Insulin-like growth factor 2 rescues aging-related memory loss in rats

Neurobiol Aging. 2016 Aug;44:9-21. doi: 10.1016/j.neurobiolaging.2016.04.006. Epub 2016 Apr 21.


Aging is accompanied by declines in memory performance, and particularly affects memories that rely on hippocampal-cortical systems, such as episodic and explicit. With aged populations significantly increasing, the need for preventing or rescuing memory deficits is pressing. However, effective treatments are lacking. Here, we show that the level of the mature form of insulin-like growth factor 2 (IGF-2), a peptide regulated in the hippocampus by learning, required for memory consolidation and a promoter of memory enhancement in young adult rodents, is significantly reduced in hippocampal synapses of aged rats. By contrast, the hippocampal level of the immature form proIGF-2 is increased, suggesting an aging-related deficit in IGF-2 processing. In agreement, aged compared to young adult rats are deficient in the activity of proprotein convertase 2, an enzyme that likely mediates IGF-2 posttranslational processing. Hippocampal administration of the recombinant, mature form of IGF-2 rescues hippocampal-dependent memory deficits and working memory impairment in aged rats. Thus, IGF-2 may represent a novel therapeutic avenue for preventing or reversing aging-related cognitive impairments.

Keywords: Hippocampus; Insulin-like growth factor-2; Memory; Proprotein convertase; Rat; Working memory.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / psychology*
  • Animals
  • Hippocampus / metabolism
  • Insulin-Like Growth Factor II / administration & dosage*
  • Insulin-Like Growth Factor II / deficiency
  • Insulin-Like Growth Factor II / metabolism
  • Insulin-Like Growth Factor II / physiology*
  • Male
  • Memory Disorders / etiology*
  • Memory Disorders / prevention & control*
  • Memory*
  • Memory, Short-Term
  • Molecular Targeted Therapy
  • Proprotein Convertase 2 / metabolism
  • Protein Processing, Post-Translational
  • Rats
  • Rats, Inbred F344
  • Recombinant Proteins / administration & dosage


  • Recombinant Proteins
  • Insulin-Like Growth Factor II
  • Proprotein Convertase 2