Biology subjects

Pierre, C.

Publications and source records attributed to Pierre, C..

3 recordsLinked to original sources

bioRxiv2022

The enzymatic and neurochemical outcomes of a mutation in Mexican cavefish MAO reveal teleost-specific aspects of brain monoamine homeostasis

Monoamine oxidases (MAO; MAO-A and MAO-B in mammals) are enzymes catalyzing the degradation of biogenic amines, including monoamine neurotransmitters. In humans, coding mutations in MAOs are extremely rare and deleterious. Here, we assessed the structural and biochemical consequences of a point mutation (P106L) in the single mao gene of the blind cavefish Astyanax mexicanus. This mutation decreased mao enzymatic activity by ~3-fold, probably as a result of decreased flexibility in one of the three loops forming the entrance of the active site, thus reducing the access of substrates. HPLC measurements in brains of mutant and non-mutant larvae and adults of the cave and surface morphs of the species showed major disturbances in serotonin, dopamine and noradrenalin (and metabolites) contents in mutants, demonstrating that the P106L mao mutation is fully responsible for monoaminergic disequilibrium in the P106L mao mutant cavefish brain. The outcomes of the mutation were different in the posterior brain (containing the raphe nucleus) and the anterior brain (containing fish-specific hypothalamic serotonergic clusters), revealing contrasting properties in neurotransmitter homeostasis in these different neuronal groups. We also discovered that the effects of the mutation were partially compensated by a decrease in activity of the tph, the serotonin biosynthesis rate-limiting enzyme. Finally, the neurochemical outcomes of the mao P106L mutation differed in many respects from a treatment with deprenyl, an irreversible MAO inhibitor, showing that genetic and pharmacological interference with MAO function are not the same. Our results shade light on our understanding of cavefish evolution, on the specificities of fish monoaminergic systems, and on MAO-dependent homeostasis of brain neurochemistry in general.

neuroscience↗

bioRxiv2022

Trim33 conditions the lifespan of primitive macrophages and onset of definitive macrophage production

TRIM33 (Tif1-{gamma}) is a transcriptional regulator notably involved in several aspects of hematopoiesis. It is essential for the production of erythrocytes in zebrafish, and for the proper functionning and aging of hematopoietic stem and progenitor cells (HSPCs) in mice. Here we have found that in zebrafish development, Trim33 is essential cell-autonomously for the lifespan of the yolk sac derived primitive macrophages, as well as for the initial production of definitive (HSPC-derived) macrophages in the first niche of definitive hematopoiesis, the caudal hematopoietic tissue. Moreover, Trim33 deficiency leads to an excess production of definitive neutrophils and thrombocytes. Our data indicate that Trim33 radically conditions the differentiation ouput of aorta-derived HSPCs in all four erythro-myeloid cell types, in a niche-specific manner.

developmental biology↗

bioRxiv2020

A mutation in monoamine oxidase (MAO) affects the evolution of stress behavior in the blind cavefish Astyanax mexicanus

The neurotransmitter serotonin controls a great variety of physiological and behavioral processes. In humans, mutations affecting the monoamine oxidase or MAO, the serotonin-degrading enzyme, are highly deleterious. Yet, blind cavefish of the species A. mexicanus carry a partial loss-of-function mutation in MAO (P106L) and seem to thrive in their subterranean environment. Here, we established 4 fish lines, corresponding to the blind cave-dwelling and the sighted river-dwelling morphs of this species, with or without the mutation, in order to decipher the exact contribution of mao P106L in the evolution of cavefish neuro-behavioral traits. Unexpectedly, although mao P106L appeared as an excellent candidate for the genetic determinism of the loss of aggressive and schooling behaviors in cavefish, we demonstrated that it was not the case. Similarly, the anatomical variations in monoaminergic systems observed between cavefish and surface fish brains were independent from mao P106L, and rather due other, morph-dependent developmental processes. On the other hand, we found that mao P106L strongly affected anxiety-like behaviors. Cortisol measurements showed lower basal levels and an increased amplitude of stress response after a change of environment in fish carrying the mutation. Finally, we studied the distribution of the P106L mao allele in wild populations of cave and river A. mexicanus, and discovered that the mutant allele was present - and sometimes fixed - in all populations inhabiting caves of the Sierra de El Abra. The possibility that this partial loss-of-function mao allele evolves under a selective or a genetic drift regime in the particular cave environment is discussed.

neuroscience↗