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Distribution of phosphodiester and phosphorothioate oligonucleotides in rat brain after intraventricular and intrahippocampal administration determined by in situ hybridization

Yaida, Yutaka, Nowak, Thaddeus S.·1995·Regulatory Peptides
DOI 10.1016/0167-0115(95)00100-p
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Abstract

The distribution and stability of exogenously administered oligonucleotides (oligos) are important variables determining the potential utility of antisense oligos as agents for modifying gene expression within a given brain region in vivo. In the present study, phosphodiester (PO) and phosphorothioate (PS) oligos antisense with respect to a recently cloned rat hsp70 sequence were localized in rat brain following intraventricular and intrahippocampal administration using an in situ hybridization detection method. Unlabeled PO and PS oligos were dissolved in artificial cerebrospinal fluid and infused under stereotaxic control using a syringe pump. At various intervals after administration frozen brain sections were collected on gelatin-coated slides and hybridized with 35S-labeled probe consisting of the corresponding phosphodiester sense sequence. After intraventricular administration the unmodified PO oligo exhibited a limited and strictly periventricular distribution. In contrast the PS oligo showed significant penetration into and accumulation within brain, with extensive uptake in ipsilateral striatum and dorsal hippocampus, as well as in midline periventricular structures. Both oligos remained detectable for at least two days after administration. Following intrahippocampal injection the PO oligo was rapidly lost from the injection site, with detectable signal persisting only along the hippocampal fissure at 24 h. The PS oligo exhibited a more diffuse initial distribution…

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Research works printed but not linked: 22

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Metadata

Authors
Yaida, Y., & Nowak, T. S.
Venue
Regulatory Peptides
Publisher
Elsevier BV
Published
1995-10
Volume
59
Issue
2
Pages
193-199
ISSN
0167-0115
DOI
10.1016/0167-0115(95)00100-p
Cited by
38
References
0
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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