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Neurodegeneration changes in primary central nervous system neurons transfected with the Alzheimer-associated neuronal thread protein gene 总被引:6,自引:0,他引:6
The AD7c-NTP gene is over-expressed in brains with Alzheimer's disease (AD), and increased levels of the corresponding protein
are detectable in cortical neurons, brain tissue extracts, cerebrospinal fluid, and urine beginning early in the course of
AD neurodegeneration. In the present study, we utilized a novel method to transfect post-mitotic primary neuronal cell cultures,
and demonstrated that over-expression of the AD7c-NTP gene causes cell death and neuritic sprouting, two prominent abnormalities
associated with AD. These results provide further evidence that aberrantly increas-ed AD7c-NTP expression may have a role
in AD-type neurodegeneration. In addition, we demonstrate that primary post-mitotic neurons can be efficiently transfected
with conventional recombinant plasmid DNA to evaluate the effects of gene over-expression in relevant in vitro models.
Received 31 January 2001; received after revision 31 March 2001; accepted 4 April 2001 相似文献
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Pfrieger FW 《Cellular and molecular life sciences : CMLS》2003,60(6):1158-1171
Cholesterol is a multifaceted molecule. First, it serves as an essential membrane component, as a cofactor for signaling molecules and as a precursor for steroid hormones; second, its synthesis, intercellular transport and intracellular distribution present a logistic tour de force requiring hundreds of cellular components, and third, it plays a crucial role in major human diseases. Despite intense research on this molecule, its metabolism in the central nervous system and its role in neuronal development and function are not well understood. Here I summarize recent results and hypotheses about how neurons maintain their cholesterol level and how cholesterol influences the establishment and maintenance of synaptic connections. 相似文献
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Neurotrophins and neuronal differentiation in the central nervous system 总被引:10,自引:0,他引:10
McAllister AK 《Cellular and molecular life sciences : CMLS》2001,58(8):1054-1060
The central nervous system requires the proper formation of exquisitely precise circuits to function properly. These neuronal
circuits are assembled during development by the formation of synaptic connections between hundreds of thousands of differentiating
neurons. For these circuits to form correctly, neurons must elaborate precisely patterned axonal and dendritic arbors. Although
the cellular and molecular mechanisms that guide neuronal differentiation and formation of connections remain mostly unknown,
the neurotrophins have emerged recently as attractive candidates for regulating neuronal differentiation in the developing
brain. The experiments reviewed here provide strong support for a bifunctional role for the neurotrophins in axonal and dendritic
growth and are consistent with the exciting possibility that the neurotrophins might mediate activity-dependent synaptic plasticity. 相似文献
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Gavin C. Higgins Philip M. Beart Phillip Nagley 《Cellular and molecular life sciences : CMLS》2009,66(16):2773-2787
To characterize neuronal death, primary cortical neurons (C57/Black 6 J mice) were exposed to hydrogen peroxide (H2O2) and staurosporine. Both caused cell shrinkage, nuclear condensation, DNA fragmentation and loss of plasma membrane integrity.
Neither treatment induced caspase-7 activity, but caspase-3 was activated by staurosporine but not H2O2. Each treatment caused redistribution from mitochondria of both endonuclease G (Endo G) and cytochrome c. Neurons knocked down for Endo G expression using siRNA showed reduction in both nuclear condensation and DNA fragmentation
after treatment with H2O2, but not staurosporine. Endo G suppression protected cells against H2O2-induced cell death, while staurosporine-induced death was merely delayed. We conclude that staurosporine induces apoptosis
in these neurons, but severe oxidative stress leads to Endo G-dependent death, in the absence of caspase activation (programmed
cell death-type III). Therefore, oxidative stress triggers in neurons a form of necrosis that is a systematic cellular response
subject to molecular regulation.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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Lombardo MF Ciriolo MR Rotilio G Rossi L 《Cellular and molecular life sciences : CMLS》2003,60(8):1733-1743
SH-SY5Y neuroblastoma cells were cultured for up to three serial passages in the presence of the copper chelator triethylene tetramine (Trien). The copper-depleted neuroblastoma cell line obtained showed decreased activities of the copper enzymes Cu, Zn superoxide dismutase and cytochrome c oxidase with concomitant increases in reactive oxygen species. Mitochondrial antioxidants (Mn superoxide dismutase and Bcl-2) were up-regulated. Overexpression and activation of p53 were early responses, leading to an increase in p21. Eventually, copper-depleted cells detached from the monolayer and underwent apoptosis. Activation of up-stream caspase-9, but not caspase-8, suggested that apoptosis proceeds via a mitochondrial pathway, followed by caspase-3 activation. The addition of copper sulfate to the copper-depleted cells restored copper enzymes, normalized antioxidant levels and improved cell viability. We conclude that prolonged copper starvation in these replicating cells leads to mitochondrial damage and oxidative stress and ultimately, apoptosis.Received 24 April 2003; accepted 23 May 2003 相似文献
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Han X 《Cellular and molecular life sciences : CMLS》2004,61(15):1896-1906
The critical roles of apolipoprotein E (apoE) in regulating plasma lipid and lipoprotein levels have been
extensively studied for over 2 decades. However, an understanding of the roles of apoE in the central nervous
system (CNS) is less certain. This review will summarize the available experimental results on the role of apoE
in CNS lipid homeostasis with respect to its modulation of sulfatide trafficking, alteration of CNS cholesterol
homeostasis and apoE-induced changes in phospholipid molecular species in specialized subcellular membrane
fractions. The results indicate that apoE mediates sulfatide trafficking and metabolism in the CNS. Moreover,
although apoE does not affect the cholesterol mass content or the phospholipid mass levels and composition in the
CNS as a whole, apoE modulates cholesterol and phospholipid homeostasis in selective subcellular membrane
compartments. Through elucidating the roles of apoE in CNS lipid metabolism, new insights into overall functions
of apoE in neurobiology can be accrued ultimately, leading to an increased understanding of CNS lipid metabolism
and the identification of novel therapeutic targets for CNS diseases.Received 9 January 2004; received after revision 28 February 2004; accepted 10 March 2004 相似文献
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A. Menendez-Patterson J. A. Florez-Lozano B. Marin 《Cellular and molecular life sciences : CMLS》1978,34(2):190-192
Summary The results indicate significant increases of the oxidative metabolism in the oestrus of the ovaries, hypothalamus and the posterior cortex, while in the amygdala this increase occurs in the phase of diestrus. 相似文献
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Scavenger receptor family proteins: roles for atherosclerosis, host defence and disorders of the central nervous system 总被引:11,自引:1,他引:10
Y. Yamada T. Doi T. Hamakubo T. Kodama 《Cellular and molecular life sciences : CMLS》1998,54(7):628-640
In this review, we summarize the structure and function of the scavenger receptor family of proteins including class A (type I and II macrophage scavenger receptors, MARCO), class B (CD36, scavenger receptor class BI), mucinlike (CD68/macrosialin, dSR-CI) and endothelial (LOX-1) receptors. Two motifs have been identified as ligand-binding domains a charged collagen structure of type I and II receptors, and an immunodominant domain of CD36. These structures can recognize a wide range of negatively charged macromolecules, including oxidized low-density lipoproteins, damaged or apoptotic cells, and pathogenic microorganisms. After binding, these ligands can be either internalized by endocytosis or phagocytosis, or remain at the cell surface and mediate adhesion or lipid transfer through caveolae. Under physiological conditions, scavenger receptors serve to scavenge or clean up cellular debris and other related materials, and they play a role in host defence. In pathological states, they mediate the recruitment, activation and transformation of macrophages and other cells which may be related to the development of atherosclerosis and to disorders caused by the accumulation of denatured materials, such as Alzheimer's disease. Received 17 September 1997; received after revision 16 March 1998; accepted 17 March 1998 相似文献
11.
Central nervous system stem cells in the embryo and adult 总被引:19,自引:0,他引:19
J. Frisén C. B. Johansson C. Lothian U. Lendahl 《Cellular and molecular life sciences : CMLS》1998,54(9):935-945
The central nervous system is generated from neural stem cells during embryonic development. These cells are multipotent and generate neurons, astrocytes and oligodendrocytes. The last few years it has been found that there are populations of stem cells also in the adult mammalian brain and spinal cord. In this paper, we review the recent development in the field of embryonic and adult neural stem cells. Received 26 March 1998; received after revision 27 April 1998; accepted 27 April 1998 相似文献
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Chronic gestational exposure to ethanol impairs insulin-stimulated survival and mitochondrial function in cerebellar neurons 总被引:6,自引:1,他引:5
Chronic gestational exposure to ethanol has profound adverse effects on brain development. In this regard, studies using
in vitro models of ethanol exposure demonstrated impaired insulin signaling mechanisms associated with increased apoptosis
and reduced mitochondrial function in neuronal cells. To determine the relevance of these findings to fetal alcohol syndrome,
we examined mechanisms of insulin-stimulated neuronal survival and mitochondrial function using a rat model of chronic gestational
exposure to ethanol. In ethanol-exposed pups, the cerebellar hemispheres were hypoplastic and exhibited increased apoptosis.
Isolated cerebellar neurons were cultured to selectively evaluate insulin responsiveness. Gestational exposure to ethanol
inhibited insulin-stimulated neuronal viability, mitochondrial function, Calcein AM retention (membrane integrity), and GAPDH
expression, and increased dihydrorosamine fluorescence (oxidative stress) and pro-apoptosis gene expression (p53, Fas-receptor,
and Fas-ligand). In addition, neuronal cultures generated from ethanol-exposed pups had reduced levels of insulin-stimulated
Akt, GSK-3β, and BAD phosphorylation, and increased levels of non-phosphorylated (activated) GSK-3β and BAD protein expression.
The aggregate results suggest that insulin-stimulated central nervous system neuronal survival mechanisms are significantly
impaired by chronic gestational exposure to ethanol, and that the abnormalities in insulin signaling mechanisms persist in
the early postnatal period, which is critical for brain development.
Received 21 January 2002; received after revision 28 February 2002; accepted 25 March 2002 相似文献
13.
Nicotinic acetylcholine receptors (nAChRs) exist in many subtypes and are found in the peripheral and central nervous system
where they mediate or modulate synaptic transmission. We review how tyrosine phosphorylation and kinases regulate muscle and
neuronal nAChRs. Interestingly, although some of the same kinase players interact with the various receptor subtypes, the
functional consequences are different. While concerted action of MuSK, Abl- and Src-family kinases (SFKs) regulates the synaptic
distribution of nAChRs at the neuromuscular junction, SFKs activate heteromeric neuronal nAChRs in adrenal chromaffin cells,
thereby enhancing catecholamine secretion. In contrast, the activity of homomeric neuronal nAChRs, as found in the hippocampus,
is negatively regulated by tyrosine phosphorylation and SFKs. It appears that tyrosine kinases provide the means to regulate
all nAChRs; but the functional consequences, even those caused by the same kinase family, are specific for each receptor subtype
and location.
Received 21 February 2006; received after revision 24 July 2006; accepted 30 August 2006 相似文献
14.
P. E. Pilet 《Cellular and molecular life sciences : CMLS》1998,54(8):851-865
Several characteristics of the plant hormone abscisic acid (ABA) are critically discussed, more or less directly, in relation to the extension of root cells. A few topics have been selected some biochemical characteristics of ABA (chemical structure, metabolism), inhibiting-β complex, inhibiting regulators from root caps, endogenous ABA in growing roots (ABA gradients, microsurgical experiments, light effects), applied ABA on elongating roots, ABA and indol-3yl acetic acid (IAA) interactions (root growth, proton extrusion, hormone transport, auxin herbicides), ABA effect on the root cell cycle, ABA and drought cells of elongating roots [water deficit conditions, IAA and jasmonic acid (JA) as ‘stress hormones’ other than ABA, gene expression]. Received 28 January 1998; received after revision 20 April 1998; accepted 21 April 1998 相似文献