CELLULAR UPTAKE OF INTRACEREBRALLY ADMINISTERED OLIGODEOXYNUCLEOTIDESIN MOUSE-BRAIN

Intracerebral diffusion, cellular uptake and intracellular localizatio n of oligodeoxynucleotides (ODN) after their microinjection in mouse b rains were examined. Using either tetramethylrhodamine-5-(and -6)-isot hiocyanate (TRITC)- or gamma-P-33 ATP-labeled ODNs, it was found that both phosphodiester ODNs (D-ODN) and phosphorothioate ODNs (S-ODN) qui ckly diffused (up to about 500 mu m) and were taken up by many cells a round the injection site as early as 15 min after administration. Fluo rescence labeling intensity and silver grain accumulation of D-ODNs we re greatly reduced by 4 h after injection, whereas those of S-ODNs wer e stable beyond at least 8 h after injection. Most of labeled ODNs wer e found in neuronal cells as identified by immunocytochemistry for neu rofilament, NF 200, and to a much lesser extent in astrocytic cells as identified by immunocytochemistry for glial fibrillary acidic protein .