The effect of insulin and insulin-like growth factors on hippocampus- and amygdala-dependent long-term memory formation

Abstract

Recent work has reported that the insulin-like growth factor 2 (IGF2) promotes memory enhancement. Furthermore, impaired insulin or IGF1 functions have been suggested to play a role in the pathogenesis of neurodegeneration and cognitive impairments, hence implicating the insulin/IGF system as an important target for cognitive enhancement and/or the development of novel treatments against cognitive disorders. Here, we tested the effect of intracerebral injections of IGF1, IGF2, or insulin on memory consolidation and persistence in rats. We found that a bilateral injection of insulin into the dorsal hippocampus transiently enhances hippocampal-dependent memory and an injection of IGF1 has no effect. None of the three peptides injected into the amygdala affected memories critically engaging this region. Together with previous data on IGF2, these results indicate that IGF2 produces the most potent and persistent effect as a memory enhancer on hippocampal-dependent memories. We suggest that the memory-enhancing effects of insulin and IGF2 are likely mediated by distinct mechanisms.

Exogenous insulin-like growth factor 2 administration enhances memory consolidation and persistence in a time-dependent manner

“…In addition, a number of studies have demonstrated the role of IGF2 on the central nervous system (Agis-Balboa et al, 2011;Bracko et al, 2012;Ouchi et al, 2013;Schmeisser et al, 2012;Stern et al, 2014a). Chen et al (2011) reported that hippocampal IGF2 has a critical role in memory consolidation within a limited time window .…”

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

“…Cannulation and injections were carried out as described previously (Chen et al, 2011; Stern et al, 2014b). Rats were anesthetized with ketamine (65 mg/kg)-xylazine (7.5 mg/kg) i.p.…”

“…Inhibitory avoidance training and testing were carried out as described previously (Chen et al, 2011; Stern et al, 2014b). The IA chamber (Med Associates.…”

“…Among these, the expression of insulin-like growth factor 2 (IGF-2 or IGF-II) increases during the first 24 hours following training, and this increase is essential for memory consolidation; in fact, its expression knockdown causes memory impairment (Chen et al, 2011). Furthermore, hippocampal or systemic administration of recombinant IGF-2, but not of another member of the IGF family, IGF-1, significantly enhances the retention and persistence of hippocampal-dependent memories in young adult rats and mice (Chen et al, 2011; Stern et al, 2014a, 2014b), as well as of hippocampal long-term potentiation (Chen et al, 2011). In contrast, IGF-1 may ameliorate memory deficits in aged animals (Markowska et al, 1998; Deak and Sonntag, 2012), suggesting distinct effects and/or mechanisms of IGFs on memory performance and deficit rescuing.…”

Insulin Age-Dependently Modulates Synaptic Transmission and AMPA Receptor Trafficking in Region CA1 of the Rat Hippocampus

“…Over time, the importance of insulin in hippocampal memory and learning processes has become better appreciated [2]- [5]. Although much is known about the behavioral effects of insulin on hippocampal-dependent tasks [6] [7], the molecular effects of insulin in the hippocampus have been largely understudied. In juvenile animals, in vitro field potential recordings have revealed that insulin induces long-term depression (LTD) in various regions of the hippocampus [8]- [11].…”