摘要:

INTRACEREBRAL or intraspinal grafting of genetically modified primary fibroblasts has been shown to enhance functional recovery in several models of CNS disease, including spinal cord injury. Most of these studies utilized retrovirus vectors. In this report, we describein vitroconditions for genetically modifying primary fibroblasts with recombinant adenovirus vectors carrying the lacZ or green fluorescent protein (GFP) genes. As intraspinal allografts in animals immunosuppressed by cyclosporin A, the genetically modified cells survived and expressed the transgenes for at least 2 months. We conclude that recombinant adenovirus vectors are efficient and convenient tools forex vivogene therapy in the CNS.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Nociceptin (orphanin FQ), the newly discovered endogenous ligand for the opioid receptor like-1 receptor, profoundly inhibited spontaneous discharges of neurons in the rostral ventrolateral medulla (RVLM) in rat brain slices. This inhibition was concentration-dependent (0.3, 1, 3 and 10 nM) and insensitive to pharmacological blockade of traditional opioid receptors by naloxone. Moreover, nociceptin injected into the RVLM (10 nM, 0.1 μl) in anesthetized rats decreased arterial blood pressure and heart rate by 31% and 15%, respectively. The data obtainedin vitroandin vivosuggest that nociceptin has powerful effects on the RVLM neurons involving central control of cardiovascular activity. The negative regulation of cardiovascular activity by nociceptin is not mediated through typical naloxone-sensitive opioid receptors.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The motoneurones with axons in the common peroneal nerve (CPN) of the rat and monkey were examined using retrograde labelling with horseradish peroxidase (HRP). In both species, the CPN motoneurone pool was localized in the dorsolateral part of the ventral horn of the spinal cord. In the rat, the labelled motoneurones were located between the L3 and L6 spinal segments whereas in the monkey, they extended from the caudal end of L4 to the L6 spinal segments. In both species the majority of the labelled neurones were located within the L5 segment. The mean number of the CPN motoneurones in the rat and monkey was 458 and 1148, respectively. A bimodal size distribution of motoneurones was found in both species.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The effect of nitric oxide (NO) on GABA induced Cl−current of recombinant GABAAreceptors was studied. Either α1β2γ2sor α1β2subunit mRNAs synthesized from cDNA of mouse brain were injected intoXenopusoocytes and functional GABAAreceptors were expressed. GABA-induced Cl−current was measured with the two electrode voltage clamp technique. The NO donor NOC-18 reduced the GABA-induced Cl−current in the α1β2γ2ssubunit receptor in a dose-dependent manner. In α1,β2subunit receptor, NOC-18 had no effects on GABA-induced currents at low concentrations but showed potentiation at high concentration. These effects were antagonized by the NO extinguisher, carboxy-PTIO. The cGMP analogue 8-Br-cGMP failed to induce NO-like effects. NO directly acts at the GABAAreceptor and the γ2ssubunit is involved in its action.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Neural transplantation is an experimental therapy for Parkinson's disease. Pretreatment of fetal donor tissue with neurotrophic factors may improve survival of grafted dopaminergic neurons. Free-floating roller tube cultures of fetal rat ventral mesencephalon were treated with brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), or a combination of both. Dopamine content of the culture medium, the number of tyrosine hydroxylase-immunoreactive neurons, and culture volumes were moderately increased in the BDNF- and GDNF-treated cultures but significantly increased by 6.8-, 3.2- and 2.4- fold, respectively after treatment with the combination of both factors. We conclude that pretreatment of dopaminergic tissue in culture with a combination of BDNF and GDNF may be an effective means to improve the quality of tissue prior to grafting.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Low-Stringency PCR was used to isolate the chicken homologue of the human bone morphogenetic protein receptor type II (BMPR-II).In situhybridization localized mRNA expression for this serine/threonine kinase receptor. It was weakly expressed in the vitreal side of the neural retina at E6. In the E7 chicken, fairly strong labelling was found in cells of the internal part of the neural retina. At E9, strong labelling was found in the region of the retinal ganglion cells. Explants of E6 retina exposed to osteogenic protein-1 (OP-1/BMP-7), exhibited dense retinal fibre outgrowth. This suggests that BMPR-II may form a signalling receptor complex important for retinal development. OP-1 and related ligands may serve functions supplementary to those of neurotrophins.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PREVIOUS studies have shown that transgenic mice over-expressing NGF in the skin have novel sympathetic ‘basket-like’ projections to sensory neurons similar to that seen in models of chronic pain. Since only a subset of sensory neurons in the NGF-transgenic mice received the sympathetic projections, we hypothesized that sympathetic sprouting was targeted to those neurons affected by increased levels of NGF. To test this, doublelabel immunohistochemistry for the NGF receptor (trkA) and sympathetic baskets was performed. Thirty-nine percent of all neurons in transgenic trigeminal ganglia were trkA-positive. Moreover, of the population of sensory neurons that received sympathetic input, 84% were trkA-positive. These results indicate that retrogradely transported NGF can induce and direct growth of sympathetic axonsin vivo.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

THE acid sensing ion channel (ASIC) identified in rat brain and spinal cord is potentially involved in the transmission of acid-induced nociception. We have developed polyclonal antisera against ASIC, and used them to screen rat brain and spinal cord using immunocyto-chemistry. ASIC-immunoreactivity (-ir) is present in but not limited to the superficial dorsal horn, the dorsal root ganglia (DRG) and the spinal trigeminal nucleus, as well as peripheral nerve fibers. These observations, combined with the disappearance of ASIC-ir following dorsal rhizotomy, suggest localization of ASIC to primary afferents. DRG ASIC-ir co-localizes with substance P (SP) and calcitonin gene-related peptide (CGRP)-ir in small capsaicin-sensitive cell bodies, suggesting that ASIC is poised to play a role in the transduction of noxious stimuli.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Behavioral and patient studies have suggested that during dichotic listening the ipsilateral auditory pathways are strongly inhibited, so that each hemisphere is treats the sound coming to the contralateral ear. We analysed the auditory N100m neuromagnetic evoked response following passive listening of dichotic tones of different frequencies. We found that the N100m in each hemisphere depended on both ipsilateral and contralateral stimuli, revealing no strong inhibition of ipsilateral pathways. The N100m increased with the interaural frequency disparity and was reduced as both ears received identical stimuli. The results can be explained by the existence of a frequency-dependent excitatory/inhibitory organization of the auditory cortex, as has been described in the cat. We suggest that the N100m might also reflect automatic processes involved in multiple-stream perception.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

CHANGES in neuronal Ca2+homeostasis were studied on freshly isolated dorsal root ganglion neurons of adult control mice and mice with streptozotocin (STZ)-induced diabetes. The cytoplasmic free Ca2+concentration ([Ca2+]in) was measured using indo-1 based microfluorimetry. The participation of mitochondria in [Ca2+]inhomeostasis was determined by investigation of changes which occurred after addition of mitochondrial protonophore (CCCP) to the extracellular solution. In control cells 10 μM CCCP applied before membrane depolarization induced an increase of the amplitude of depolarization-induced [Ca2+]intransients and disappearance of their delayed recovery, indicating the participation of mitochondria in fast uptake of Ca2+ions from the cytosol during the peak of the transient and subsequent slow release them back during its decay. In diabetic animals the increase of the peak transient amplitude under the action of CCCP became diminished in small (nociceptive) neurons and the delayed elevation of [Ca2+]indisappeared in both large and small neurons. It is concluded that in diabetic conditions substantial changes occur in the Ca2+homeostatic functions of mitochondria, manifested by decreased Ca2+uptake in small neurons and depressed Ca2+release into the cytosol in all types of neurons.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID