Dietary Reversal Ameliorates Short- and Long-Term Memory Deficits Induced by High-fat Diet Early in Life

Abstract

A high-fat diet (HFD), one of the major factors contributing to metabolic syndrome, which is associated with an increased risk of neurodegenerative diseases, leads to insulin resistance and cognitive impairment. It is not known whether these alterations are improved with dietary intervention. To investigate the long-term impact of a HFD on hippocampal insulin signaling and memory, C57BL6 mice were placed into one of three groups based on the diet: a standard diet (control), a HFD, or a HFD for 16 weeks and then the standard diet for 8 weeks (HF16). HFD-induced impairments in glucose tolerance and hippocampal insulin signaling occurred concurrently with deficits in both short- and long-term memory. Furthermore, these conditions were improved with dietary intervention; however, the HFD-induced decrease in insulin receptor expression in the hippocampus was not altered with dietary intervention. Our results demonstrate that memory deficits due to the consumption of a HFD at an early age are reversible.

Long‐term Phase 1/2 intraspinal stem cell transplantation outcomes in ALS

“…Nevertheless, similar to our prior analysis,16 to gain insight into potential benefit and plan for a future trial, participants from the Pooled Resource Open‐Access ALS Clinical Trials (PRO‐ACT) dataset18, 19 and the ceftriaxone trial (dataset provided by the Northeast ALS Consortium)20 served as historical controls. The PRO‐ACT dataset contains open‐access ALS Functional Rating Scale revised (ALSFRS‐R) and survival data for over 10,723 participants from 23 Phase 2 and 3 ALS trials conducted between 1990 and 2013, including the ceftriaxone cohort 18, 19, 21. The large data volume collected under controlled environments justifies its use as a noncontemporaneous historical dataset.…”

“…HSSC Ph1/2 were open-label feasibility/safety studies without a control population and were not powered to demonstrate efficacy. Nevertheless, similar to our prior analysis, 16 to gain insight into potential benefit and plan for a future trial, participants from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) dataset 18,19 and the ceftriaxone trial (dataset provided by the Northeast ALS Consortium) 20 served as historical controls. The PRO-ACT dataset contains open-access ALS Functional Rating Scale revised (ALSFRS-R) and survival data for over 10,723 participants from 23 Phase 2 and 3 ALS trials conducted between 1990 and 2013, including the ceftriaxone cohort.…”

“…The PRO-ACT dataset contains open-access ALS Functional Rating Scale revised (ALSFRS-R) and survival data for over 10,723 participants from 23 Phase 2 and 3 ALS trials conducted between 1990 and 2013, including the ceftriaxone cohort. 18,19,21 The large data volume collected under controlled environments justifies its use as a noncontemporaneous historical dataset. PRO-ACT participants were included only if they contained data on age, gender, disease duration, and an ALSFRS-R score within 1 month of when records were first available to use as a baseline.…”

Neurological consequences of obesity

“…108 Finally, animal studies support the findings in man and also demonstrate that resolving obesity improves cognitive performance. 109–111 Switching mice from a HFD to a regular diet to reduce caloric intake results in improved metabolic health, with increased insulin sensitivity and improvement in cognitive function. These improvements are associated with reduced blood brain barrier-leakage, decreased glial activation, and increased vascular perfusion.…”

“…These improvements are associated with reduced blood brain barrier-leakage, decreased glial activation, and increased vascular perfusion. 109–111 …”