Adiporon treatment induces a dose‐dependent response in adult hippocampal neurogenesis

Thomas H. Lee, Brian R. Christie, Henriette van Praag, Kangguang Lin, Parco Ming Fai Siu, Aimin Xu, Kwok Fai So, Suk Yu Yau (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

1 Citation (Scopus)

Abstract

AdipoRon, an adiponectin receptor agonist, elicits similar antidiabetic, anti–atherogenic, and anti–inflammatory effects on mouse models as adiponectin does. Since AdipoRon can cross the blood–brain barrier, its chronic effects on regulating hippocampal function are yet to be examined. This study investigated whether AdipoRon treatment promotes hippocampal neurogenesis and spatial recognition memory in a dose–dependent manner. Adolescent male C57BL/6J mice received continuous treatment of either 20 mg/kg (low dose) or 50 mg/kg (high dose) AdipoRon or vehicle intraperitoneally for 14 days, followed by the open field test to examine anxiety and locomotor ac-tivity, and the Y maze test to examine hippocampal–dependent spatial recognition memory. Im-munopositive cell markers of neural progenitor cells, immature neurons, and newborn cells in the hippocampal dentate gyrus were quantified. Immunosorbent assays were used to measure the serum levels of factors that can regulate hippocampal neurogenesis, including adiponectin, brain– derived neurotrophic factor (BDNF), and corticosterone. Our results showed that 20 mg/kg Adipo‐ Ron treatment significantly promoted hippocampal cell proliferation and increased serum levels of adiponectin and BDNF, though there were no effects on spatial recognition memory and locomotor activity. On the contrary, 50 mg/kg AdipoRon treatment impaired spatial recognition memory, sup-pressed cell proliferation, neuronal differentiation, and cell survival associated with reduced serum levels of BDNF and adiponectin. The results suggest that a low‐dose AdipoRon treatment promotes hippocampal cell proliferation, while a high–dose AdipoRon treatment is detrimental to the hippo-campus function.

Original languageEnglish
Article number2068
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume22
Issue number4
DOIs
Publication statusPublished - 19 Feb 2021

Keywords

  • Adiponectin
  • AdipoRon
  • Brain–de-rived neurotrophic factor
  • Hippocampal neurogenesis
  • Learning and memory

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this