Characterization of Monocarboxylate Transporters in the Brain of the Hooded Seal (Cystophora cristata) Reveal Possible Biochemical Adaptation to Diving

Abstract

Diving mammals are perpetually required to manage low-oxygen conditions throughout their lives. The mammalian brain is an organ particularly vulnerable to low oxygen levels due to its high energy demands, which require steady aerobic ATP production. The brain of the deep- diving hooded seal (Cystophora cristata) demonstrates remarkable tolerance to hypoxia. Studies suggest that this brain hypoxia tolerance may be attributed to different metabolic roles of astrocytes and neurons compared to what is typically observed in non-diving mammals, as formulated in the hypothesis of a reversed astrocyte-neuron lactate shuttle (ANLS) in the brains of seals. Monocarboxylate transporters (MCTs) mediate the transport of lactate (and other monocarboxylates) across cell membranes. In the mammalian central nervous system, MCT1, MCT2 and MCT4 are the prominent subtypes, each with distinct properties that influence their roles in lactate transport. MCT4 is an efficient lactate exporter, MCT2 is an efficient lactate importer, and MCT1 mediates both efficient import and export of lactate. Neurons and astrocytes in non-diving mammals exhibit distinct MCT subtypes reflecting lactate efflux from astrocytes and lactate influx into neurons, according to the ANLS concept. In this study, the distribution of MCTs in the hooded seal brain was investigated to gain further insights into the metabolic roles of astrocytes and neurons that may underly the brain hypoxia tolerance in this species. The visual cortex from both hooded seals and mice was immunolabelled for astrocytes, neurons, MCT1, MCT2, and MCT4, and examined under a fluorescence microscope to reveal cell-specific MCT distribution patterns in the two cell types. The MCT4 antibody was the only one among the MCT antibodies to produce a specific signal in the tissues. Hooded seal neurons exhibited similar proportions of MCT4 in neurons and astrocytes, whereas mice showed significantly higher proportions of MCT4 in astrocytes compared to neurons, as expected. Hooded seal neurons exhibited significantly higher proportions of MCT4 compared to mice neurons. These data suggest that hooded seal neurons may possess an enhanced capacity for lactate efflux, potentially reflecting a greater ability to sustain anaerobic glycolysis, which presumably becomes increasingly important for maintaining energy metabolism during prolonged dives. These findings offer new insights into the molecular properties that may underpin the remarkable brain hypoxia tolerance of hooded seals.