TY - JOUR
T1 - Insulin-like growth factor 2 rescues aging-related memory loss in rats
AU - Steinmetz, Adam B.
AU - Johnson, Sarah A.
AU - Iannitelli, Dylan E.
AU - Pollonini, Gabriella
AU - Alberini, Cristina M.
N1 - Funding Information:
This work was supported by National Institute of Mental Health (NIMH) grant R01 MH074736 to Cristina M. Alberini. The authors thank Mark Baxter (Icahn School of Medicine at Mount Sinai) for comments and suggestions. They thank Prof. Richard G. MacDonald, University of Nebraska Medical Center, Omaha, NE, for generously providing an anti-IGF2 receptor antibody.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - Hippocampus
KW - Insulin-like growth factor-2
KW - Memory
KW - Proprotein convertase
KW - Rat
KW - Working memory
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U2 - 10.1016/j.neurobiolaging.2016.04.006
DO - 10.1016/j.neurobiolaging.2016.04.006
M3 - Article
C2 - 27318130
AN - SCOPUS:84968739686
SN - 0197-4580
VL - 44
SP - 9
EP - 21
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -