Effects of high-fat diet on nutrient metabolism and cognitive functions in young APPKINL-G-F/NL-G-F mice.

AIM: Type 2 diabetes mellitus (T2DM) is an increased risk factor for Alzheimer's disease (AD); however, the relationship between the 2 conditions is controversial. High-fat diet (HFD) causes cognitive impairment with/without Aß accumulation in middle-aged or aged transgenic (Tg) and knock-in (KI) AD mouse models, except for metabolic disorders, which commonly occur in all mice types. Alternatively, whether HFD in early life has an impact on nutrient metabolism and neurological phenotypes in young AD mouse models is not known. In the present study, we examined the effects of HFD on young APPKINL-G-F/NL-G-F mice, one of the novel KI-AD mouse models. METHODS: The mice were categorized by diet into 2 experimental groups, normal diet (ND) and HFD. Four-week-old wild-type (WT) and APPKINL-G-F/NL-G-F mice were fed ND or HFD for 9 weeks. Both types of mice on ND and HFD were examined during young adulthood. RESULTS: HFD caused T2DM-related metabolic disturbances in both young WT and APPKINL-G-F/NL-G-F mice, whereas impaired thermoregulation and shortage of alternative energy sources specifically occurred in young APPKINL-G-F/NL-G-F mice. However, HFD had no impact on the cognitive function, Aß levels, and phosphorylation of hippocampal insulin receptor substrate 1 (IRS1) at all the 3 Ser sites in both types of mice. CONCLUSION: HFD is effective in causing metabolic disturbances in young WT and APPKINL-G-F/NL-G-F mice but is ineffective in inducing neurological disorders in both types of mice, suggesting that the aging effects, along with long-term HFD, facilitate neurological alterations.

Dietary magnesium deficiency induces the expression of neuroinflammation-related genes in mouse brain.

AIMS: Dietary Mg2+ deficiency (MgD) impairs hippocampus-dependent memory in mice; however, the molecular mechanisms underlying MgD-induced memory impairments are unclear. Here, we investigated the molecular signatures in the hippocampus of MgD mice by analyzing the hippocampal transcriptome. METHODS: We performed RNA-sequencing of the hippocampal transcriptome of MgD mice. We used gene ontology analyses and quantitative real-time PCR to validate the RNA-sequencing results. RESULTS: mRNAs for neuroinflammation-related genes were upregulated in the hippocampus and cortex of MgD mice. CONCLUSION: MgD induces neuroinflammation in the mouse brain, including the hippocampus and cortex. Our findings suggest that MgD-induced neuroinflammation triggers the impairments of hippocampus-dependent memory.

Dietary magnesium deficiency impairs hippocampus-dependent memories without changes in the spine density and morphology of hippocampal neurons in mice.

Magnesium (Mg2+) is an essential mineral for maintaining biological functions. One major action of Mg2+ in the brain is modulating the voltage-dependent blockade of N-methyl-d-aspartate type glutamate receptors, thereby controlling their opening, which is crucial for synaptic plasticity. Therefore, Mg2+ has been shown to play critical roles in learning and memory, and synaptic plasticity. However, the effects of dietary Mg2+ deficiency (MgD) on learning and memory and the morphology of neurons contributing to memory performance have not been examined in depth. Here, we show that MgD impairs hippocampus-dependent memories in mice. Mice fed an MgD diet showed deficits in hippocampus-dependent contextual fear, spatial and social recognition memories, although they showed normal amygdala- and insular cortex-dependent conditioned taste aversion memory, locomotor activity, and emotional behaviors such as anxiety-related and social behaviors. However, MgD mice showed normal spine density and morphology of hippocampal neurons. These findings suggest that MgD impairs hippocampus-dependent memory without affecting the morphology of hippocampal neurons.