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21.
Gene Expression Profiling Within the Developing Neural Tube 总被引:4,自引:0,他引:4
The developing mammalian nervous system is subject to devastating congenital malformations with clinical significance that extends into the billions of health care dollars annually worldwide. Neural tube defects (NTDs) are among the most common of all human congenital defects, yet their etiology remains poorly understood. This is largely due to the complexity of the genetic factors regulating the intricate events involved in neurulation. Using mouse model systems and the application of modern molecular biological technologies, we have recently gained a greater appreciation for the factors that not only regulate normal neural tube closure (NTC), but those genetic factors that predispose an embryo to significant birth defects such as anencephaly or spina bifida. We have selected prominent murine mutants, both spontaneous and genetically modified, as well as the use of teratogenic agents, to examine the impact of altering the normal pattern of gene expression in the developing neural tube. 相似文献
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To explore non-synaptic mechanisms in paroxysmal discharges, we used a computer model of a simplified hippocampal pyramidal
cell, surrounded by interstitial space and a “glial-endothelial” buffer system. Ion channels for Na+, K+, Ca2+ and Cl−
, ion antiport 3Na/Ca, and “active” ion pumps were represented in the neuron membrane. The glia had “leak” conductances and
an ion pump. Fluxes, concentration changes and cell swelling were computed. The neuron was stimulated by injecting current.
Afterdischarge (AD) followed stimulation if depolarization due to rising interstitial K+ concentration ([K+]o) activated persistent Na+ current (I
Na,P). AD was either simple or self-regenerating; either regular (tonic) or burst-type (clonic); and always self-limiting. Self-regenerating
AD required sufficient I
Na,P to ensure re-excitation. Burst firing depended on activation of dendritic Ca2+ currents and Ca-dependent K+ current. Varying glial buffer function influenced [K+]o accumulation and afterdischarge duration. Variations in Na+ and K+ currents influenced the threshold and the duration of AD. The data show that high [K+]o and intrinsic membrane currents can produce the feedback of self-regenerating afterdischarges without synaptic input. The
simulated discharge resembles neuron behavior during paroxysmal firing in living brain tissue.
Action Editor: David Terman 相似文献
23.
M. Van Der Stelt W. B. Veldhuis M. W. Wadman G. Van Zadelhoff F. Fezza G. A. Veldink J. F. G. Vliegenthart P. R. Br K. Nicolay V. Di Marzo 《Journal of neurochemistry》2003,85(Z2):6-6
The endocannabinoid anandamide (AEA) and some of its oxidative metabolites are putative ligands for the vanilloid receptor (VR1). AEA affords protection against excitotoxicity induced in vivo by ouabain, a Na+/K+‐ATPase inhibitor. This effect is only partly dependent of the cannabinoid CB1 receptor. Here, we assessed whether VR1 is involved in neuroprotection by AEA and arvanil, which is a hydrolysis‐stable ligand for both VR1 and CB1. Using magnetic resonance imaging we show that: (i) modulation of VR1, by the agonists arvanil and capsaicin and the antagonist capsazepine, leads to neuroprotective effects in the late but not acute phase after i.c. ouabain‐injection; (ii) arvanil is a potent neuroprotectant, acting at both CB1 and VR1; and (iii) the neuroprotective effects of AEA are mediated by CB1 but not by lipoxygenase metabolites or VR1. 相似文献
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As described by others, an extracellular calcium-sensitive non-selective cation channel ([Ca2+]o-sensitive NSCC) of central neurons opens when extracellular calcium level decreases. An other non-selective current is activated
by rising intracellular calcium ([Ca2+]
i
). The [Ca2+]o-sensitive NSCC is not dependent on voltage and while it is permeable by monovalent cations, it is blocked by divalent cations.
We tested the hypothesis that activation of this channel can promote seizures and spreading depression (SD). We used a computer
model of a neuron surrounded by interstitial space and enveloped in a glia-endothelial “buffer” system. Na+, K+, Ca2+ and Cl− concentrations, ion fluxes and osmotically driven volume changes were computed. Conventional ion channels and the NSCC were
incorporated in the neuron membrane. Activation of NSCC conductance caused the appearance of paroxysmal afterdischarges (ADs)
at parameter settings that did not produce AD in the absence of NSCC. The duration of the AD depended on the amplitude of
the NSCC. Similarly, NSCC also enabled the generation of SD. We conclude that NSCC can contribute to the generation of epileptiform
events and to spreading depression. 相似文献
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The predatory mite Phytoseiulus persimilis locates its prey, the two-spotted spider mite, by means of herbivore-induced plant volatiles. The olfactory response to this
quantitatively and qualitatively variable source of information is particularly well documented. The mites perform this task
with a peripheral olfactory system that consists of just five putative olfactory sensilla that reside in a dorsal field at
the tip of their first pair of legs. The receptor cells innervate a glomerular olfactory lobe just ventral of the first pedal
ganglion. We have made a 3D reconstruction of the caudal half of the olfactory lobe in adult females. The glomerular organization
as well as the glomerular innervation appears conserved across different individuals. The adult females have, by approximation,
a 1:1 ratio of olfactory receptor cells to olfactory glomeruli. 相似文献
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