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Date: January 29, 2026
Time: 11am-12pm EST / 5-6pm CET
Title: Acute CNS Responses to centrally Delivered Oligonucleotides
Description:
Oligonucleotides delivered into cerebrospinal fluid elicit two independent, short-lived CNS phenotypes: an immediate neuronal activation phenotype that appears within minutes and resolves by ~2 hours, and a reversible sedation phenotype that peaks near 3 hours and clears by 24 hours. Across rodents and nonhuman primates, standardized scoring frameworks quantify these behaviors and support cross-species comparison. Activation scales with dose, injected concentration, body weight, and the divalent-ion:oligonucleotide ratio, whereas sedation associates with sequence and phosphorothioate content and with posterior-to-anterior exposure gradients after intrathecal delivery. Together, these observations define distinct kinetics, determinants, and readouts for acute CNS activation and sedation following central oligonucleotide administration.
