Neurodevelopmental Disorders: Effect of High-Fat Diet on Synaptic Plasticity and Mitochondrial Functions

Abstract

Neurodevelopmental disorders (NDDs) include diverse neuropathologies characterized by abnormal brain development leading to impaired cognition, communication and social skills. A common feature of NDDs is defective synaptic plasticity, but the underlying molecular mechanisms are only partially known. Several studies have indicated that people’s lifestyles such as diet pattern and physical exercise have significant influence on synaptic plasticity of the brain. Indeed, it has been reported that a high-fat diet (HFD, with 30–50% fat content), which leads to systemic low-grade inflammation, has also a detrimental effect on synaptic efficiency. Interestingly, metabolic alterations associated with obesity in pregnant woman may represent a risk factor for NDDs in the offspring. In this review, we have discussed the potential molecular mechanisms linking the HFD-induced metabolic dysfunctions to altered synaptic plasticity underlying NDDs, with a special emphasis on the roles played by synaptic protein synthesis and mitochondrial functions.

JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function

“…Data from the array allowed us to raise several points: (1) Chronic HFD feeding caused disruption in energetic metabolic pathways. This would be in accordance with previous reports in the field in which HFD has been demonstrated to disrupt physiological metabolism and promote insulin resistance, as well as obesity and other pathological alterations (Tsan et al 2021 ; Leigh and Morris 2020 ; Penna et al 2020 ). Increased ingestion of fats, obesity and resistance to hormones like insulin caused disturbances in normal cognitive function and structures as reported by our research team and others (Tsan et al 2021 ; Leigh and Morris 2020 ; Penna et al 2020 ).…”

Behavioral, Anti-Inflammatory, and Neuroprotective Effects of a Novel FPR2 Agonist in Two Mouse Models of Autism

“…It is noteworthy that, due to the bidirectional communication between the immune system and the brain [13], cytokine levels are able to modulate neuronal function and behavioral processes [14]. Moreover, multiple lines of evidence from genetic linkage studies on animal models have highlighted aberrant brain plasticity in the pathophysiology of ASD, including altered neurogenesis, neurite outgrowth, synaptogenesis, and synaptic plasticity [15][16][17]. In this scenario, a key role is played by the hippocampus, a brain region where active neurogenesis and long-term changes of synaptic strength take place [18,19].…”

The Mechanism of Fos and Leptin Receptor in Neural Tube Development of Offspring Under The Regulation of Energy Balance

“…This result indicates that a high-fat diet can affect embryonic development. Studies have shown that long-term high-fat diets can cause mitochondrial dysfunction and affect the offspring's synapses development [23]. When the embryos of the three groups continued to develop to 12.5d and 14.5d, it was observed that the cells in the neural tube of the Mex3c group and the HFD group were small and scarce.…”

“…Long-term high-fat diet can cause lipid deposition, increase fat, break the balance of human lipid metabolism, and induce non-alcoholic fatty liver. Studies have shown that long-term high-fat diet during pregnancy can affect offspring neurites by damaging mitochondrial function [13]; that a high-fat diet can lead to changes in mitochondrial function, which in turn leads to lipid metabolism disorders and neurodevelopment. Professor Lu of the research group has proved in previous experiments that Mex3c gene-de cient mice induce the body to form a negative energy state [14] and other studies have shown that without inhibiting food intake, Mex3c mutations can contribute to glucose and lipid metabolism, resulting in decreased blood glucose and blood lipid concentrations in mice, and increased insulin effect, making Mex3c resistant to obesity caused by food [15,16].…”