Intracellular Regulation of Energy and Ions in Glia and Neurons

Introduction of Metabolism Regulation

Metabolism regulation is a complex process relates to membrane transporters and enzymes, then the established networks would support energy dynamics. The human brain is an organ with high energy requirements. The high energy requirement is derived from many neurons and synapses. Glucose is the important energy source for the brain and its absorption and diffusion are regulated by glucose transporters (GLUTs). According to the “Astrocyte-to-Neuron Lactate Shuttle” (ANLS) hypothesis, lactate is almost generated from astrocytes and then transferred to neurons via monocarboxylate transporters (MCTs). Studies have shown that MCT-mediated lactate transport plays important role in multiple physiological processes in the brain.

Fig.1 The astrocyte to neuron lactate shuttle. (Deitmer 2019)

Ions Regulation in Neurons

The electrical potential changes at postsynaptic sites are associated with sustained ion gradients, especially the large Na⁺ gradient maintained by the activity of the Na⁺/K⁺ ATPase. The Na⁺ gradient can further ensure the regulation of other ions, including Ca²⁺, Mg²⁺, H⁺, HCO³⁻, and Cl⁻. A low intracellular Na⁺ concentration is critical for brain functions. Some studies have shown that dysregulation of intracellular Na⁺ is the result of a decreased cellular ATP thereby promoting excitotoxicity.

Fig.2 Scheme illustrating main cellular metabolic pathways and ion transport mechanisms. (Gerkau, 2017)

Modulation of Astrocytic Energy Metabolism and pH

Glycolysis in astrocytes is highly sensitive to neuronal activity. The generation of lactate can be activated by glutamate and K⁺ through different mechanisms. K⁺ is associated with the activity of fast glycolytic in astrocytes and its extracellular clearance is achieved by astrocytes. pH regulation is important for functions in the brain and astrocytes can contribute to pH homeostasis using enzymes, multiple membrane transporters, and H⁺ buffers.

In conclusion, the cooperative processes of neurons and astrocytes can meet the high energy requirements of neurons and ensure the normal operation of brain functions.

Homeostasis Regulation in Glia and Neurons

• Calcium Homeostasis in Glia and Neurons
• Glucose Metabolism in Glia and Neurons
• Glutathione Metabolism in Glia and Neurons
• Ion Homeostasis in Glia and Neurons
• Mitochondrial Function in Nervous System
• Neurotransmitter Release from Neurons and Astrocytes
• pH Regulation in Glia and Neurons
• Cell Volume Regulation of Neurons

Diseases Associated with Homeostasis Disorders

Recent research has shown that homeostasis disorders lead to many different neurological diseases, including neuronal dysfunction, traumatic brain injury, neurodegenerative disorders, and psychiatric disorders. Future research focused on neuronal homeostasis regulation would provide novel therapeutic options for patients with neurological diseases.

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References

1. Deitmer, J.; et al. Energy dynamics in the brain: contributions of astrocytes to metabolism and pH homeostasis. Frontiers in neuroscience. 2019, 13: 1301.
2. Gerkau, N.; et al. Differential effects of energy deprivation on intracellular sodium homeostasis in neurons and astrocytes. Journal of neuroscience research. 2017, 95(11): 2275-2285.