摘要:

GLOBOID cell leukodystrophy (GCL or Krabbe disease) is a recessive disease caused by mutations of the lysosomal enzyme galactocerebrosidase (GALC) and twitcher is the murine model of GCL. We have prepared retroviral packaging cell lines to transduce the GALC gene. Retroviral transduction restored GALC activity in GCL fibroblasts and increased such activity to very high levels in immortalized neural progenitor cells (ST14A cells). GALC activity was also normalized in twitcher fibroblasts co-cultured with ST14A cells over-expressing GALC, demonstrating that this enzyme is secreted and can be imported efficiently by GALC-deficient cells. These results give the necessary background to evaluate the therapeutic effect in twitcher of brain grafting of neural progenitor cells engineered to release high levels of GALC.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

To gain insight into the role of striatal dopamine in basal ganglia functioning, dopaminergic drugs alone and in combination with the glutamate receptor agonist kainic acid were infused in the lateral striatum via a microdialysis probe, while single-unit recordings of substantia nigra reticulata neurons were made in chloral hydrate-anaesthetized rats. Striatal infusion of dopaminergic drugs did not significantly affect the firing rate of substantia nigra reticulata neurons, which was related to the low activity of striatal cells under basal conditions, illustrated by the lack of effect of striatal infusion of TTX on substantia nigra reticulata activity. Under glutamate-stimulated conditions, striatal infusion ofd-amphetamine potentiated the inhibition of substantia nigra reticulata neurons induced by striatal kainic acid. Thus, under stimulated but not basal conditions, the modulatory role of dopamine in the striatum could be demonstrated. Dopamine potentiated the inhibitory effect of striatal kainic acid on the firing rate of the basal ganglia output neurons.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

THE aim of this study was to compare the capacity of extracellular matrix (ECM) components to support the growth and differentiation of olfactory tissuein vitro. Reconstituted basement membrane matrix (RBM) supported profuse neurite outgrowth from explants of olfactory bulb (OB), with no non-neuronal cell migration. In contrast, nasal tissue (NT) explants cultured on RBM produced profuse fibroblastic outgrowth, but no neurite outgrowth from olfactory sensory neurones (OSN). Three-dimensional collagen gels, on the other hand, supported extensive outgrowth of both nonneuronal and neurite outgrowth from OB and NT explants, mature OSNs in the latter being identified using antibodies against olfactory marker protein (OMP). These culture systems represent useful tools for investigating potential tropic influences of target tissue.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

STATIC vestibulo-ocular brain stem syndromes characterized by skew deviation, a vertical disconjugacy of the eyes, and ocular torsion are the result of a vestibular tone imbalance in the frontal (roll) plane. Similar physiological changes in static eye position, ocular counter-roll and conjugated deviations of vertical eye position, are caused by the influence of gravity mediated by the utricles. These observations prompted our approach with the model described here: based on the known deviations of static eye position, we devised a three-dimensional mathematical model of otolith–ocular function including detailed brain stem anatomy. This model is able to explain and predict the differential effects of unilateral and bilateral peripheral or central vestibular lesions on static eye position in roll, pitch, and yaw planes.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

CALRETININ and calbindin D28K were localized in the superficial layers of rabbit superior colliculus (SC). Calretinin and calbindin D28K-immunoreactive (-IR) neurons were concentrated in the upper superficial gray layer. Calretinin-IR fibers were found in the optic layer. The majority of calretinin-IR cells were small-to medium-sized vertical fusiform neurons and neurons with round or stellate-shaped somas with small varicose dendrites. The morphology of calbindin D28 K-IR neurons was different from that of calretinin neurons. Anti-calbindin D28K-IR neurons usually had fusiform cell bodies and a thick primary dendrite with small branches forming a dendritic bouquet. Two-color immunofluorescence revealed that no cells expressed both proteins. Following unilateral enucleation a marked reduction of calretinin-IR fibers in the contralateral side to the enucleation was found. Enucleation appeared to have no effect on the cell bodies labeled with either protein. The results suggest the anti-calretinin immuno-reactivity in the superficial layer of rabbit SC contrasts starkly with that of other animals.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

THE cortical areas subserving music literacy were investigated using high-field (3 Tesla) functional magnetic resonance imaging (fMRI). The activation pattern associated specifically with music score reading was compared with that associated with reading text in a subject's primary and secondary language. While the areas of activation were predominantly identical for all three reading modalities, there were areas within the occipital cortex activated exclusively by music score reading. Grand analysis of the activation patterns of eight pianists unequivocally identified that the principal cortical area needed for music literacy is the cortex flanking the right transverse occipital sulcus (musical brain).

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ALZHEIMER'S disease (AD), a progressive neurodegenerative disorder, is diagnosed definitively by increased numbers of β-amyloid plaques and neurofibrillary tangles in brain biopsy or autopsy specimens. There are no simple straightforward laboratory tests currently available for clinical diagnosis. We have found consistent reduction in mitotic index levels in skin fibroblast cultures from AD individuals compared with age-and sex-matched controls. These differences were enhanced by overnight exposure to colcemid (p= 0.04). Results suggest that mitotic index in skin fibroblasts cultures should be further investigated as a potential diagnostic indicator for AD.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

USING a dialysis electrode, we recently developed an oxygen-independent system for real-time measurement of the glutamate concentration in the extracellular space ([Glu]e) during ischemia. This system allows separate evaluation of intra-ischemic biphase [Glu]e elevation, i. e. release from synaptic vesicles (1st phase), reversed uptake of glutamate from metabolic pools in neuronal cells (2nd phase), and post-ischemic glutamate re-uptake in ischemia—reperfusion models. Using the system, we attempted to clarify the relationship between biphase glutamate release and brain temperature in a model of acute global ischemia produced by transecting both carotid arteries. Our results showed that, in contrast to mild hyperthermia, hypothermia did not inhibit the 1st phase of [Glu]e release, and changes in intra-ischemic brain temperature had a minimal effect on the 2nd phase of [Glu]e elevation during severe acute ischemia. These findings, together with our previous data, indicate that brain temperature change in the intra-ischemic period plays an important role in disturbance of the glutamate re-uptake system during ischemia.NeuroReport9: 3863–3868 © 1998 Lippincott Williams & Wilkins.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

CYCLOOXYGENASE (COX)-2 is constitutively expressed in the superficial dorsal horn of the spinal cord, but its role in the spinal cord is still unclear. We examined the effect of intrathecally administered NS398, a selective COX-2 inhibitor and indomethacin, an non-selective COX-1 and COX-2 inhibitor, on the development of thermal hyperalgesia induced by the activation of NMDA or AMPA receptors. Intrathecal injection of either NS398 or indomethacin equally blocked the development of thermal hyperalgesia induced by intrathecal injection of either NMDA or AMPA in a dose-dependent manner. These data suggest that COX-2 plays an important role in spinal thermal nociceptive transmission when neurons in the spinal cord are facilitated by NMDA or AMPA.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

NUMEROUS lines of evidence suggest that some of the neurotoxicity associated with Alzheimer's disease (AD) is due to proteolytic fragments of the amyloid precursor protein (APP). Most research has focused on the amyloid β peptide (A β). However, the possible role of other cleaved products of APP is less clear. In this study, the effects of a recombinant carboxy terminal 105 amino acid (CT105) fragment of APP on the calcium uptake by endoplasmic reticulum Mg2+-Ca2+ATPase, the major mechanism for sequestering calcium in this orgenelle, were investigated. We found that CT 105 is a potent inhibitor of Mg2+-Ca2+ATPase of endoplasmic reticulum, whereasAβ shows no effect. These results demonstrate that CT 105 inhibits the ability of brain microsomes to sequester calcium and suggest that this inhibitory effect of CT 105 may contribute to disruption of intracellular calcium concentration, possibly being involved in inducing the neural toxicity characteristic of AD.NeuroRepor t9: 3875–3879 © 1998 Lippincott Williams & Wilkins.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID