Lifelong reductions of PKMζ in ventral hippocampus of nonhuman primates exposed to early-life adversity due to unpredictable maternal care

• Published in: Learning & memory (Cold Spring Harbor, N.Y.) Vol. 28; no. 9; pp. 341 - 347
• Main Authors: Fulton, Sasha L., Hsieh, Changchi, Atkin, Tobias, Norris, Ryan, Schoenfeld, Eric, Tsokas, Panayiotis, Fenton, André Antonio, Sacktor, Todd Charlton, Coplan, Jeremy D.
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.09.2021
• Subjects: Animals; Anxiety disorders; Dentate gyrus; Emotions; Hippocampus; Hippocampus - metabolism; Immunohistochemistry; Kinases; Long term memory; Long-Term Potentiation; Macaca radiata; Male; Protein kinase; Protein Kinase C - metabolism; Stress, Psychological; Subiculum
• ISSN: 1549-5485; 1072-0502; 1549-5485
• DOI: 10.1101/lm.053468.121

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.