摘要:

WE demonstrate the use of magnetic resonance imaging (MRI) for detection of neurotransmitter stimulation using the dopamine transporter ligands amphetamine and CFT (2β-carbomethoxy-3β-(4-fluorophenyl)tropane) as pharmacological challenges. We demonstrate that the unilateral loss of a hemodynamic response to either amphetamine or CFT challenge by unilateral 6-hydroxydopamine lesioning is restored by transplantation of fetal dopamine neurons in the striatum. The time course for the hemodynamic changes parallels the time courses for dopamine release, measured by prior microdialysis studies, and also for the rotational behavior in the unilaterally lesioned animals. Transplantation of the fetal cells results in hemodynamic time courses after CFT or amphetamine challenges at the graft site that are identical to those induced both before transplantation and on the intact contralateral side. The transplantation also results in complete behavioral recovery. The spatial extent of the dopaminergic recovery in the lesioned striatum is the same when measured using either PET of tracer levels of [11C]CFT binding or MRI. These results show great promise for the application of pharmacological MRI for application to studies of dopamine cell loss and potential recovery in Parkinson's disease.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

GENE therapy has developed as a promising approach for therapy in a broad variety of conditions. Viral vectors have been developed that may replace a defective gene, prevent expression of a mutant gene, or deliver a protective gene and thereby delay cellular loss. Using adeno-associated virus containing green fluorescent protein (AAV-GFP) we were able to specifically transduce cells located in the inner retina and induce over-expression of GFP in adult rat retinae. The delivery and expression of GFP had no influence themselves on retinal ganglion cell survival. Administration of the reporter vector AAV-GFP provided retinal ganglion cells with slight but significant protection from intravitreal NMDA. This was a locally mediated phenomenon; greater protection was seen in regions with more transduced cells. Any evaluation of the efficacy of a putative viral vector should consider the possible protective or toxic effect of the native virus.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

WE have recently reported that freeze-dried alginate gel, which was developed in our laboratory, enhanced peripheral nerve regeneration. The purpose of this study was to examine whether alginate gel is capable of promoting nerve regeneration in the severed spinal cord of adult mammals. Using Wistar rats at 30 days of age (P30), the T9–T10 spinal cord was totally resected and alginate gel was implanted across the gap. Forty-five days after surgery myelinated and unmyelinated axons regenerated throughout the gap with remaining alginate gel. The elongated axons established electrophysiologically functional projections across the gap. In conclusion, freeze-dried alginate gel could be a promising material as an artificial nerve guide for repair of injured central nervous system.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

THE time course and extent of attentional shifts associated with compensatory balancing reactions were explored using a novel dual-task paradigm. Seated subjects performed a continuous visuomotor tracking task with the hand while the feet simultaneously balanced an inverted pendulum. The pendulum was randomly perturbed, evoking compensatory balance reactions. Changes in tracking performance were held to reflect attentional shifts. Discrete deviation in visuomotor tracking, typically a pause in tracking, began on average 235 ms after the onset of the balance reaction (TA EMG; average latency 90 ms). Such pauses lasted on average 600 ms, although additional errors in tracking lasted up to 9 s following the perturbation. The findings reveal evidence of dynamic shifts in attention associated with distinct phases of compensatory balance control. The initial phase appears to be triggered automatically, whereas later phases involve varying degrees of attentional resources.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

THE opioid receptor-like (ORL1) receptor regulates a variety of effectors shared by its close relatives, the opioid receptors. Supersensitization of adenylyl cyclase (AC) is a hallmark of cellular tolerance induced by chronic activation of opioid receptors. To examine if chronic activation of the ORL1receptor leads to a similar adaptation, a HEK293 cell line stably expressing the human ORL1receptor (293/ORL1) was established. Chronic treatment of 293/ORL1cells with nociceptin/OFQ resulted in enhanced AC activity in response to forskolin stimulation. The AC supersensitivity was blocked by pertussis toxin, indicating the involvement of Gi/Goproteins. Likewise, chronic activation of endogenous ORL1receptors in the neuroblastoma SKN-SH cells led to Gi/Go-mediated AC supersensitization.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

THE early clinical symptoms of Parkinson's disease (PD) may be difficult to perceive and are frequently overlooked. Thus, interest has focused on the identification of biological or instrumental markers that may contribute to the early diagnosis of PD, with the aim of introducing neuroprotective therapies at the very start of illness. Impairment of nigrostriatal dopamine transmission can be visualizedin vivoby functional imaging techniques, but these are rather complex and expensive examinations, available only in selected institutions. Here we show that dopamine content and tyrosine hydroxylase immunoreactivity are reduced in peripheral blood lymphocytes (PBL) in the early stages of PD. These data suggest that PBL may represent a simple and useful tool with which to identify precociously dopamine impairment in PD.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

WE evaluated the relationship between amyloid-β protein (Aβ) concentration and the metabolic abnormality in an Alzheimer's disease (AD) patient as measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). Across most regions there were significant inverse correlations among FDG-PET intensity values and both insoluble. The temporal lobe samples showed no significant correlation between FDG-PET values and Aβ deposition. Findings support Aβ as contributing to the hypometabolism in regions of the AD brain that are still relatively viable metabolically; those regions with chronic pathologic damage, such as temporal cortex, may have other factors that contribute to metabolic deficits.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

POTENTIAL genomic changes leading to decreased nicotine binding, crucial for cognitive dysfunction in Alzheimer's disease (AD), have not yet been studied. A search for mutations of the genes coding for the most widely distributed nicotinic receptor subtype α4β2 (CHRNA4/CHRNB2) has been performed in AD patients by screening the coding regions of both genes by single strand conformation analysis and heteroduplex analysis of fibroblast-derived genomic DNA. Polymorphisms in CHRNA4, none of which led to amino acid changes in the predicted sequence, were found in three patients. Although the other receptor subunits have yet to be screened, it appears likely that the reduction of nicotine binding sites in AD is not due to genomic changes.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

AGE-ASSOCIATED memory impairment (AAMI) is a clinical entity which was originally described to define memory problems linked to normal aging. Apolipo-protein E and ACE genes have both been associated with cognitive impairment in aging and dementia. The purpose of this study was to investigate memory and executive functions in AAMI according to the genetic background. We found that subjects carrying the Apo E ε4 allele exhibit lower memory performance on tests of both declarative and procedural memory. We did not find differences on frontal lobe tests. These findings give further support to the hypothesis concerning a genetic susceptibility for cognitive impairment in aging.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

OLIGODENDROCYTES are the myelin forming glial cells of the CNS and are known to express receptors linked to ion channels and intracellular second messenger cascades. In this paper, we describe the intracellular calcium responses of cells from the oligodendrocyte lineage to application of lysophosphatidic acid (LPA), a naturally occurring, growth factor-like phospholipid. Oligodendrocyte precursors did not respond to application of LPA (1 μM). In mature oligodendrocytes, however, LPA (1 μM) induced an increase in the intracellular calcium concentration ([Ca2+]i). In the majority of cells this increase was followed by a persistent plateau phase. The LPA-induced [Ca2+]isignal vanished in Ca2+-free medium, implying that it arose due to a Ca2+influx across the plasma membrane. Preincubation of the cells with Pertussis-toxin prevented the generation of LPA-induced [Ca2+]isignals. We conclude that cultured rat oligodendrocytes express functional LPA receptors, which mediate a transmembrane Ca2+influx via a Pertussis-toxin-sensitive G-protein.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID