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

Adam B. Steinmetz, Sarah A. Johnson, Dylan E. Iannitelli, Gabriella Pollonini, Cristina Alberini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9-21
Number of pages13
JournalNeurobiology of Aging
Volume44
DOIs
StatePublished - Aug 1 2016

Fingerprint

Memory Disorders
Somatomedins
Young Adult
Proprotein Convertase 2
Short-Term Memory
Synapses
Rodentia
Hippocampus
Learning
Peptides
Enzymes
Therapeutics
Population

Keywords

  • Hippocampus
  • Insulin-like growth factor-2
  • Memory
  • Proprotein convertase
  • Rat
  • Working memory

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Insulin-like growth factor 2 rescues aging-related memory loss in rats. / Steinmetz, Adam B.; Johnson, Sarah A.; Iannitelli, Dylan E.; Pollonini, Gabriella; Alberini, Cristina.

In: Neurobiology of Aging, Vol. 44, 01.08.2016, p. 9-21.

Research output: Contribution to journalArticle

Steinmetz, Adam B. ; Johnson, Sarah A. ; Iannitelli, Dylan E. ; Pollonini, Gabriella ; Alberini, Cristina. / Insulin-like growth factor 2 rescues aging-related memory loss in rats. In: Neurobiology of Aging. 2016 ; Vol. 44. pp. 9-21.
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