Aspartate, also known as L-aspartic acid, is an amino acid that plays a dual role in the body, serving as a building block for proteins and functioning as a neurotransmitter within the central nervous system. A neurotransmitter is a chemical messenger that facilitates the transmission of signals between neurons, the specialized cells of the brain. Aspartate’s presence and activity are recognized for their involvement in various neurological processes, contributing to the overall communication network of the brain.
Key Functions in the Brain
Aspartate primarily acts as an excitatory neurotransmitter in the brain, which means it increases the likelihood of a neuron firing an electrical signal. This excitatory nature contributes to its involvement in several complex brain functions, including learning and memory formation. Research suggests that aspartate stimulates N-methyl-D-aspartate (NMDA) receptors, although its binding strength is not as potent as that of glutamate.
The activation of NMDA receptors by aspartate is linked to processes like long-term potentiation (LTP), a persistent strengthening of synapses based on recent activity, which is considered a cellular mechanism underlying learning and memory. Studies have shown that increased levels of D-aspartate, an enantiomer of aspartate, can enhance LTP in hippocampal slices, a brain region crucial for memory. Furthermore, D-aspartate consumption has been shown to promote intermediate-term spatial memory and influence the expression of NMDA receptor subunits in the hippocampus. Beyond learning and memory, aspartate also plays a part in neuronal development, with evidence suggesting its involvement in neuronal differentiation and the maturation of axons.
Aspartate’s Mechanism of Action
Aspartate is a non-essential amino acid, meaning the body can synthesize it as needed within neurons and glial cells in the brain. Its synthesis often involves the transamination of oxaloacetate, a molecule involved in energy metabolism, with glutamate serving as the amino donor. Once synthesized, aspartate is stored in synaptic vesicles within the presynaptic neuron.
Upon the arrival of an electrical signal, aspartate is released into the synaptic cleft, the space between neurons, through a process called exocytosis. After release, aspartate binds to specific receptors on the postsynaptic neuron, primarily NMDA receptors. This binding leads to the opening of ion channels, allowing positively charged ions, including calcium, sodium, and potassium, to flow into the postsynaptic neuron. The influx of calcium ions, in particular, can trigger various intracellular signaling pathways, contributing to the neuron’s response. To terminate its signal and prevent overstimulation, aspartate is removed from the synaptic cleft through reuptake mechanisms or it can be degraded.
Aspartate and Human Health
Aspartate’s functions extend beyond its direct role in learning and memory, influencing various physiological processes and having implications for human health when its regulation is disrupted. As an amino acid, aspartate participates in broader metabolic pathways within the brain, including the malate-aspartate shuttle, which is involved in recycling reducing equivalents between cellular compartments, and contributing to the synthesis of other important molecules like N-acetylaspartate. The concentrations of aspartate in brain cells can vary, with reported values generally ranging from approximately 0.2 to 5 mmol/L.
However, imbalances in aspartate levels, particularly excessive concentrations, can lead to a phenomenon known as excitotoxicity. Excitotoxicity occurs when neurons are overstimulated by excitatory neurotransmitters, leading to an excessive influx of calcium ions into the cell, which can trigger processes that result in neuronal dysfunction and death. This process is implicated in several neurological conditions, including acute injuries like stroke and chronic neurodegenerative diseases such as Alzheimer’s, Huntington’s, and Parkinson’s disease. For instance, in stroke, an acute increase in extracellular glutamate and aspartate can contribute to excitotoxic damage. Similarly, NMDA receptor overactivation, which aspartate can contribute to, is a recognized mechanism in the pathophysiology of various neurodegenerative disorders. Research continues to explore the complex interplay of aspartate in both healthy brain function and its potential contributions to disease states, aiming to identify therapeutic targets.