Dietary restriction in cerebral bioenergetics and redox state

Abstract

The brain has a central role in the regulation of energy stability of the organism. It is the organ with the highest energetic demands, the most susceptible to energy deficits, and is responsible for coordinating behavioral and physiological responses related to food foraging and intake. Dietary interventions have been shown to be a very effective means to extend lifespan and delay the appearance of age-related pathological conditions, notably those associated with brain functional decline. The present review focuses on the effects of these interventions on brain metabolism and cerebral redox state, and summarizes the current literature dealing with dietary interventions on brain pathology.

Keywords: AD, Alzheimer's disease; CR, caloric restriction; Caloric restriction; Energy metabolism; FR, food restriction; IF, intermittent fasting; KA, kainic acid; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Mitochondria; NOS, nitric oxide synthase; Neurological diseases; PD, Parkinson's disease; PTZ, pentylenetetrazole; ROS, reactive oxygen species; TCA, tricarboxylic acid cycle.

Fig. 1

The brain as a master regulator of body energy control. The figure represents a simplified scheme of how the brain receives signals from peripheral tissues in the hypothalamus. Orexigenic (AgRP/NPY) and anorexigenic (POMC/CART) neurons in the arcuate nucleus (ARC) of the hypothalamus sense these and other cues, such as circulating blood glucose levels. These signals are further integrated by interaction with other hypothalamic nuclei (LH—lateral hypothalamus; PVN—paraventricular nucleus) and finally project into the areas of the brain involved in the reward system, including the ventral tegmental area (VTA) and the nucleus accumbens in the striatum.

Fig. 2

Glucose use in the brain. Glucose is used for multiple functions in the brain. Glycolysis followed by oxidation of acetyl-CoA in the TCA cycle provides reduced equivalents that can be used by mitochondria to synthesize ATP. Alternatively, oxidation through the pentose phosphate pathway provides NADPH, required for the reduction of glutathione, a central anti-oxidant in the brain. Glucose is also required as a precursor to synthesize neurotransmitters, and can be stored to some extent in astrocytes in the form of glycogen. In the absence of glucose, ketone bodies produced in the liver can cross the blood–brain barrier and partially replace glucose as an energy source.

Fig. 3

Effects of CR, FR and IF on some neurodegenerative conditions. The sizes of the rectangles represent the relative number of publications for each pathology (numbers are in parenthesis), summarized from the following: Anson et al. , Armentero et al. , Arumugam et al. , Azarbar et al. , Bhattacharya et al. , Bough et al. , Bough et al. , Bruce-Keller et al. , Contestabile et al. , Costantini et al. , Dhurandar et al. , Duan and Mattson , Duan et al. , Eagles et al. , Greene et al. , Griffioen et al. , Halagappa et al. , Hamadeh and Tarnopolsky , Hamadeh et al. , Hartman et al. , Holmer et al. , Kumar et al. , Lee et al. [58], Liu et al. , Mantis et al. , Mouton et al. , Parinejad et al. , Patel et al. , Patel et al. , Pedersen and Mattson , Qin et al. , Qin et al. , Qiu et al. , Wang et al. , Wu et al. , Yoon et al. , Yu and Mattson , Zhu et al. .