Resources
Authors & Affiliations
Tommaso Dalla Tor, Paula Sotres Gomez, Astrid Cannich, Filippo Drago, Ignacio Fernández-Moncada, Giovanni Marsicano
Abstract
The brain is one of the most active metabolic organs. Indeed, weighing 2% of total body weight, it consumes up to 20% of the energy. Most of the brain energy comes from glucose catabolism, resulting in the production of ATP and lactate. Brain lactate is mainly produced by astrocytes through a process called aerobic glycolysis, while neurons, being high oxidative cells, preferentially use mitochondrial respiration to produce ATP. In this frame, astrocytes provide lactate to neurons, in a process called astrocytes to neurons lactate shuttle. Lactate is not only important as a metabolic support in the brain, but it is also a fundamental signaling molecule. The mechanisms regulating lactate production and release in the brain are, however, scantly known. Cannabinoid receptors type 1 (CB1R) has recently emerged as an important factor playing a complex role in these processes. Whereas persistent (24h) activation of astroglial CB1R leads to a reduction of lactate, recent unpublished data from our laboratory showed that their transient stimulation (5 min) triggers an increase of lactate levels. These data, however, were obtained mainly in cultured astrocytes, and the impact of CB1R activity on lactate levels in vivo has never been directly measured. Here, using a novel lactate fluorescent biosensor (eLacco2.1) and fiber photometry, we demonstrate the possibility to measure lactate levels in freely moving animals. Interestingly, we observed that lactate levels are regulated by cannabinoid administration and locomotor activity. Current experiments aim at addressing the potential relationship between locomotor effects of cannabinoids and lactate regulation.