共查询到20条相似文献,搜索用时 46 毫秒
1.
Background
Amyotrophic lateral sclerosis (ALS) is an age-dependent neurodegenerative disease that causes motor neuron degeneration, paralysis and death. Mutations in Cu, Zn superoxide dismutase (SOD1) are one cause for the familial form of this disease. Transgenic mice expressing mutant SOD1 develop age-dependent motor neuron degeneration, skeletal muscle weakness, paralysis and death similar to humans. The mechanism whereby mutant SOD1 induces motor neuron degeneration is not understood but widespread mitochondrial vacuolation has been observed during early phases of motor neuron degeneration. How this vacuolation develops is not clear, but could involve autophagic vacuolation, mitochondrial permeability transition (MPT) or uncharacterized mechanisms. To determine which of these possibilities are true, we examined the vacuolar patterns in detail in transgenic mice expressing mutant SOD1G93A. 相似文献2.
Ralf Palmisano Panagiota Golfi Peter Heimann Christopher Shaw Claire Troakes Thomas Schmitt-John Jörg W Bartsch 《BMC neuroscience》2011,12(1):24
Background
The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown but hypotheses about disease mechanisms include oxidative stress, defective axonal transport, mitochondrial dysfunction and disrupted RNA processing. Whereas familial ALS is well represented by transgenic mutant SOD1 mouse models, the mouse mutant wobbler (WR) develops progressive motor neuron degeneration due to a point mutation in the Vps54 gene, and provides an animal model for sporadic ALS. VPS54 protein as a component of a protein complex is involved in vesicular Golgi trafficking; impaired vesicle trafficking might also be mechanistic in the pathogenesis of human ALS. 相似文献3.
Bogdan?Beirowski Robert?Adalbert Diana?Wagner Daniela?S?Grumme Klaus?Addicks Richard?R?Ribchester Michael?P?Coleman
Background
The progressive nature of Wallerian degeneration has long been controversial. Conflicting reports that distal stumps of injured axons degenerate anterogradely, retrogradely, or simultaneously are based on statistical observations at discontinuous locations within the nerve, without observing any single axon at two distant points. As axon degeneration is asynchronous, there are clear advantages to longitudinal studies of individual degenerating axons. We recently validated the study of Wallerian degeneration using yellow fluorescent protein (YFP) in a small, representative population of axons, which greatly improves longitudinal imaging. Here, we apply this method to study the progressive nature of Wallerian degeneration in both wild-type and slow Wallerian degeneration (WldS) mutant mice. 相似文献4.
Chia-Yen Wu Dosh Whye Lisa Glazewski Leila Choe Douglas Kerr Kelvin H Lee Robert W Mason Wenlan Wang 《BMC neuroscience》2011,12(1):25
Background
Deletion or mutation(s) of the survival motor neuron 1 (SMN1) gene causes spinal muscular atrophy (SMA), a neuromuscular disease characterized by spinal motor neuron death and muscle paralysis. Complete loss of the SMN protein is embryonically lethal, yet reduced levels of this protein result in selective death of motor neurons. Why motor neurons are specifically targeted by SMN deficiency remains to be determined. In this study, embryonic stem (ES) cells derived from a severe SMA mouse model were differentiated into motor neurons in vitro by addition of retinoic acid and sonic hedgehog agonist. Proteomic and western blot analyses were used to probe protein expression alterations in this cell-culture model of SMA that could be relevant to the disease. 相似文献5.
Background
The infantile form of neuronal ceroid lipofuscinosis (also known as infantile Batten disease) is caused by hereditary deficiency of a lysosomal enzyme, palmitoyl-protein thioesterase-1 (PPT1), and is characterized by severe cortical degeneration with blindness and cognitive and motor dysfunction. The PPT1-deficient knockout mouse recapitulates the key features of the disorder, including seizures and death by 7–9 months of age. In the current study, we compared gene expression profiles of whole brain from PPT1 knockout and normal mice at 3, 5 and 8 months of age to identify temporal changes in molecular pathways implicated in disease pathogenesis. 相似文献6.
7.
Background
Lurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks. Parallel to this degeneration, GABAergic synapses in the deep cerebellar nuclei (DCN), the major recipient of the inhibitory PC projection, increase synaptic conductance. Here, we further investigated this phenomenon, using real-time RT-PCR to assess GABAA receptor subunit gene expression during PC degeneration. 相似文献8.
Background
Notch signaling pathways are conserved across species and traditionally have been implicated in cell fate determination during embryonic development. Notch signaling components are also expressed postdevelopmentally in the brains of adult mice and Drosophila. Recent studies suggest that Notch signaling may play a role in the physiological, rather than developmental, regulation of neurons. Here, we investigate a new non-developmental role for Caenorhabditis elegans lin-12 Notch signaling in neurons regulating the spontaneous reversal rate during locomotion. 相似文献9.
Julia Lindberg Peter Saetre Seiji Nishino Emmanuel Mignot Elena Jazin 《BMC neuroscience》2007,8(1):34
Background
Narcolepsy causes dramatic behavioral alterations in both humans and dogs, with excessive sleepiness and cataplexy triggered by emotional stimuli. Deficiencies in the hypocretin system are well established as the origin of the condition; both from studies in humans who lack the hypocretin ligand (HCRT) and in dogs with a mutation in hypocretin receptor 2 (HCRTR2). However, little is known about molecular alterations downstream of the hypocretin signals. 相似文献10.
Cassandra L Schlamp Yan Li Joel A Dietz Katherine T Janssen Robert W Nickells 《BMC neuroscience》2006,7(1):66-14
Background
Glaucoma is a chronic neurodegenerative disease of the retina, characterized by the degeneration of axons in the optic nerve and retinal ganglion cell apoptosis. DBA/2J inbred mice develop chronic hereditary glaucoma and are an important model system to study the molecular mechanisms underlying this disease and novel therapeutic interventions designed to attenuate the loss of retinal ganglion cells. Although the genetics of this disease in these mice are well characterized, the etiology of its progression, particularly with respect to retinal degeneration, is not. We have used two separate labeling techniques, post-mortem DiI labeling of axons and ganglion cell-specific expression of the βGeo reporter gene, to evaluate the time course of optic nerve degeneration and ganglion cell loss, respectively, in aging mice. 相似文献11.
12.
Background
Parkinson's disease, a prevalent neurodegenerative disease, is characterized by the reduction of dopaminergic neurons resulting in the loss of motor control, resting tremor, the formation of neuronal inclusions and ultimately premature death. Two inherited forms of PD have been linked to mutations in the α-synuclein and parkin genes. The parkin protein functions as an ubiquitin ligase targeting specific proteins for degradation. Expression of human α-synuclein in Drosophila neurons recapitulates the loss of motor control, the development of neuronal inclusions, degeneration of dopaminergic neurons and the ommatidial array to provide an excellent genetic model of PD.Results
To investigate the role of parkin, we have generated transgenic Drosophila that conditionally express parkin under the control of the yeast UAS enhancer. While expression of parkin has little consequence, co-expression of parkin with α-synuclein in the dopaminergic neurons suppresses the α-synuclein-induced premature loss of climbing ability. In addition directed expression of parkin in the eye counteracts the α-synuclein-induced degeneration of the ommatidial array. These results show that parkin suppresses the PD-like symptoms observed in the α-synuclein-dependent Drosophila model of PD.Conclusion
The highly conserved parkin E3 ubiquitin ligase can suppress the damaging effects of human α-synuclein. These results are consistent with a role for parkin in targeting α-synuclein to the proteasome. If this relationship is conserved in humans, this suggests that up-regulation of parkin should suppress α-synucleinopathic PD. The development of therapies that regulate parkin activity may be crucial in the treatment of PD.13.
Susanne Hoffmann Uwe Firzlaff Susanne Radtke-Schuller Britta Schwellnus Gerd Schuller 《BMC neuroscience》2008,9(1):65
Background
The mammalian auditory cortex can be subdivided into various fields characterized by neurophysiological and neuroarchitectural properties and by connections with different nuclei of the thalamus. Besides the primary auditory cortex, echolocating bats have cortical fields for the processing of temporal and spectral features of the echolocation pulses. This paper reports on location, neuroarchitecture and basic functional organization of the auditory cortex of the microchiropteran bat Phyllostomus discolor (family: Phyllostomidae). 相似文献14.
Tiziana Sacco Enrica Boda Eriola Hoxha Riccardo Pizzo Claudia Cagnoli Alfredo Brusco Filippo Tempia 《BMC neuroscience》2010,11(1):55
Background
The m-AAA (ATPases Associated with a variety of cellular Activities) is an evolutionary conserved metalloprotease complex located in the internal mitochondrial membrane. In the mouse, it is a hetero-oligomer variably formed by the Spg7, Afg3l1, and Afg3l2 encoded proteins, or a homo-oligomer formed by either Afg3l1 or Afg3l2. In humans, AFG3L2 and SPG7 genes are conserved, whereas AFG3L1 became a pseudogene. Both AFG3L2 and SPG7 are involved in a neurodegenerative disease, namely the autosomal dominant spinocerebellar ataxia SCA28 and a recessive form of spastic paraplegia, respectively. 相似文献15.
16.
Richard T Libby Gareth R Howell Iok-Hou Pang Olga V Savinova Adrienne K Mehalow Joseph W Barter Richard S Smith Abbot F Clark Simon WM John 《BMC neuroscience》2007,8(1):108
Background
Nitric oxide synthase 2 (NOS2) contributes to neural death in some settings, but its role in glaucoma remains controversial. NOS2 is implicated in retinal ganglion cell degeneration in a rat glaucoma model in which intraocular pressure (IOP) is experimentally elevated by blood vessel cauterization, but not in a rat glaucoma model where IOP was elevated by injection of hypertonic saline. To test the importance of NOS2 for an inherited glaucoma, in this study we both genetically and pharmacologically decreased NOS2 activity in the DBA/2J mouse glaucoma model. 相似文献17.
Background
The infantile onset form of Neuronal Ceroid Lipofuscinoses (INCL) is the earliest and most severe form of NCL, with neurological symptoms that reflect massive neurodegeneration in the CNS and retina. INCL is due to recessively inherited mutations at the CLN1 locus. This locus encodes the evolutionarily conserved enzyme palmitoyl-protein thioesterase 1 (PPT1), indicating an essential role for protein palmitoylation in normal neuronal function. 相似文献18.
Background
Rag1 (Recombination activation gene-1) mediates genomic rearrangement and is essential for adaptive immunity in vertebrates. This gene is also expressed in the olfactory epithelium, but its function there is unknown. 相似文献19.
Eric?Schmidlin Thierry?Wannier Jocelyne?Bloch Abderraouf?Belhaj-Saif Alexander?F?Wyss Eric?M?Rouiller
Background
After sub-total hemi-section of cervical cord at level C7/C8 in monkeys, the ipsilesional hand exhibited a paralysis for a couple of weeks, followed by incomplete recovery of manual dexterity, reaching a plateau after 40–50 days. Recently, we demonstrated that the level of the plateau was related to the size of the lesion and that progressive plastic changes of the motor map in the contralesional motor cortex, particularly the hand representation, took place following a comparable time course. The goal of the present study was to assess, in three macaque monkeys, whether the hand representation in the ipsilesional primary motor cortex (M1) was also affected by the cervical hemi-section. 相似文献20.
Paolo Bigini Fabrizio Gardoni Sara Barbera Alfredo Cagnotto Elena Fumagalli Annalisa Longhi Massimiliano M Corsi Monica Di Luca Tiziana Mennini 《BMC neuroscience》2006,7(1):71