Comparing regional brain uptake of incretin receptor agonists after intranasal delivery in CD-1 mice and the APP/PS1 mouse model of Alzheimer’s disease

Table 1 Statistical results (p values) on IRA brain distribution in CD-1 mice

	EXENATIDE			SEMAGLUTIDE			DULAGLUTIDE			DA4-JC			DA5-CH
Region	Time (T)	Sex (S)	T x S	Time (T)	Sex (S)	T x S	Time (T)	Sex (S)	T x S	Time (T)	Sex (S)	T x S	Time (T)	Sex (S)	T x S
WB	0.195	0.202	0.838	0.352	0.599	0.405	0.003*	0.010*	0.083	0.175	0.001*	0.819	0.285	0.905	0.412
Hc	0.613	0.110	0.238	0.727	0.209	0.489	0.625	0.908	0.571	0.114	0.003*	0.161	0.519	0.182	0.703
Neo	0.001*	0.060	0.745	0.15	0.784	0.549	0.002*	0.111	0.228	0.048*	0.002*	0.323	0.188	0.135	0.298
OB	0.064	0.890	0.738	0.281	0.987	0.792	0.259	0.489	0.222	0.291	0.023*	0.613	0.029*	0.823	0.231
FC	< 0.0001*	0.070	0.040*	0.054	0.736	0.517	< 0.0001*	0.551	0.774	0.064	0.010*	0.387	0.070	0.020*	0.270
Str	0.177	0.031*	0.238	0.802	0.231	0.938	0.442	0.339	0.144	0.186	0.170	0.615	0.998	0.010*	0.190
Hy	0.247	0.914	0.34	0.057	0.774	0.846	0.088	0.017*	0.071	0.360	0.399	0.882	0.415	0.170	0.090
Th	0.274	0.659	0.922	0.624	0.483	0.498	0.476	0.495	0.314	0.032*	0.007*	0.722	0.001*	0.122	0.004*
PC	0.393	0.002*	0.849	0.315	0.367	0.345	0.260	0.237	0.614	0.119	0.0001*	0.141	0.072	0.599	0.173
OC	0.283	0.163	0.628	0.378	0.816	0.248	0.001*	0.003*	0.017*	0.113	0.015*	0.736	0.683	0.814	0.232
CB	0.066	0.914	0.554	0.767	0.218	0.299	0.029*	0.056	0.001*	0.241	0.003*	0.204	0.819	0.748	0.153
MBr	0.874	0.702	0.705	0.243	0.517	0.29	0.013*	0.018*	0.005*	0.006*	0.034*	0.248	0.158	0.452	0.100
Po	0.718	0.080	0.625	0.567	0.363	0.345	0.060	0.873	0.133	0.048*	0.009*	0.753	0.087	0.979	0.467
Ser	0.028*	0.012*	0.868	< 0.0001*	0.219	0.075	0.0002*	0.441	0.863	0.230	0.007*	0.435	0.0006*	0.678	0.828

Mean %Inj/g or %Inj/ml (Ser) levels ± SEM were compared within each IRA and within each brain region with respect to time after IN delivery (5, 15, 30, or 60 min) or sex (male or female) or the interaction between time and sex (T x S). Overall ANOVA results are presented with statistical significance (*) defined as p < 0.05. Total “n” for each IRA: exenatide n = 4–5/sex/timepoint, semaglutide n = 3–5/sex/timepoint, dulaglutide n = 4–5/sex/timepoint, DA4-JC n = 4/sex/timepoint, DA5-CH n = 4–5/sex/timepoint. Post-hoc analyses are reported in Supplemental Table 1. WB = whole brain, Hc = hippocampus, Neo = neocortex (frontal + parietal + occipital), OB = olfactory bulb, FC = frontal cortex, Str = striatum, Hy = hypothalamus, Th = thalamus, PC = parietal cortex, OC = occipital cortex, CB = cerebellum, MBr = midbrain, Po = pons/medulla, Ser = serum

ISSN: 1758-9193