-) mice. As expected, the LPS (0.33 mg/kg; i.p.) challenge compromised spontaneous locomotion and social interaction with juvenile parkin(-/-) and WT mice. Moreover, the genotype impacted the kinetics of the investigation of the juvenile. The inflammatory scenario did not induce apparent changes in mitochondrial ultrastructure; however, it increased the quantity of mitochondria, which were of smaller size, and provoked the perinuclear distribution of the organelle. Furthermore, the BH4 de novo biosynthetic pathway failed to be up-regulated in the LPS challenge, a well-known stimulus for its activation. The LPS treatment increased sepiapterin reductase (SPR) expression, suggesting compensation by the salvage pathway. This might indicate that dopamine synthesis is compromised in parkin(-/-) mice under inflammatory conditions. Finally, this scenario impaired the striatal expression of the transcription factor BDNF, possibly favoring cell death.
Assuntos
Biopterinas/análogos & derivados , Corpo Estriado/metabolismo , Ubiquitina-Proteína Ligases/genética , Oxirredutases do Álcool/metabolismo , Animais , Comportamento Animal , Biopterinas/biossíntese , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Lipopolissacarídeos/farmacologia , Locomoção , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Plasticidade Neuronal/fisiologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/veterinária , Ubiquitina-Proteína Ligases/deficiência , Regulação para Cima/efeitos dos fármacosRESUMO
The cellular transformation of normal functional cells to neoplastic ones implies alterations in the cellular metabolism and mitochondrial function in order to provide the bioenergetics and growth requirements for tumour growth progression. Currently, the mitochondrial physiology and dynamic shift during pituitary tumour development are not well understood. Pituitary tumours present endocrine neoplastic benign growth which, in previous reports, we had shown that in addition to increased proliferation, these tumours were also characterized by cellular senescence signs with no indication of apoptosis. Here, we show clear evidence of oxidative stress in pituitary cells, accompanied by bigger and round mitochondria during tumour development, associated with augmented biogenesis and an increased fusion process. An activation of the Nrf2 stress response pathway together with the attenuation of the oxidative damage signs occurring during tumour development were also observed which will probably provide survival advantages to the pituitary cells. These neoplasms also presented a progressive increase in lactate production, suggesting a metabolic shift towards glycolysis metabolism. These findings might imply an oxidative stress state that could impact on the pathogenesis of pituitary tumours. These data may also reflect that pituitary cells can modulate their metabolism to adapt to different energy requirements and signalling events in a pathophysiological situation to obtain protection from damage and enhance their survival chances. Thus, we suggest that mitochondria function, oxidative stress or damage might play a critical role in pituitary tumour progression.
Assuntos
Transformação Celular Neoplásica/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Neoplasias Hipofisárias/metabolismo , Adaptação Fisiológica/fisiologia , Animais , Antioxidantes/metabolismo , Metabolismo Energético/fisiologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Interictal hypometabolism is commonly measured by 18-fluoro-deoxyglucose Positron Emission Tomography (FDG-PET) in the temporal lobe of patients with mesial temporal lobe epilepsy (MTLE-HS). Left temporal lobe interictal FDG-PET hypometabolism has been associated with verbal memory impairment, while right temporal lobe FDG-PET hypometabolism is associated with nonverbal memory impairment. The biochemical mechanisms involved in these findings remain unknown. In comparison to healthy controls (n=21), surgically treated patients with MTLE-HS (n=32, left side=17) had significant lower scores in the Rey Auditory Verbal Learning Test (RAVLT retention and delayed), Logical Memory II (LMII), Boston Naming test (BNT), Letter Fluency and Category Fluency. We investigated whether enzymatic activities of the mitochondrial enzymes Complex I (C I), Complex II (C II), Complex IV (C IV) and Succinate Dehydrogenase (SDH) from the resected samples of the middle temporal neocortex (mTCx), amygdala (AMY) and hippocampus (HIP) were associated with performance in the RAVLT, LMII, BNT and fluency tests of our patients. After controlling for the side of hippocampus sclerosis, years of education, disease duration, antiepileptic treatment and seizure outcome after surgery, no independent associations were observed between the cognitive test scores and the analyzed mitochondrial enzymatic activities (p>0.37). Results indicate that memory and language impairment observed in MTLE-HS patients are not strongly associated with the levels of mitochondrial CI, CII, SDH and C IV enzymatic activities in the temporal lobe structures ipsilateral to the HS lesion.
Assuntos
Encéfalo/metabolismo , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/patologia , Transtornos da Memória/etiologia , Complexos Multienzimáticos/metabolismo , Adulto , Anticonvulsivantes/uso terapêutico , Encéfalo/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Eletroencefalografia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/tratamento farmacológico , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Transtornos da Memória/diagnóstico por imagem , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Estatísticas não ParamétricasAssuntos
Epilepsia Resistente a Medicamentos/enzimologia , Epilepsia do Lobo Temporal/enzimologia , Sistema Límbico/enzimologia , Transtornos Mentais/enzimologia , Mitocôndrias/enzimologia , Complexos Multienzimáticos/metabolismo , Adulto , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/psicologia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/psicologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Sistema Límbico/patologia , Sistema Límbico/cirurgia , Masculino , Transtornos Mentais/complicações , Neocórtex/enzimologia , Neocórtex/cirurgia , Dados Preliminares , Estudos Prospectivos , Esclerose/enzimologia , Esclerose/patologia , Esclerose/psicologia , Esclerose/cirurgia , Lobo Temporal/enzimologia , Lobo Temporal/cirurgiaRESUMO
Ultraviolet-B radiation (UVBR) affects plants in many important ways, including reduction of growth rate and primary productivity, and changes in ultrastructures. Rice (Oryza sativa) is one of the most cultivated cereals in the world, along with corn and wheat, representing over 50% of agricultural production. In this study, we examined O. sativa plants exposed to ambient outdoor radiation and laboratory-controlled photosynthetically active radiation (PAR) and PAR + UVBR conditions for 2 h/day during 30 days of cultivation. The samples were studied for morphological and ultrastructural characteristics, and physiological parameters. PAR + UVBR caused changes in the ultrastructure of leaf of O. sativa and leaf morphology (leaf index, leaf area and specific leaf area, trichomes, and papillae), plant biomass (dry and fresh weight), photosynthetic pigments, phenolic compounds, and protein content. As a photoprotective acclimation strategy against PAR + UVBR damage, an increase of 66.24% in phenolic compounds was observed. Furthermore, PAR + UVBR treatment altering the levels of chlorophylls a and b, and total chlorophyll. In addition, total carotenoid contents decreased after PAR + UVBR treatment. The results strongly suggested that PAR + UVBR negatively affects the ultrastructure, morphology, photosynthetic pigments, and growth rates of leaf of O. sativa and, in the long term, it could affect the viability of this economically important plant.
Assuntos
Oryza/fisiologia , Oryza/ultraestrutura , Raios Ultravioleta , Oryza/efeitos da radiação , Fotossíntese/efeitos da radiação , Pigmentos Biológicos/metabolismo , Epiderme Vegetal/citologia , Epiderme Vegetal/efeitos da radiação , Epiderme Vegetal/ultraestrutura , Folhas de Planta/anatomia & histologia , Folhas de Planta/efeitos da radiação , Proteínas de Plantas/metabolismo , Polifenóis/metabolismo , SolubilidadeRESUMO
The in vivo effect of ultraviolet radiation-B (UVBR) in apical segments of Chondracanthus teedei was examined. Over a period of 7 days, the segments were cultivated and exposed to photosynthetically active radiation (PAR) at 80 µmol photons m(-2) s(-1) and PAR + UVBR at 1.6 W m(-2) for 3 h per day. The samples were processed for electron microscopy and histochemistry; also was analyzed growth rates, mitochondrial activity, protein levels, content of photosynthetic pigments and photosynthetic performance. UVBR elicited increased cell wall thickness and accumulation of plastoglobuli, changes in mitochondrial organization and destruction of chloroplast internal organization. Compared to controls, algae exposed to PAR + UVBR showed a growth rate reduction of 55%. The content of photosynthetic pigments, including chlorophyll a and phycobiliproteins, decreased after exposure to PAR + UVBR. This result agrees with the decreased photosynthetic performance observed after exposing algae to PAR + UVBR. Irradiation also elicited increased activity of the antioxidant enzyme glutathione peroxidase and decreased mitochondrial NADH dehydrogenase activity, which correlated with the decreased protein content in plants exposed to PAR + UVBR. Taken together, these findings strongly indicate that UVBR negatively affects the architecture and metabolism of the carragenophyte C. teedei.