Caloric restriction can improve learning ability in C57/BL mice via regulation of the insulin-PI3K/Akt signaling pathway

Abstract

To identify the molecular mechanism underlying improved spatial learning ability of C57/BL mice on a caloric restricted (CR) diet. Seven-week-old male C57/BL mice were randomly divided into three groups: normal control group (NC group, n = 10), high energy group (n = 10), and low energy group (CR group, n = 10). Body mass and levels of blood glucose were measured every 2 weeks over the course of 30 weeks. After 30 weeks, metabolic parameters, serum total cholesterol, and insulin-like growth factor 1 (IGF-1) were measured, and learning and memory ability of animals were tested using the Morris water maze. The expression of insulin signaling pathway-related proteins in the brain tissues also were tested for molecular mechanism. When compared with the NC group, body weight, and levels of serum glucose decreased in the CR group and increased in the high energy group at all time points tested. Average escape latency and swimming distance were lower in the CR group as compared to the control group after 30 weeks. The serum cholesterol level of the high energy group was significantly higher than that of the control group. The expressions of IGF-1, IR, IRS-1, PI3K, Akt/PKB, and p-CREB protein in the CR group were significantly lower and the expressions of PI3K and Akt/PKB protein in the high energy group were significantly lower than those of the control group at post 30 weeks treatment. Our findings demonstrate that the low energy diet may improve hippocampus-dependent spatial learning ability in C57/BL mice, possibly through a regulatory mechanism of the insulin-PI3K/Akt signaling pathway.

Influence of age-related learning and memory capacity of mice: different effects of a high and low caloric diet

“…Abundant evidence shows that CR increases the life span in several model organisms, ranging from yeast to mice and even primates. Earlier research has demonstrated that CR ameliorates age-related cognitive deficits, consistent with our recent findings [15,40]. CR has been shown to efficiently stimulate autophagy in vivo and in vitro [41].…”

“…Diets were purchased from the Experimental Animal Center of the Academy of Military Medical Sciences. The energy ratio of the diets fed to the NC, CR, and HC groups was 1:0.7:1.3 [15]. Mice were weighed monthly.…”

Insulin resistance and cognitive dysfunction

“…Dementia prevalence is increasing with rapid aging in the population, and MCI as an intervention stage to prevent dementia has become a research hotspot [12,13]. Most recent studies have focused on the role of IR as possible links between diabetes and AD, and the disturbances in brain insulin signaling mechanisms may contribute to the molecular, biochemical, and histopathological lesions in AD [1,14]. Therefore, in this paper, how IR and cognitive impairment are mutually linked and the possible mechanisms are discussed.…”

Systems biology approaches to study the molecular effects of caloric restriction and polyphenols on aging processes

“…In the aging rat brain, CR improved ketone body metabolism and blood flow, often impaired in neurodegenerative disorders . CR also delayed neurodegeneration in aging mice through SIRT1 (Graff et al 2013), improved learning through PI3k/Akt pathway (Ma et al 2014) and was demonstrated to attenuate amyloid b neuropathology in aged mice with Alzheimer's disease (Wang et al 2005). Finally, one of the few investigation conducted in humans showed that a 3-month CR intervention improved memory in the elderly (Witte et al 2009).…”