Figure 4.

Ammonia Metabolism after Exogenous Ammonia Loading

(A) After a marked increase with exogenous administration of ¹⁵NH₄Cl, plasma ammonia levels decrease toward baseline over 90 min in female sAAV-treated mice (red line), albeit less rapidly than in wild-type mice (blue line). In male sAAV-treated mice plasma ammonia levels do not decline (orange line). Asterisks denote significant deviation from baseline values within a gender. (Treated male mice data at 60 and 90 min was n = 2 per time point due to animal deaths, along with large value variation accounts for statistical non-significance.) (B) ¹⁵N-labeled urea is produced in mice treated with ¹⁵NH₄Cl, with enrichment peaking faster in wild-type mice (blue, black) than in sAAV-treated mice (red, orange) of both genders. Legend is also shared with (A). (A and B: for females at all time points and experimental groups: n = 5 per group. For males: n = 5 at time 0, n = 4 at time 20, and n = 2 at times 60 and 90 in the treated group due to animal deaths from seizure activity; n = 5 at all times for the wild-type males.) (C) Instantaneous rate of ureagenesis in female (n = 5, both groups) and male mice (n = 4 sAAV-treated and n = 5 wild-type), based on best-fit curves from (B). Data represent mean values ± SEM. Asterisks denote significant deviation from baseline values in the ammonia curves and wild-type values in the urea curves; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.