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1.
Res Aging ; 45(5-6): 410-422, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35503011

RESUMO

Global events that prime thoughts of proximity to death (e.g., the COVID-19 pandemic) can compress individuals' perceptions of future time horizons, and previous studies have found that compressed time horizons can be beneficial for older adults' well-being. However, findings from recent studies are mixed, and studies of well-being during the early months of COVID-19 show that older adults have fared comparatively well. The current study examines relationships between Future Time Perspective (FTP), COVID-19 impact, and purpose in life (PIL) among older Canadian women (N = 190; ages 59+). We expected that total FTP would be positively associated with PIL but that FTP subscales would be associated with PIL in different ways; COVID-19 impact would not be associated with PIL, but COVID-19 impact would moderate the FTP-PIL relationship. We found partial support for these hypotheses, as well as prevalence of social connection themes in open-ended question responses regarding COVID-19 impact.


Assuntos
COVID-19 , Pandemias , Humanos , Feminino , Idoso , Canadá , Tempo
2.
BMC Neurosci ; 10: 130, 2009 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-19860916

RESUMO

BACKGROUND: Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U) associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival. RESULTS: In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months). This is mediated at least in part through an anti-apoptotic mechanism. Control cells, while expressing basal levels of progranulin do not survive in serum free conditions. Knockdown of progranulin expression using shRNA technology further reduced cell survival. CONCLUSION: Neurons are among the most long-lived cells in the body and are subject to low levels of toxic challenges throughout life. We have demonstrated that progranulin is abundantly expressed in motor neurons and is cytoprotective over prolonged periods when over-expressed in a neuronal cell line. This work highlights the importance of progranulin as neuroprotective growth factor and may represent a therapeutic target for neurodegenerative diseases including motor neuron disease.


Assuntos
Sobrevivência Celular/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neurônios Motores/metabolismo , Medula Espinal/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Western Blotting , Linhagem Celular , Proliferação de Células , Sobrevivência Celular/genética , Células Cultivadas , Clonagem Molecular , Imunofluorescência , Gânglios Espinais/metabolismo , Gânglios Espinais/ultraestrutura , Complexo de Golgi/metabolismo , Complexo de Golgi/ultraestrutura , Granulinas , Humanos , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Camundongos , Microscopia Confocal , Neurônios Motores/ultraestrutura , Progranulinas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/ultraestrutura , Transfecção
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