Mancini Camilla, Babicola Lucy, Chila Gilda, Di Segni Matteo, Municchi Diana, D'Addario Sebastian Luca, Spoleti Elena, Passeri Alice, Cifani Carlo, Andolina Diego, Cabib Simona, Ferlazzo Fabio, Iosa Marco, Rossi Rodolfo, Di Lorenzo Giorgio, Renzi Massimiliano, Ventura Rossella
University of Camerino, School of Pharmacy, Pharmacology Unit, Camerino, Italy.
IRCCS Santa Lucia Foundation, Rome, Italy.
iScience. 2024 Nov 21;27(12):111328. doi: 10.1016/j.isci.2024.111328. eCollection 2024 Dec 20.
Although clinically relevant, evidence for a protective effect of early secure attachment against the development of depressive symptoms in adulthood is still inconsistent. This study used a translational approach to overcome this limitation. The analysis of a non-clinical adult population revealed a moderating effect of secure attachment on depressive symptoms in women only. Thus, we tested the causal link between early attachment with caregiver and adult depressive-like phenotypes in a mouse model of early adversities that is especially effective in females. Repeated cross fostering (RCF) in the first postnatal days prevented the development of pups' secure attachment with the caregiver as tested in a rodent version of the "strange situation"-the standard human test-induced depressive-like behaviors and altered activity of the ventral tegmental area dopamine neurons in adulthood. Finally, a stable alternative caregiver during the RCF experience prevented all these effects, modeling human "earned attachment."
尽管具有临床相关性,但早期安全型依恋对成年期抑郁症状发展具有保护作用的证据仍然不一致。本研究采用转化方法来克服这一局限性。对非临床成年人群的分析显示,安全型依恋仅对女性的抑郁症状有调节作用。因此,我们在早期逆境的小鼠模型中测试了早期与照顾者的依恋关系与成年期抑郁样表型之间的因果联系,该模型对雌性小鼠特别有效。出生后早期的反复交叉寄养(RCF)阻碍了幼崽与照顾者形成安全型依恋,这在啮齿动物版的“陌生情境”测试中得到了验证——这是一种标准的人类测试,会诱发成年期的抑郁样行为,并改变腹侧被盖区多巴胺神经元的活动。最后,在RCF期间有一个稳定的替代照顾者可以防止所有这些影响,模拟了人类的“获得性依恋”。