共查询到20条相似文献，搜索用时 31 毫秒
1.
Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice 总被引：1，自引：0，他引：1
Clement AM Nguyen MD Roberts EA Garcia ML Boillée S Rule M McMahon AP Doucette W Siwek D Ferrante RJ Brown RH Julien JP Goldstein LS Cleveland DW 《Science (New York, N.Y.)》2003,302(5642):113-117
The most common inherited [correct] form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting adult motor neurons, is caused by dominant mutations in the ubiquitously expressed Cu-Zn superoxide dismutase (SOD1). In chimeric mice that are mixtures of normal and SOD1 mutant-expressing cells, toxicity to motor neurons is shown to require damage from mutant SOD1 acting within nonneuronal cells. Normal motor neurons in SOD1 mutant chimeras develop aspects of ALS pathology. Most important, nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons. 相似文献
2.
Neuronal generation of the leech swimming movement 总被引：5，自引：0，他引：5
G S Stent W B Kristan W O Friesen C A Ort M Poon R L Calabrese 《Science (New York, N.Y.)》1978,200(4348):1348-1357
The swimming movement of the leech is produced by an ensemble of bilaterally symmetric, rhythmically active pairs of motor neurons present in each segmental ganglion of the ventral nerve cord. These motor neurons innervate the longitudinal muscles in dorsal or ventral sectors of the segmental body wall. Their duty cycles are phase-locked in a manner such that the dorsal and ventral body wall sectors of any given segment undergo an antiphasic contractile rhythm and that the contractile rhythms of different segments form a rostrocaudal phase progression. This activity rhythm is imposed on the motor neurons by a central swim oscillator, of which four bilaterally symmetric pairs of interneurons present in each segmental ganglion appear to constitute the major component. These interneurons are linked intra- and intersegmentally via inhibitory connections to form a segmentally iterated and inter-segmentally concatenated cyclic neuronal network. The network appears to owe its oscillatory activity pattern to the mechanism of recurrent cyclic inhibition. 相似文献
3.
Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neuromuscular disease that is associated with the degeneration of spinal and brainstem motor neurons, leading to atrophy of limb, axial, and respiratory muscles. The cause of ALS is unknown, and there is no effective therapy. Neurotrophic factors are candidates for therapeutic evaluation in ALS. Although chronic delivery of molecules to the central nervous system has proven difficult, we recently discovered that adeno-associated virus can be retrogradely transported efficiently from muscle to motor neurons of the spinal cord. We report that insulin-like growth factor 1 prolongs life and delays disease progression, even when delivered at the time of overt disease symptoms. 相似文献
4.
Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils 总被引：1，自引：0，他引：1
beta-Amyloid plaques and neurofibrillary tangles (NFTs) are the defining neuropathological hallmarks of Alzheimer's disease, but their pathophysiological relation is unclear. Injection of beta-amyloid Abeta42 fibrils into the brains of P301L mutant tau transgenic mice caused fivefold increases in the numbers of NFTs in cell bodies within the amygdala from where neurons project to the injection sites. Gallyas silver impregnation identified NFTs that contained tau phosphorylated at serine 212/threonine 214 and serine 422. NFTs were composed of twisted filaments and occurred in 6-month-old mice as early as 18 days after Abeta42 injections. Our data support the hypothesis that Abeta42 fibrils can accelerate NFT formation in vivo. 相似文献
5.
6.
Fernandez-Gonzalez A La Spada AR Treadaway J Higdon JC Harris BS Sidman RL Morgan JI Zuo J 《Science (New York, N.Y.)》2002,295(5561):1904-1906
The classical recessive mouse mutant, Purkinje cell degeneration (pcd), exhibits adult-onset degeneration of cerebellar Purkinje neurons, retinal photoreceptors, olfactory bulb mitral neurons, and selected thalamic neurons, and has defective spermatogenesis. Here we identify Nna1 as the gene mutated in the original pcd and two additional pcd alleles (pcd2J and pcd3J). Nna1 encodes a putative nuclear protein containing a zinc carboxypeptidase domain initially identified by its induction in spinal motor neurons during axonal regeneration. The present study suggests an unexpected molecular link between neuronal degeneration and regeneration, and its results have potential implications for neurodegenerative diseases and male infertility. 相似文献
7.
Mallucci G Dickinson A Linehan J Klöhn PC Brandner S Collinge J 《Science (New York, N.Y.)》2003,302(5646):871-874
The mechanisms involved in prion neurotoxicity are unclear, and therapies preventing accumulation of PrPSc, the disease-associated form of prion protein (PrP), do not significantly prolong survival in mice with central nervous system prion infection. We found that depleting endogenous neuronal PrPc in mice with established neuroinvasive prion infection reversed early spongiform change and prevented neuronal loss and progression to clinical disease. This occurred despite the accumulation of extraneuronal PrPSc to levels seen in terminally ill wild-type animals. Thus, the propagation of nonneuronal PrPSc is not pathogenic, but arresting the continued conversion of PrPc to PrPSc within neurons during scrapie infection prevents prion neurotoxicity. 相似文献
8.
Miyake N Chilton J Psatha M Cheng L Andrews C Chan WM Law K Crosier M Lindsay S Cheung M Allen J Gutowski NJ Ellard S Young E Iannaccone A Appukuttan B Stout JT Christiansen S Ciccarelli ML Baldi A Campioni M Zenteno JC Davenport D Mariani LE Sahin M Guthrie S Engle EC 《Science (New York, N.Y.)》2008,321(5890):839-843
Duane's retraction syndrome (DRS) is a complex congenital eye movement disorder caused by aberrant innervation of the extraocular muscles by axons of brainstem motor neurons. Studying families with a variant form of the disorder (DURS2-DRS), we have identified causative heterozygous missense mutations in CHN1, a gene on chromosome 2q31 that encodes alpha2-chimaerin, a Rac guanosine triphosphatase-activating protein (RacGAP) signaling protein previously implicated in the pathfinding of corticospinal axons in mice. We found that these are gain-of-function mutations that increase alpha2-chimaerin RacGAP activity in vitro. Several of the mutations appeared to enhance alpha2-chimaerin translocation to the cell membrane or enhance its ability to self-associate. Expression of mutant alpha2-chimaerin constructs in chick embryos resulted in failure of oculomotor axons to innervate their target extraocular muscles. We conclude that alpha2-chimaerin has a critical developmental function in ocular motor axon pathfinding. 相似文献
9.
The histochemical reaction for phosphorylase is completely lost from anterior horn neurons rich in phosphorylase within 72 hours after proximal or distal axonal section. Using this new type of axonal reaction as a marking technique in the anterior horn of the seventh lumbar spinal cord segment of the cat, we demonstrated that (i) alpha motor neurons of slow twitch motor units, like those of fast twitch motor units, are rich in phosphorylase and poor in succinate dehydrogenase, and (ii) interneurons and Renshaw neurons are rich in succinate dehydrogenase and poor in phosphorylase. Gamma motor neurons, because of their small size, are considered to be rich in succinate dehydrogenase and poor in phosphorylase. Thus, anterior horn neurons capable of higher firing frequencies (Renshaw neurons, interneurons, and gamma motor neurons) are richer in mitochondrial oxidative enzyme activity as marked by succinate dehydrogenase. Those firing at lower frequencies (both types of alpha motor neurons) are richer in phosphorylase activity and glycogen content and, thus, apparently better equipped for anaerobic glycolysis. 相似文献
10.
Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons 总被引：3，自引：0，他引：3
Dimos JT Rodolfa KT Niakan KK Weisenthal LM Mitsumoto H Chung W Croft GF Saphier G Leibel R Goland R Wichterle H Henderson CE Eggan K 《Science (New York, N.Y.)》2008,321(5893):1218-1221
The generation of pluripotent stem cells from an individual patient would enable the large-scale production of the cell types affected by that patient's disease. These cells could in turn be used for disease modeling, drug discovery, and eventually autologous cell replacement therapies. Although recent studies have demonstrated the reprogramming of human fibroblasts to a pluripotent state, it remains unclear whether these induced pluripotent stem (iPS) cells can be produced directly from elderly patients with chronic disease. We have generated iPS cells from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis (ALS). These patient-specific iPS cells possess properties of embryonic stem cells and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS. 相似文献
11.
Expression and function of the segmentation gene fushi tarazu during Drosophila neurogenesis 总被引：33，自引：0，他引：33
Segmentation genes control cell identities during early pattern formation in Drosophila. One of these genes, fushi tarazu (ftz), is now shown also to control cell fate during neurogenesis. Early in development, ftz is expressed in a striped pattern at the blastoderm stage. Later, it is transiently expressed in a specific subset of neuronal precursor cells, neurons (such as aCC, pCC, RP1, and RP2), and glia in the developing central nervous system (CNS). The function of ftz in the CNS was determined by creating ftz mutant embryos that express ftz in the blastoderm stripes but not in the CNS. In the absence of ftz CNS expression, some neurons appear normal (for example, the aCC, pCC, and RP1), whereas the RP2 neuron extends its growth cone along an abnormal pathway, mimicking its sibling (RP1), suggesting a transformation in neuronal identity. 相似文献
12.
Electrical responses of insect central neurons: augmentation by nerve section or colchicine 总被引：3，自引：0，他引：3
Intracellular recording from the somata of central motor neurons in the cockroach Periplaneta americana normally shows little or no electrical response evoked by soma depolarization or by antidromic stimulation. Within 4 days after either cutting the axon or administration of colchicine, large action potentials can regularly be recorded from cell bodies of metathoracic motor neurons. Each experimental procedure evokes formation of a dense, perinuclear ribonucleic acid ring in the soma of neurons showing augmented electrical responses. 相似文献
13.
Olson L 《Science (New York, N.Y.)》2000,290(5492):721-724
The degeneration of dopamine neurons in the nigrostriatal pathway of the brain results in the debilitating motor deficits of Parkinson's disease. In a Perspective, Olson discusses a new study (Kordower et al.) demonstrating that injection of a lentiviral vector containing the gene encoding GDNF (a trophic factor for dopamine neurons) into the nigrostriatal pathway of monkeys with PD prevents neuronal loss and reverses some of the motor deficits of this disease. 相似文献
14.
Motor cortex output is capable of considerable reorganization, which involves modulation of excitability within the cortex. Does such reorganization also involve changes beyond the cortex, at the level of throughput from single motor cortex neurons to muscle activity? We examined such throughput during a paradigm that provided incentive for enhancing functional connectivity from motor cortex neurons to muscles. Short-latency throughput from a recorded neuron to muscle activity not present during some behavioral epochs often appeared during others. Such changes in throughput could not always be attributed to a higher neuron firing rate, to more ongoing muscle activity, or to neuronal synchronization, indicating that reorganization of motor cortex output may involve rapid changes in functional connectivity from single motor cortex neurons to alpha-motoneuron pools. 相似文献
15.
Identification and characterization of a neuron-specific nuclear antigen in Drosophila 总被引：7，自引：0，他引：7
An antigen found only in neuronal nuclei of Drosophila melanogaster is revealed by staining with a monoclonal antibody (Mab44C11). This antigen appears early in development, before neurons show any other signs of antigenic or morphologic differentiation, and persists throughout development. This nuclear staining permits reliable detection of neurons in developmental studies of wild-type and mutant flies. Protein immunoblot analyses and immune precipitation experiments show that the neuronal nuclear antigen is a 50-kilodalton polypeptide. 相似文献
16.
17.
18.
Luo J Kaplitt MG Fitzsimons HL Zuzga DS Liu Y Oshinsky ML During MJ 《Science (New York, N.Y.)》2002,298(5592):425-429
The motor abnormalities of Parkinson's disease (PD) are caused by alterations in basal ganglia network activity, including disinhibition of the subthalamic nucleus (STN), and excessive activity of the major output nuclei. Using adeno-associated viral vector-mediated somatic cell gene transfer, we expressed glutamic acid decarboxylase (GAD), the enzyme that catalyzes synthesis of the neurotransmitter GABA, in excitatory glutamatergic neurons of the STN in rats. The transduced neurons, when driven by electrical stimulation, produced mixed inhibitory responses associated with GABA release. This phenotypic shift resulted in strong neuroprotection of nigral dopamine neurons and rescue of the parkinsonian behavioral phenotype. This strategy suggests that there is plasticity between excitatory and inhibitory neurotransmission in the mammalian brain that could be exploited for therapeutic benefit. 相似文献
19.
In rhesus monkeys, corticospinal fibers have been found to terminate in motor, sensory, and internuncial cell groups. The present study reveals that the subcorticospinal fibers terminate primarily on internuncial neurons. Possible mechanisms involved in transmission of cortical and subcortical influences on motor and sensory cell groups are discussed. 相似文献
20.
Cell adhesion molecules 总被引：77，自引：0，他引：77
G M Edelman 《Science (New York, N.Y.)》1983,219(4584):450-457
It has been proposed that cell-cell recognition occurs by means of local cell surface modulation of a small number of proteins rather than by expression of large numbers of different cell surface markers. Several different cell adhesion molecules (CAM's) have now been found in a number of vertebrate species in different tissues such as liver and striated muscle and even in a single complex structure such as the brain, where different molecules specific for neurons and glia have been identified. The neuron-specific molecule is involved in early embryonic events but also mediates neurite fasciculation, neuromuscular interaction, and orderly layering of neural tissue. It undergoes local surface modulation with loss of sialic acid during development. A failure of this process is closely correlated with connectional disorders in the staggerer mutant of the mouse. The accumulated data on this and other CAM's favor modulation theories rather than strict chemoaffinity theories of cell-cell recognition. 相似文献