Pleiotrophin ameliorates age-induced adult hippocampal neurogenesis decline and cognitive dysfunction.

Abstract

Cognitive impairment has been associated with an age-related decline in adult hippocampal neurogenesis (AHN). The molecular basis of declining neurogenesis in the aging hippocampus remains to be elucidated. Here, we show that pleiotrophin (PTN) expression is decreased with aging in neural stem and progenitor cells (NSPCs). Mice lacking PTN exhibit impaired AHN accompanied by poor learning and memory. Mechanistically, we find that PTN engages with protein tyrosine phosphatase receptor type Z1 (PTPRZ1) to promote NSPC proliferation and differentiation by activating AKT signaling. PTN overexpression or pharmacological activation of AKT signaling in aging mice restores AHN and alleviates relevant memory deficits. Importantly, we also find that PTN overexpression improves impaired neurogenesis in senescence-accelerated mouse prone 8 (SAMP8) mice. We further confirm that PTN is required for enriched environment-induced increases in AHN. These results corroborate the significance of AHN in aging and reveal a possible therapeutic intervention by targeting PTN.

• Authors: Haoyang Li, Li Xu, Wei Jiang, Xiusheng Qiu, Huiming Xu, Fan Zhu, Yu Hu, Shuzhen Liang, Chengcheng Cai, Wei Qiu, Zhengqi Lu, Yaxiong Cui, Changyong Tang
• Journal: Cell reports (Cell Rep) Vol. 42 Issue 9 Pg. 113022 (09 26 2023) ISSN: 2211-1247 [Electronic] United States
• PMID: 37610873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• pleiotrophin
• Proto-Oncogene Proteins c-akt

Topics

• Mice
• Animals
• Proto-Oncogene Proteins c-akt (metabolism)
• Hippocampus (metabolism)
• Neurogenesis (physiology)
• Cognitive Dysfunction