Pleiotrophin ameliorates age-induced adult hippocampal neurogenesis decline and cognitive dysfunction
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
Affiliations
Haoyang Li
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China
Li Xu
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China
Wei Jiang
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China
Xiusheng Qiu
Vaccine Research Institute, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China
Huiming Xu
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China
Fan Zhu
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China
Yu Hu
Medical Research Center, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China
Shuzhen Liang
Medical Research Center, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China
Chengcheng Cai
Medical Research Center, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China
Wei Qiu
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China; Corresponding author
Zhengqi Lu
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China; Corresponding author
Yaxiong Cui
State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, Beijing Advanced Innovation Center for Structural Biology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; Corresponding author
Changyong Tang
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China; Corresponding author
Summary: 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.
