Mount Sinai Medical Center, New York, New York 10029, USA.
Department of Physiology and Pharmacology.
Learn Mem. 2021 Aug 16;28(9):341-347. doi: 10.1101/lm.053468.121. Print 2021 Sep.
Protein kinase Mζ (PKMζ) maintains long-term potentiation (LTP) and long-term memory through persistent increases in kinase expression. Early-life adversity is a precursor to adult mood and anxiety disorders, in part, through persistent disruption of emotional memory throughout life. Here we subjected 10- to 16-wk-old male bonnet macaques to adversity by a maternal variable-foraging demand paradigm. We then examined PKMζ expression in their ventral hippocampi as 7- to 12-yr-old adults. Quantitative immunohistochemistry reveals decreased PKMζ in dentate gyrus, CA1, and subiculum of subjects who had experienced early-life adversity due to the unpredictability of maternal care. Adult animals with persistent decrements of PKMζ in ventral hippocampus express timid rather than confrontational responses to a human intruder. Persistent down-regulation of PKMζ in the ventral hippocampus might reduce the capacity for emotional memory maintenance and contribute to the long-lasting emotional effects of early-life adversity.
蛋白激酶 Mζ（PKMζ）通过激酶表达的持续增加来维持长时程增强（LTP）和长时程记忆。生命早期逆境是成年情绪和焦虑障碍的前兆，部分原因是通过终生持续破坏情绪记忆。在这里，我们通过母婴可变觅食需求范式使 10 至 16 周龄的雄性冕狐猴经历逆境。然后，我们在 7 至 12 岁的成年时检查了他们的腹侧海马体中的 PKMζ 表达。定量免疫组织化学显示，由于母婴照顾的不可预测性，经历生命早期逆境的个体的齿状回、CA1 和下托中的 PKMζ 减少。腹侧海马体中 PKMζ 持续减少的成年动物对人类入侵者表现出胆怯而不是对抗性的反应。腹侧海马体中 PKMζ 的持续下调可能会降低情绪记忆维持的能力，并导致生命早期逆境的持久情绪影响。
