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Bart Nuttin

Publications and source records attributed to Bart Nuttin.

6 recordsLinked to original sources
PubMed2003

Lentiviral vector-mediated delivery of short hairpin RNA results in persistent knockdown of gene expression in mouse brain.

RNA interference (RNAi) is an evolutionarily conserved mechanism of posttranscriptional gene-specific silencing. For in vivo applications, RNAi has been hampered until recently by inefficient delivery methods and by the transient nature of the gene suppression. Lentiviral vectors (LVs) hold great promise for gene therapeutic applications, pharmaceutical target validation, and functional genomics because stable gene transfer is mediated both in dividing and nondividing cells. We have used a lentiviral vector-based system for RNAi. We produced human immunodeficiency virus type 1-derived LVs encoding a short hairpin RNA specific for enhanced green fluorescent protein (EGFP) mRNA that were capable of inhibiting EGFP expression in mammalian cells. EGFP knockdown persisted after multiple passages of the cells. Of particular interest, our RNAi LVs were equally effective in suppression and prevention of EGFP expression after stereotactic injection in adult mouse brain. Therefore, we believe that the use of LVs for stable RNAi in brain will become a powerful aid to probe gene function in vivo and for gene therapy of diseases of the central nervous system.

Animals↗
PubMed2003

Effects of electrical stimulation or lesion in nucleus accumbens on the behaviour of rats in a T-maze after administration of 8-OH-DPAT or vehicle.

Electrical brain stimulation may be a therapeutic alternative for irreversible lesions in treatment-resistant patients with obsessive-compulsive disorder (OCD). We compared the effects of electrical stimulation and lesion in the nucleus accumbens (n acc) on the behaviour of rats in a model for OCD. Rats were tested for spontaneous alternation behaviour (AB) in a T-maze and assigned to four groups: an electrode implant group with stimulation 'ON' (stimON) or 'OFF' (stimOFF), a lesion or a sham group. Postoperatively, the number of arm visits and AB were tested after 8-hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT; 2 mg/kg) or saline administration. After 8-OH-DPAT administration, more arm visits were counted in the stimON (92.2%) and lesion groups (79.3%) than in both control groups (stimOFF 54.2; sham 61.2%). AB was significantly decreased in the stimON (10.5%) and lesion groups (10.2%) relative to the sham (22.0%) but not to the stimOFF group (14.7%). After saline administration, rats performed more arm visits in the stimON (81.5% non-significant) and lesion groups (93.6% significant) relative to the stimOFF (70.8%) and the sham groups (74.5%). No significant differences, however, were observed for AB. In conclusion, both treatments resulted in a decreased AB after 8-OH-DPAT administration (modelling an increase in compulsions) and more arm visits.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2003

Neuropathology and neurodegeneration in rodent brain induced by lentiviral vector-mediated overexpression of alpha-synuclein.

Two mutations in alpha-synuclein, the main constituent of Lewy bodies, have been identified in familial Parkinson's disease. We have stereotactically injected lentiviral vectors encoding wild-type and A30P mutant human alpha-synuclein in different brain regions (striatum, substantia nigra, amygdala) of mice. Overexpression of alpha-synuclein induced time-dependent neuropathological changes reminiscent of Lewy pathology: abnormal accumulation of alpha-synuclein in cell bodies and neurites, alpha-synuclein-positive neuritic varicosities and cytoplasmic inclusions that stained with ubiquitin antibodies and became larger and more frequent with time. After one year, alpha-synuclein- and ubiquitin-positive neurons displayed a degenerative morphology and a significant loss of alpha-synuclein-positive cells was observed. Similar findings were observed with both the wild-type and the A30P mutant form of alpha-synuclein and this in different brain regions. This indicates that overexpression of alpha-synuclein is sufficient to induce Lewy-like pathology and neurodegeneration and that this effect is not restricted to dopaminergic cells. Our data also demonstrate the use of lentiviral vectors to create animal models for neurodegenerative diseases.

Amygdala↗
PubMed2002

Characterization of lentiviral vector-mediated gene transfer in adult mouse brain.

Lentiviral vectors are promising tools for gene transfer into the central nervous system. We have characterized in detail transduction with human immunodeficiency virus type 1 (HIV-1)-derived vectors encoding enhanced green fluorescent protein (eGFP) in the adult mouse brain. Different brain regions such as the striatum, hippocampus, and the lateral ventricle were targeted. The eGFP protein was transported anterogradely in the nigrostriatal pathway, but we have found no evidence of transport of the lentiviral vector particle. The performance levels of the different generations of packaging and transfer plasmid were compared. Omission of the accessory genes from the packaging plasmid resulted in a modest decrease in transgene expression. Inclusion of the woodchuck hepatitis posttranscriptional regulatory element, on the one hand, and the central polypurine tract and termination sequences, on the other hand, in the transfer vector each resulted in a 4- to 5-fold increase in transgene expression levels. Combination of both elements enhanced expression levels more than the sum of the individual components, suggesting a synergistic effect. In the serum of mice injected with lentiviral vectors a humoral response to vector proteins was detected, but this did not compromise transgene expression. Immune response to the transgene was found only in a minority of the animals.

Animals↗
PubMed1994

Spinal cord stimulation in Belgium: a nation-wide survey on the incidence, indications and therapeutic efficacy by the health insurer.

The present report describes a nation-wide survey on the incidence, the indications and the efficacy of spinal cord stimulation (SCS), as assessed by the Belgian health authorities. The direct motive for this survey was the rapidly growing expenditures resulting from the increasing use of SCS. Between 1983 and 1992, nearly 700 SCS devices were implanted for a population of less than 10 million inhabitants. The most common indication for SCS was failed back survey (61.4%). Whereas SCS was initially only performed in university teaching hospitals, it is now also widely practised in general hospitals. In 3 studies, the efficacy of SCS was assessed. In a first study, success was defined in terms of resumption of professional activities. After a mean follow-up of more than 1 year, less than 5% of the 147 patients treated with SCS had returned to work. A second study investigated the subjective evaluation of the therapy by the patient. Seventy patients with a mean follow-up of 3.5 years were studied. In 52% of the patients, the effect of SCS was judged as good to very good. Men scored better than women. In addition, the results obtained in the teaching hospitals were significantly better than those obtained in general hospitals. In a third study, the impact of psychiatric screening on patient selection was evaluated. Of the 100 candidates, 36 were withheld from implantation with a SCS device because of psychiatric contra-indications. Patients who had received a positive psychiatric advice showed a significantly better therapeutic outcome than patients for whom the psychiatrist had made reservations.

Adolescent↗