1. Lactate's behavioral switch in the brain: An in-silico model.
- Author
-
Soltanzadeh, Milad, Blanchard, Solenna, Soucy, Jean-Paul, and Benali, Habib
- Subjects
- *
LACTATES , *CAPILLARIES , *ORDINARY differential equations , *LACTATION , *BLOOD lactate , *BRAIN injuries - Abstract
• Blood lactate does not strongly contribute to the initial dip in neuronal lactate. • Astrocyte-neuron lactate shuttle conditionally provides lactate to the neurons. • Existence and strength of lactate shuttle depends on transporter properties. • Lactate shuttling also depends on the astrocytic lactate production. Emerging evidence emphasizes lactate's involvement in both physiological processes (energy metabolism, memory, etc.) and disease (traumatic brain injury, epilepsy, etc.). Furthermore, the usefulness of mathematical modeling in deciphering underlying dynamics of the brain to investigate lactate roles and mechanisms of action has been well established. Here, we analyze a novel mathematical model of brain lactate exchanges between four compartments: neurons, astrocytes, capillaries, and extracellular space. A system of four ordinary differential equations is proposed to explain interactions between these compartments. We first optimize and analyze the model's parameters under normal, resting state conditions, and then use it to simulate changes linked to elevated arterial lactate. Our results show that even though increased arterial lactate results in increased uptake by astrocytes and release to the extracellular space, it cannot strongly recover the initial drop in neuronal lactate concentration. Also, we show that the direction of lactate transport between the compartments is influenced by the maximum astrocyte production rate and the transport rate between astrocytes and extracellular space. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF