1,721,035 research outputs found
Lipopolysaccharide-stimulated cortical microglia elaborate soluble factors which inhibit in vitro neurogenesis of adult neural stem/progenitor cells.
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Runx transcription factors: Lineage-specific regulators of neuronal precursor cell proliferation and post-mitotic neuron subtype development.
No full textRunt-related (RUNX) genes encode evolutionarily conserved transcription factors that play essential roles during development and adult tissue homeostasis. RUNX proteins regulate the transition from proliferation to differentiation in a variety of cell lineages. Moreover, they control the diversification of distinct cellular phenotypes in numerous tissues. Alterations of RUNX functions are associated with several cancers and other human pathologies, underscoring the vital roles of these transcription factors in adult organs. Insights into the functions and regulations of mammalian RUNX proteins have been provided mostly by studies of RUNX involvement in mechanisms of hematopoietic and skeletal development and disease. A growing number of recent investigations are revealing new functions for RUNX family members during the development of the mammalian nervous system. This review will discuss recent progress in the study of RUNX protein involvement in mammalian neural development, with emphasis on the differentiation of olfactory, sensory, and motor neuron lineages
Isolation and culture of neural progenitor cells from rat postnatal cerebellum.
No full textThe mammalian brain contains undifferentiated, mitotically active, and multipotent neural stem/progenitor cells that in vivo contribute new neurons and glia to specific areas of the mature brain. When isolated under the appropriate conditions, these cells maintain in vitro the ability to proliferate and differentiate into cells that express neuronal and glial markers. Neural stem/progenitor cells have been identified and isolated from many regions of the embryonic, postnatal, and adult central nervous system, including cerebellum. This chapter details techniques to isolate and culture neural progenitor cells from rat postnatal cerebellum, which can be used as an in vitro model to study the molecular mechanisms underlying proliferation and differentiation into mature neural cells induced by various stimuli including pharmacological agents
Cerebellar granular cell cultures as an in vitro model for antidepressant drug-induced neurogenesis
No full textBoth preclinical and clinical evidence suggested that antidepressant drugs upregulate hippocampal cell proliferation and neurogenesis. In addition, direct evidence was recently published that hippocampal de novo cell proliferation is necessary for antidepressant action. Within this frame, we used primary cultures of rat cerebellar granule cells (CGC) as an in vitro model of central nervous system (CNS) to investigate whether a neurogenic response could be elicited also in the cerebellum, upon chronic treatment with selective serotonin reuptake inhibitors (SSRIs). Furthermore, we assayed the presence of neural precursor cells in CGC, possibly responsive to proliferation and differentiation stimuli. We found that 1 microM fluoxetine increased cell proliferation, as assayed by [3H]-thymidine incorporation. CGC immunocytochemical analysis with neural cell-specific markers revealed the presence of granule neurons, glial cells, and a cell component that we named "round cells." Because only round cells displayed proliferation ability, as revealed by 5-bromo-2'-deoxyuridine (BrdU) labeling, they were further characterized. For this purpose, round cells were isolated and expanded by culturing in a serum-free medium, containing basic fibroblast growth factor (bFGF), before immunocytochemical analysis. We found that round cells were not immunoreactive for glial, neuronal, and oligodendrocyte markers, whereas they were immunoreactive for several immature neuronal markers. Accordingly, round cells could be induced to differentiate into astrocytes, neurons, and oligodendrocytes, either by withdrawing the mitogen bFGF or by exposing them to fluoxetine. These findings suggest that round cells in CGC possess the features and potentials of neural precursors, able to differentiate in mature neural cells upon a pharmacological simulum
Corrigendum: An Inflammation-Centric View of Neurological Disease: Beyond the Neuron
Full text linkIn the original article, there was a mistake in the legend for Figure 1 as published. We neglected to include the citation for the figure from which our figure was adapted and modified. The correct figure legend appears below. Figure 1. Microglia, like Janus, the two-faced Roman god of beginnings and transitions, display two sides—physiological as well as pathological. While microglial cell activation participates in surveillance that functions to maintain homeostasis and promote synaptic maturation, prolonged exposure to pathogen activators or in settings of systemic inflammation, asmay occur in conditions such as diabetes or obesity, can culminate in a state of chronic, non-resolving neuroinflammation. Ultimately, these responses will provoke functional and structural changes and neuronal cell death (neurodegeneration). [Adapted and modified from Heneka et al. (2015). Neuroinflammation in Alzheimer’s disease (Figure 1)]. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated
Protective effect of TAT-PARKIN on neuronal cells.
No full textParkinson’s disease is characterized by a progressive and selective loss of dopamine neurons in the substantia nigra pars compacta and decreased levels of striatal dopamine. Cytoplasmic inclusions (Lewy bodies) containing mainly aggregated alpha-synuclein (alpha-syn) and parkin are found in the surviving nigral dopaminergic neurons. Although largely sporadic, early-onset cases of Parkinson’s disease are associated with genetic mutations, including two missense mutations (alpha-synA53T and alpha-synA30P) in the alpha-syn gene. Recent studies suggest a protective role for parkin in dopaminergic neuron survival. Here we investigated a possible neuroprotective effect of parkin against alpha-synA30P-induced neurodegeneration, using rat pheochromocytoma PC12 cells. For this purpose, we have used a protein transduction domain derived from the human immunodeficiency TAT protein to engineer TAT-alpha-synA30P (Recchia et al. FASEB J. 2008) and TAT-parkin fusion proteins, to facilitate diffusion across the plasma membrane. Both TAT-parkin and TAT-alpha-synA30P were toxic to naive PC12 cells at concentrations above 100 uM. Incubation of PC12 cells with the dopaminergic neurotoxin 6-OHDA (5-300 uM) decreased cell viability in a time/concentration-dependent manner (40% at 0 hours, 70% at 6 hours). When PC12 cells were pre-incubated with 100 uM TAT-parkin for 24 hours, followed by challenge with 60 uM 6-OHDA, a neuroprotective effect was seen at time 0 only. However, when PC12 cells were pre-incubated with 100 uM TAT-parkin for 24 hours before treatment with 60 uM 6-OHDA for 2 hours, and then incubated a second time for 2-6 hours with 100 uM TAT-parkin, survival improved to 80% at all times, instead of 50% when treated only with 60 uM 6-OHDA. Our results show the utility of protein transduction domain technology in the study of neurodegenerative disease. The TAT-proteins described here represent useful tools for exploring the role of oxidative stress response and neuronal maintenance in Parkinson’s disease. This may lead to novel approaches in developing parkin as a therapeutic target for Parkinson’s disease, based on endogenous neuroprotective mechanisms
Identification in rat cerebellar granule cell cultures of neural precursors able to proliferate and differentiate in response to chronic treatment with selective serotonin reuptake inhibitors.
No full textPhosphatidylserine and Curcumin Act Synergistically to Down-Regulate Release of Interleukin-1β from Lipopolysaccharide-Stimulated Cortical Primary Microglial Cells.
No full textMicroglia, the brain's resident macrophages, contribute to immune surveillance and the response to disease and injury. These immune cells play a dual role in the nervous system, having both neurotoxic and neuroprotective effects. Activation of microglia results in the production of inflammatory molecules and neurotoxic factors that often cause or contribute to neurodegenerative diseases. Inhibition of neurotoxic microglia activation and consequent inflammatory processes may represent an important therapeutic target. Phosphatidylserine (PS), an aminophospholipid of plasma membranes, and curcumin, the yellow pigment isolated from the rhizome of the turmeric plant, have both been reported to suppress microglial activation by reducing pro-inflammatory mediator production and release. In this study we analyzed the effects of PS, curcumin, and their association on microglial activation induced by the bacterial toxin lipopolysaccharide. Primary rat cortical microglial cells were treated with increasing concentrations of PS-liposomes and curcumin, alone or in combination, and their effects on pro-inflammatory cytokine release from unstimulated and lipopolysaccharide-stimulated microglia were evaluated by enzyme-linked immunosorbent assay. Isobolographic analysis was performed to investigate the effect of PS-liposomes and curcumin combination. PS and curcumin inhibited the release of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α induced by lipopolysaccharide. Furthermore, PS and curcumin in combination exerted a synergistic effect in down-regulating IL-1β release. These results suggest that the association of PS with curcumin could be of potential therapeutic utility against diseases associated with microglial activation
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