Diet and cognition: interplay between cell metabolism and neuronal plasticity

Abstract

Purpose of study: To discuss studies in humans and animals revealing the ability of foods to benefit the brain: new information with regards to mechanisms of action and the treatment of neurological and psychiatric disorders.

Recent findings: Dietary factors exert their effects on the brain by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Energy metabolism influences neuronal function, neuronal signaling, and synaptic plasticity, ultimately affecting mental health. Epigenetic regulation of neuronal plasticity appears as an important mechanism by which foods can prolong their effects on long-term neuronal plasticity.

Summary: The prime focus of the discussion is to emphasize the role of cell metabolism as a mediator for the action of foods on the brain. Oxidative stress promotes damage to phospholipids present in the plasma membrane such as the omega-3 fatty acid docosahexenoic acid, disrupting neuronal signaling. Thus, dietary docosahexenoic acid seems crucial for supporting plasma membrane function, interneuronal signaling, and cognition. The dual action of brain-derived neurotrophic factor in neuronal metabolism and synaptic plasticity is crucial for activating signaling cascades under the action of diet and other environmental factors, using mechanisms of epigenetic regulation.

Figure 1

Schematic representation of the actions of diet and exercise on neuronal maintenance and repair. Food and exercise can influence mitochondrial function with resulting effects on synaptic plasticity, and the neural substrates for cognition. The interaction of energy metabolism and synaptic functions is pivotal for the regulation of neuronal function and mental health, and can involve epigenetic modifications. Diet and exercise contributes to build a cognitive reserve for the brain that can be used to support neuronal function and cognition during homeostatic and challenging situations.

Figure 2

(A) The metabolic syndrome can also affect the brain, and disturb energy metabolism and synaptic plasticity. The metabolic syndrome alters the signaling of insulin in nerve cells, which may disturb metabolism and plasticity. Insulin resistance index in groups subjected to n-3 and n-3 deficient diet with or without fructose water. Correlation analysis revealed a positive correlation between (B) serum triglyceride levels and latency time (C) insulin resistance index and latency time on Barnes maze. Values are expressed as mean ± SEM. ^##P<0.01 significant difference from n-3 diet, ^*P<0.05 significant difference from n-3 def/Fru; ANOVA (one-way) followed by Newman–Keuls test. Source: Agrawal & Gomez-Pinilla, 2012 (Ref. 14).

Figure 3

Dietary factors can affect neuronal signaling and energy metabolism. The omega-3 fatty acid docosahexaenoic acid (DHA) can influence neuronal signaling by altering plasma membrane biodynamic or fluidity at synaptic regions (23, 26). DHA is essential for maintaining membrane integrity, which can affect neuronal signaling through receptors embedded in the plasma membrane., i.e., BDNF receptor TrKB activity influences the co-transcriptional regulator PGC-1α via CREB. Such signals can affect mitochondrial energy processing, thereby influencing several aspects of cellular energy metabolism and neuronal plasticity (reviewed in Ref.1). In turn, metabolic activity can also affect membrane homeostasis that supports synaptic plasticity and cognitive function (43). Excessive metabolic activity due to high caloric intake or overexertion results in production of reactive oxygen species (ROS), which promote lipid peroxidation in the cell membrane and the release of aldehydes such as 4HNE that damage cells. The homeostatic interplay between energy management in neurons and its plasticity counterparts appears crucial for the maintenance of neuronal function and neurological health.