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Tristano Pancani Jeremiah T. Phelps James L. Searcy Michael W. Kilgore Kuey-Chu Chen Nada M. Porter Olivier Thibault 《Journal of neurochemistry》2009,109(6):1800-1811
Type 2 diabetes mellitus is a metabolic disorder characterized by hyperglycemia and is especially prevalent in the elderly. Because aging is a risk factor for type 2 diabetes mellitus, and insulin resistance may contribute to the pathogenesis of Alzheimer's disease (AD), anti-diabetic agents (thiazolidinediones-TZDs) are being studied for the treatment of cognitive decline associated with AD. These agents normalize insulin sensitivity in the periphery and can improve cognition and verbal memory in AD patients. Based on evidence that Ca2+ dysregulation is a pathogenic factor of brain aging/AD, we tested the hypothesis that TZDs could impact Ca2+ signaling/homeostasis in neurons. We assessed the effects of pioglitazone and rosiglitazone (TZDs) on two major sources of Ca2+ influx in primary hippocampal cultured neurons, voltage-gated Ca2+ channel (VGCC) and the NMDA receptor (NMDAR). VGCC- and NMDAR-mediated Ca2+ currents were recorded using patch-clamp techniques, and Ca2+ intracellular levels were monitored with Ca2+ imaging techniques. Rosiglitazone, but not pioglitazone reduced VGCC currents. In contrast, NMDAR-mediated currents were significantly reduced by pioglitazone but not rosiglitazone. These results show that TZDs modulate Ca2+ -dependent pathways in the brain and have different inhibitory profiles on two major Ca2+ sources, potentially conferring neuroprotection to an area of the brain that is particularly vulnerable to the effects of aging and/or AD. 相似文献
47.
Eric A. Pohlmeyer Emily R. Oby Eric J. Perreault Sara A. Solla Kevin L. Kilgore Robert F. Kirsch Lee E. Miller 《PloS one》2009,4(6)
Loss of hand use is considered by many spinal cord injury survivors to be the most devastating consequence of their injury. Functional electrical stimulation (FES) of forearm and hand muscles has been used to provide basic, voluntary hand grasp to hundreds of human patients. Current approaches typically grade pre-programmed patterns of muscle activation using simple control signals, such as those derived from residual movement or muscle activity. However, the use of such fixed stimulation patterns limits hand function to the few tasks programmed into the controller. In contrast, we are developing a system that uses neural signals recorded from a multi-electrode array implanted in the motor cortex; this system has the potential to provide independent control of multiple muscles over a broad range of functional tasks. Two monkeys were able to use this cortically controlled FES system to control the contraction of four forearm muscles despite temporary limb paralysis. The amount of wrist force the monkeys were able to produce in a one-dimensional force tracking task was significantly increased. Furthermore, the monkeys were able to control the magnitude and time course of the force with sufficient accuracy to track visually displayed force targets at speeds reduced by only one-third to one-half of normal. Although these results were achieved by controlling only four muscles, there is no fundamental reason why the same methods could not be scaled up to control a larger number of muscles. We believe these results provide an important proof of concept that brain-controlled FES prostheses could ultimately be of great benefit to paralyzed patients with injuries in the mid-cervical spinal cord. 相似文献
48.
Dona F. Boggs Delbert L. Kilgore Jr. 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1983,149(4):527-533
Summary The fractional concentration of CO2 within the occupied burrows of burrow-dwelling birds has been measured at 0.065 or higher while the fractional concentration of O2 can be 0.14 or lower. The ventilatory responses of the Burrowing Owl (Athene cunicularia) and a non-burrowing bird, the Bobwhite (Colinus virginianus), to the levels of hypercarbia, hypoxia and hypoxic hypercarbia likely encountered by this owl within its burrow were assessed. Ventilatory responses toFi
CO
2 of 0.01, 0.03, 0.05 and 0.07 at normoxia; toFi
CO
2 of 0.19, 0.17, 0.15 and 0.13 at normocarbia; and to combinedFi
CO
2 andFi
O
2 of 0.01:0.19, 0.03:0.17, 0.05:0.15 and 0.07:0.13 were measured by volumetric plethysmography. The Burrowing Owl exhibited a significantly attenuated ventilatory response to these levels of hypercarbia, hypoxia and hypoxic hypercarbia compared to the non-burrow-dwelling Bobwhite. A reduced ventilatory response to the hypoxic and hypercarbic stimuli has been previously observed in fossorial mammals, and is reported here for the first time in a burrow-dwelling bird. This reduced response is believed to represent an adaptation to burrow atmospheric conditions.Abbreviations
F
fractional concentration (of O2 and CO2)
-
f
respiratory frequency
-
V
T
tidal volume
-
V
D
dead space (tracheal volume) 相似文献
49.
When cells of Escherichia coli B growing in a glucose-synthetic medium were treated with mitomycin C, the effects produced by the antibiotic varied, depending on the concentration. When the concentration was reduced to less than 0.1 mug/ml, the action of the antibiotic was bacteriostatic; cell elongation resulted, but no effect on the synthesis of cellular macromolecules was apparent. At higher levels (more than 5 mug/ml), mitomycin C was highly bactericidal and inhibited deoxyribonucleic acid synthesis almost completely. The exposure of growing cells to a bactericidal level of mitomycin C resulted also in a delayed inhibition of the synthesis of ribonucleic acid (RNA) and protein. The capacity of the treated cells to synthesize beta-galactosidase inducibly in a medium free from a carbon source remained constant for the first 30 min and then was destroyed progressively with time. Prolonged incubation with the bactericidal level of mitomycin C caused a degradation of cellular nucleic acids, particularly RNA. The degraded nucleic acid components were eventually released into the medium. 相似文献
50.
Glynn Dennis Jr Cécile TJ Holweg Sarah K Kummerfeld David F Choy A Francesca Setiadi Jason A Hackney Peter M Haverty Houston Gilbert Wei Yu Lin Lauri Diehl S Fischer An Song David Musselman Micki Klearman Cem Gabay Arthur Kavanaugh Judith Endres David A Fox Flavius Martin Michael J Townsend 《Arthritis research & therapy》2014,16(2):R90