IGF‐I modulation of emotion and social interaction through Locus Coeruleus in aging and AD mice

Abstract Background Insulin‐like Growth Factor I (IGF‐I) is a peptide involved in many processes in the brain. Recently, we described how IGF‐I modulates sleep behavior, response to stress, and its role in cognition through cholinergic, orexinergic, and locus coeruleus nuclei. Nonetheless, IGF‐I modulation of social behavior remains explored, especially during aging and Alzheimer’s disease pathology. This study aims to determine how IGF‐I modulates emotion and social behavior through Locus Coeruleus activity in young (<6m), middle‐aged (<12m, and old control (>18m), transgenic APP/PS1 and DPS‐4 mice, from the same ages. Method We use extensive behavioral testing of cognition (Y Maze spontaneous activity) and emotion (Forced Swim Test, Elevated Plus Maze), social interaction (Social affiliation and social novelty/Preference), and another test. We also use electrophysiology to determine LC responses to IGF‐I as DPS‐4 neurotoxin to evaluate the role of LC in emotion and social interaction. Results We now report that social behavior is reduced through aging in control mice, even after the cognitive decline. Moreover, APP/PS1 present similar social interaction alterations to old C57 mice (>18m). Further, the activation of electrically stimulated LH neurons by local IGF‐I in young mice was reduced in middle‐aged and aged mice. Middle‐age C57 mice injected with DSP‐4 mice and APP/PS1 present disrupted social behavior and LC activity. Conclusion Consequently, IGF‐I can activate and modulate LC responses with our results. Social and emotional disturbances may be related to IGF‐I resistance in LC, reflecting a broader loss of IGF‐I activity in the aged mouse brain.