The uptake of a fluorescently labelled antisense oligonucleotide in vitro and in vivo
| Autor: | David J. Nutt, Alan L. Hudson, Emma S J Robinson, Helen C. Jackson |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cerebral Cortex
Male Adrenergic receptor Oligonucleotide Drug Administration Routes General Neuroscience Receptor expression Biological Transport In Vitro Techniques Biology Molecular biology In vitro Oligodeoxyribonucleotides Antisense Rats Neurotransmitter receptor In vivo Parenchyma Fluorescence microscope Animals Fluorescein Rats Wistar Cells Cultured |
| Zdroj: | Journal of Neuroscience Methods. 147:48-54 |
| ISSN: | 0165-0270 |
| Popis: | Antisense oligonucleotides have been used to target a range of different gene products in the CNS including neurotransmitter receptors. Previous studies using antisense oligonucleotides to target the rat α 2A/D -adrenoceptor revealed changes in receptor expression in specific brain areas following i.c.v. administration but no reduction was observed following antisense treatment in primary cortical neurones. In order to resolve these discrepant results, the uptake and distribution of the antisense sequence has been determined. In vivo, the fluorescent signal was detected close to the site of injection (2–3 mm) and on the same side of the brain as the injection. Although the oligonucleotides (ODN) were distributed throughout the CSF, the ODN was not widely distributed within the mid or hindbrain parenchyma. In vitro uptake studies revealed the antisense was poorly taken up into primary cortical neurones but a higher level of fluorescence was detected in a small sub-population of cells. These studies demonstrate that antisense is rapidly taken up into cells in vivo but poorly taken up into primary cortical neurones in culture. These data provide further evidence for the uptake and distribution of antisense oligonucleotides in neuronal tissue in vivo. |
| Databáze: | OpenAIRE |
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