The study shows that some modified versions of the sleep‑inducing peptide DSIP get into the rat brain better than others when injected into the bloodstream. In particular, versions with a D‑alanine at position 4 (and a version missing the first tryptophan) cross the blood‑brain barrier more efficiently, and this effect is stronger in larger/older rats. The findings suggest that the brain entry of DSIP isn’t just random leakage but may be selective.

Delta sleep-inducing peptide (DSIP) or five closely related peptides were injected peripherally and the levels of DSIP-like immunoreactivity measured in the brains of 100 g and 500 g rats decapitated a minute later after washout with 0.9% NaCl. Higher concentrations of immunoreactive material were found in brain tissue with injection of des Trp1-DSIP, D-Ala4-DSIP, and, after correction for cross-reactivity, with D-Ala4-DSIP-NH2 than with the other peptides. Both peptides substituted in the fourth position with D-alanine resulted in higher concentrations in 500 g rats than in 100 g rats, indicating a possible effect of age. The 5-10 fold greater brain to blood ratios of radioactivity after 125I-N-Tyr-DSIP than after 125-I radioiodinated serum albumin (RISA) provided additional evidence against non-specific leakage or contamination of the brains with substantial amounts of residual blood. The results suggest that penetration of the blood-brain barrier (BBB) by small amounts of peptides, at least DSIP peptides, may be somewhat selective.