2. Academic Validation
  3. Pleiotrophin ameliorates age-induced adult hippocampal neurogenesis decline and cognitive dysfunction

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

  • Cell Rep. 2023 Aug 22;42(9):113022. doi: 10.1016/j.celrep.2023.113022.
Haoyang Li 1,  Li Xu 1,  Wei Jiang 1,  Xiusheng Qiu 2,  Huiming Xu 1,  Fan Zhu 1,  Yu Hu 3,  Shuzhen Liang 3,  Chengcheng Cai 3,  Wei Qiu 4,  Zhengqi Lu 5,  Yaxiong Cui 6,  Changyong Tang 7
Affiliations

Affiliations

  • 1 Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China.
  • 2 Vaccine Research Institute, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China.
  • 3 Medical Research Center, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China.
  • 4 Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. Electronic address: qiuwei120@vip.163.com.
  • 5 Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. Electronic address: luzhq@mail.sysu.edu.cn.
  • 6 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. Electronic address: cuimarcus@mail.tsinghua.edu.cn.
  • 7 Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. Electronic address: tangchy23@mail.sysu.edu.cn.
PMID: 37610873 DOI: 10.1016/j.celrep.2023.113022
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.

Keywords

CP: Neuroscience.

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