DOPAMINE D2 RECEPTOR MECHANISMS CONTRIBUTE TO AGE-RELATED COGNITIVE DECLINE - THE EFFECTS OF QUINPIROLE ON MEMORY AND MOTOR-PERFORMANCE IN MONKEYS

The D2 dopamine (DA) receptor agonist, quinpirole, was characterized in young adult monkeys, young reserpine-treated monkeys and aged monkeys to assess the contribution of DA to age-related loss of prefrontal cortical (PFC) cognitive function, Monkeys were tested on a delayed response memory task that depends on the PFC, and a fine motor task that taps the functions of the motor cortex, In young adult monkeys, low quinpirole doses impaired performance of the PFC and fine motor tasks, while higher doses improved memory performance and induced dyskinesias and ''hallucinatory-like'' behaviors. The pattern of the quinpirole response in reserpine-treated monkeys suggested that the impairments in delayed response and fine motor performance resulted from drug actions at D2 autoreceptors, while the improvement in delayed response performance, dyskinesias and ''hallucinatory-like'' behaviors resulted from actions at postsynaptic receptors. In aged monkeys, low doses of quinpirole continued to impair fine motor performance, but lost their ability to impair delayed response performance. The magnitude of cognitive improvement and the incidence of ''hallucinatory-like'' behaviors were also reduced in the aged animals, suggesting some loss of postsynaptic D2 receptor function, The pattern of results is consistent with the greater loss of DA from the PFC than from motor areas in aged monkey brain (Goldman-Rakic and Brown, 1981; Wenk et al., 1989), and indicates that DA depletion contributes significantly to age-related cognitive decline.

DOPAMINE D-1 RECEPTOR MECHANISMS IN THE COGNITIVE PERFORMANCE OF YOUNG-ADULT AND AGED MONKEYS

Dopamine (DA) D-1 receptor compounds were examined in monkeys for effects on the working memory functions of the prefrontal cortex and on the fine motor abilities of the primary motor cortex. The D-1 antagonist, SCH23390, the partial D-1 agonist, SKF38393, and the full D-1 agonist, dihydrexidine, were characterized in young control monkeys, and in aged monkeys with naturally occurring catecholamine depletion. In addition, SKF38393 was tested in young monkeys experimentally depleted of catecholamines with chronic reserpine treatment. Injections of SCH23390 significantly impaired the memory performance of young control monkeys, but did not impair aged monkeys with presumed catecholamine depletion. Conversely, the partial agonist, SKF38393, improved the depleted monkeys (aged or reserpine-treated) but did not improve young control animals. The full agonist, dihydrexidine, did improve memory performance in young control monkeys, as well as in a subset of aged monkeys. Consistent with D, receptor mechanisms, agonist-induced improvements were blocked by SCH23390. Drug effects on memory performance occurred independently of effects on fine motor performance. These results underscore the importance of DA D-1 mechanisms in cognitive function, and provide functional evidence of DA system degeneration in aged monkeys. Finally, high doses of D-1 agonists impaired memory performance in aged monkeys, suggesting that excessive D-1 stimulation may be deleterious to cognitive function.

通过语言任务和功能磁共振成像研究人类小脑功能

Since the 19th century, people have long believed that the function of cerebellum was restricted to fine motor control and modulation. In the past two decades, however, more and more studies challenged this traditional view. While the neuroanatomy of the cerebellum from cellular to system level has been well documented, the functions of this neural organ remain poorly understood. This study, including three experiments, attempted to further the understanding of cerebellar functions from different viewpoints. Experiment One used the parametric design to control motor effects. The activation in cerebellum was found to be associated with the difficulty levels of a semantic discrimination task, suggesting the involvement of the cerebellum in higher level of language functions. Moreover, activation of the right posterior cerebellum was found to co-vary with that of the frontal cortex. Experiment Two adopted the cue-go paradigm and event-related design to exclude the effects of phonological and semantic factors in a mental writing task. The results showed that bilateral anterior cerebellum and cerebral motor regions were significantly activated during the task and the hemodynamic response of the cerebellum was similar to those of the cerebral motor cortex. These results suggest that the cerebellum participates in motor imagination during orthographic output. Experiment Three investigated the learning process of a verb generation task. While both lateral and vermis cerebellum were found to be activation in the task, each was correlated a separate set of frontal regions. More importantly, activations both in the cerebellum and frontal cortex decreased with the repetition of the task. These results indicate that the cerebellum and frontal cortex is jointly engaged in some functions; each serves as a part of a single functional system. Taken these findings together, the following conclusions can be drawn: 1.The cerebellum is not only involved in functions related to speech or articulation, but also participates in the higher cognitive functions of language. 2.The cerebellum participates in various functions by supporting the corresponding regions in cerebral cortex, but not directly executes the functions as an independent module. 3.The anterior part of cerebellum is related to motor functions, whereas the posterior part is involved in cognitive functions. 4.While the motor functions rely on the engagement of both sides of the cerebellar hemispheres, the higher cognitive functions mainly depend on the right cerebellum.

Dust-Cloud Structures behind a Shock Wave Moving Over a Deposited Layer of Fine Particles

The present paper investigates dispersed-phase flow structures of a dust cloud induced by a normal shock wave moving at a constant speed over a flat surface deposited with fine particles. In the shock-fitted coordinates, the general equations of dusty-gas

Earthquake Stability Analysis about Fine Grinded Tailings Dams

Based on the broken characteristics about earthquake to tailings dams, the earthquake stability analysis methods for tailings dams are introduced. Taking fine tailings dam in Longdu Tailings Pool as an example, the stability of the dam with various situations while earthquake with seven magnitude takes place there. The results can be used by Longdu Mine for tailings pool safety management.

Dynamics Of Fine Particles In Liquid-Solid Fluidized Beds

On the basis of the Local Equilibrium Model (LEM), fine particles with large Richardson-Zaki exponent n show, under certain conditions during bed expansion and collapse, different dynamic behavior from particles with small n. For an expansion process there may be a concentration discontinuity propagating upward from the distributor, and, on the contrary, for a collapse process there may be a progressively broadening and upward-propagating continuous transition zone instead of discontinuity. The predictions of the bed height variation and the discontinuity trace have been validated experimentally. (c) 2007 Chinese Society of Particuology and Institute of Process Engineering, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Novel experimental phenomena of fine-particle fluidized beds

The dynamic response of bed height and concentration waves in liquid-solid fluidized beds to a step change in the fluidization velocity is considered. We experimentally study the liquid-solid fluidized beds, spherical beadings, with sizes ranging from 230 to 270 mesh and the inner diameter of columns made from glass is 2.4 mm. Experimental results find that under certain conditions, fine particles with large Richardson-Zaki exponent n display different dynamic behavior from usual particles with smaller n during expansion and collapse of the fluidized state. (c) 2007 Elsevier Inc. All rights reserved.

A new model for the floating potential of fine particles in plasma

In the plasma processing of ultrafine particles of material, the heat transfer and force are considerably affected by particle charging. In this communication a new model, including thermal electron emission and incorporating the effect of electric field near the particle surface, is developed for metallic spherical particles under the condition of a thin plasma sheath. Based on this model, the particle floating potential, and thus the heat transfer and force, can be detemined more accurately and more realistically than previously.