Energetic substrate availability regulates synchronous activity in an excitatory neural network.

Neural networks are required to meet significant metabolic demands associated with performing sophisticated computational tasks in the brain. The necessity for efficient transmission of information imposes stringent constraints on the metabolic pathways that can be used for energy generation at the synapse, and thus low availability of energetic substrates can reduce the efficacy of synaptic function. Here we study the effects of energetic substrate availability on global neural network behavior and find that glucose alone can sustain excitatory neurotransmission required to generate high-frequency synchronous bursting that emerges in culture. In contrast, obligatory oxidative energetic substrates such as lactate and pyruvate are unable to substitute for glucose, indicating that processes involving glucose metabolism form the primary energy-generating pathways supporting coordinated network activity. Our experimental results are discussed in the context of the role that metabolism plays in supporting the performance of individual synapses, including the relative contributions from postsynaptic responses, astrocytes, and presynaptic vesicle cycling. We propose a simple computational model for our excitatory cultures that accurately captures the inability of metabolically compromised synapses to sustain synchronous bursting when extracellular glucose is depleted.

Modulation of lipid metabolism in glycyrrhizic acid-treated rats fed on a high-calorie diet and exposed to short or long-term stress.

Stress and high-calorie diets increase the risk of developing metabolic syndrome. Glycyrrhizic acid (GA) has been shown to improve dyslipidaemia in rats fed on a high-calorie diet. This study aimed to examine the effects of GA on lipid metabolism in rats exposed to short- or long-term stress and on a high-calorie diet. The parameters examined included serum lipid profiles, serum free fatty acids and fatty acid profiles in tissues, and expression of peroxisome proliferator-activated receptors (PPAR), lipoprotein lipase (LPL), elongases and desaturases. Within the 14- or 28-day exposure groups, neither stress nor GA affected the lipid profile and serum free fatty acids. Stress did not affect PPAR-α expression in both the 14- and 28-day exposure groups. However, GA-treated rats from the former group had increased PPAR-α expression only in the kidney while all other tissues from the latter group were unaffected. Stress increased PPAR-γ expression in the heart of the 28-day exposure group but its expression was unaffected in all tissues of the 14-day exposure group. GA elevated PPAR-γ expression in the kidney and the skeletal muscles. Neither stress nor GA affected LPL expressions in all tissues from the 14-day exposure group but its expressions were elevated in the QF of the stressed rats and heart of the GA-treated rats of the 28-day exposure group. As for the elongases and desaturases in the liver, stress down-regulated ELOVL5 in the long-term exposure group while up-regulated ELOVL6 in the short-term exposure group while hepatic desaturases were unaffected by stress. Neither elongase nor desaturase expressions in the liver were affected by GA. This research is the first report of GA on lipid metabolism under stress and high-calorie diet conditions and the results gives evidence for the role of GA in ameliorating MetS via site-specific regulation of lipid metabolism gene expressions and modification of fatty acids.