When the brain goes diving: transcriptome analysis reveals a reduced aerobic energy metabolism and increased stress proteins in the seal brain

Abstract

BackgroundDuring long dives, the brain of whales and seals experiences a reduced supply of oxygen (hypoxia). The brain neurons of the hooded seal (Cystophora cristata) are more tolerant towards low-oxygen conditions than those of mice, and also better survive other hypoxia-related stress conditions like a reduction in glucose supply and high concentrations of lactate. Little is known about the molecular mechanisms that support the hypoxia tolerance of the diving brain.ResultsHere we employed RNA-seq to approach the molecular basis of the unusual stress tolerance of the seal brain. An Illumina-generated transcriptome of the visual cortex of the hooded seal was compared with that of the ferret (Mustela putorius furo), which served as a terrestrial relative. Gene ontology analyses showed a significant enrichment of transcripts related to translation and aerobic energy production in the ferret but not in the seal brain. Clusterin, an extracellular chaperone, is the most highly expressed gene in the seal brain and fourfold higher than in the ferret or any other mammalian brain transcriptome. The largest difference was found for S100B, a calcium-binding stress protein with pleiotropic function, which was 38-fold enriched in the seal brain. Notably, significant enrichment of S100B mRNA was also found in the transcriptomes of whale brains, but not in the brains of terrestrial mammals.ConclusionComparative transcriptomics indicates a lower aerobic capacity of the seal brain, which may be interpreted as a general energy saving strategy. Elevated expression of stress-related genes, such as clusterin and S100B, possibly contributes to the remarkable hypoxia tolerance of the brain of the hooded seal. Moreover, high levels of S100B that possibly protect the brain appear to be the result of the convergent adaptation of diving mammals.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2892-y) contains supplementary material, which is available to authorized users.

Brain transcriptomes of harbor seals demonstrate gene expression patterns of animals undergoing a metabolic disease and a viral infection

“…In marine mammals, transcriptomics has never been used to comprehend the cause of an unknown disease and rarely has it been used to characterize the global gene expression of known marine mammal stressors (Mancia et al, 2014; Niimi et al, 2014; Khudyakov et al, 2015a; Khudyakov et al, 2015b; Fabrizius et al, 2016). Here, we used transcriptomics to compare gene expression patterns to known and unknown disease states of stranded harbor seals.…”

“…There has been some increase in marine mammal transcriptomic studies, such as a study by Hoffman et al (2013) which suggested that post-mortem samples can be reliable resources for genomic studies. Yet, there have been few studied that use transcriptomics to measure physiological stress responses in marine mammals, and there have been no studies that looked at pathogen responses in these megafauna (Mancia et al, 2014; Niimi et al, 2014; Khudyakov et al, 2015a; Khudyakov et al, 2015b; Fabrizius et al, 2016). …”

Transcriptome Analysis Identifies Key Metabolic Changes in the Hooded Seal (Cystophora cristata) Brain in Response to Hypoxia and Reoxygenation

“…5399 and 7247) and by the authorities at the University of Tromsø (permit numbers: AAB/06). To minimize the use of animals, the tissues were employed in multiple studies [26, 29, 30, 34]. …”

“…The first assembly was generated using only the 300 nt long trimmed paired-end reads (12,473,522 reads) from seal visual cortex [30]. The second assembly was generated using, in addition, all the 150 nt paired-end reads from the hypoxia treated samples (312,047,506 reads).…”

“…The hypoxia tolerance of the neurons of the hooded seal brain is accompanied by the unusual localization of neuroglobin, cytochrome c and lactate dehydrogenase b in the astrocytes rather than the neurons [27–29], which indicates a higher aerobic capacity of glia cells and thus a lower dependence of neurons on O 2 . A recent comparative transcriptome approach suggested a lower aerobic energy metabolism in the seal brain compared to that of the ferret ( Mustela putorius furo ) and indicated that the stress-proteins clusterin and S100B may contribute to the hypoxia tolerance of the brain of diving mammals [30]. …”