Chia seeds as a potential cognitive booster in the APP23 Alzheimer’s disease model

Abstract

Glucose hypometabolism potentially contributes to Alzheimer’s disease (AD) and might even represent an underlying mechanism. Here, we investigate the relationship of diet-induced metabolic stress and AD as well as the therapeutic potential of chia seeds as a modulator of glucose metabolism in the APP23 mouse model. 4–6 (pre-plaque stage, PRE) and 28–32 (advanced-plaque stage, ADV) weeks old APP23 and wild type mice received pretreatment for 12 weeks with either sucrose-rich (SRD) or control diet, followed by 8 weeks of chia seed supplementation. Although ADV APP23 mice generally showed functioning glucose homeostasis, they were more prone to SRD-induced glucose intolerance. This was accompanied by elevated corticosterone levels and mild insulin insensitivity. Chia seeds improved spatial learning deficits but not impaired cognitive flexibility, potentially mediated by amelioration of glucose tolerance, attenuation of corticosterone levels and reversal of SRD-induced elevation of pro-inflammatory cytokine levels. Since cognitive symptoms and plaque load were not aggravated by SRD-induced metabolic stress, despite enhanced neuroinflammation in the PRE group, we conclude that impairments of glucose metabolism do not represent an underlying mechanism of AD in this mouse model. Nevertheless, chia seeds might provide therapeutic potential in AD as shown by the amelioration of cognitive symptoms.

Chia seeds oil ameliorate chronic immobilization stress-induced neurodisturbance in rat brains via activation of the antioxidant/anti-inflammatory/antiapoptotic signaling pathways

“…This ameliorative impact might be due to the presence of essential fatty acids such as ALA, an essential omega-3 PUFA derived from plants, which has anti-inflammatory and oxidative stress modulators. These findings agreed with the result of Schreyer, et al 67 , who stated that the administration of chia seeds in mice attenuated corticosterone levels in diet-induced metabolic stress and Alzheimer's disease. It also documented that docosahexaenoic acid (DHA)-enriched fish oil, an omega-3 fatty acid, suppressed the increased serum corticosterone concentration in chronically stressed rats 68 .…”

Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis

“…Although APP23 mice do not model AD-related weight loss, their lower body weight at a pre-plaque stage corresponds to lower body weight of AD patients, which arises from early weight loss prior to the onset of clinical AD symptoms [ 16 , 22 ]. Consistent with literature, HSD induced a mild, but HFD a substantial body weight gain [ 19 , 23 – 25 ], in which APP23 mice gained less fat mass. Analysis of food intake as a potential mechanism for lower body weight revealed lower HFD consumption, contradicting a study in APP23 males reporting increased food intake [ 26 ].…”

“…Furthermore, we examined corticosterone as a functional antagonist of insulin and NEFA as a correlate for lipolysis. Corticosterone levels were similar between genotypes as already described [ 19 ], possibly due to young age and low Aβ load of APP23 mice [ 37 ]. NEFA levels were unaltered by genotype but reduced by HFD, potentially due to the lipolysis-inhibiting effect of elevated insulin levels [ 38 ].…”

“…At 0 min, plasma was additionally collected and stored at -80° C for analysis of fasting insulin levels. Terminally, mice were sacrificed as described [ 19 ]. Plasma was stored at -80° C. Tissues were stored partially snap-frozen (-80° C) and partially in 4% PFA/PBS (4° C).…”

“…Here, we investigate early AD-related metabolism and body weight changes challenging the APP-overexpressing APP23 mouse model [ 19 ] with different diets before Aβ-plaque development to extensively characterize its metabolic features and the impact of different fuel sources. Thereby, we aim to gain insights into underlying mechanisms of AD-related metabolic and body weight changes, which might provide valuable information for early diagnosis or therapeutic approaches.…”