Selenoprotein T Deficiency Leads to Neurodevelopmental Abnormalities and Hyperactive Behavior in Mice.
Selenoprotein T (SelT) is a newly discovered thioredoxin-like protein, which is abundantly but transiently expressed in the neural lineage during brain ontogenesis. Because its physiological function in the brain remains unknown, we developed a conditional knockout mouse line (Nes-Cre/SelTfl/fl) in which SelT gene is specifically disrupted in nerve cells. At postnatal day 7 (P7), these mice exhibited reduced volume of different brain structures, including hippocampus, cerebellum, and cerebral cortex. This phenotype, which is observed early during the first postnatal week, culminated at P7 and was associated with increased loss of immature neurons but not glial cells, through apoptotic cell death. This phenomenon was accompanied by elevated levels of intracellular reactive oxygen species, which may explain the increased neuron demise and reduced brain structure volumes. At the second postnatal week, an increase in neurogenesis was observed in the cerebellum of Nes-Cre/SelTfl/flmice, suggesting the occurrence of developmental compensatory mechanisms in the brain. In fact, the brain volume alterations observed at P7 were attenuated in adult mice. Nevertheless, SelT mutant mice exhibited a hyperactive behavior, suggesting that despite an apparent morphological compensation, SelT deficiency leads to cerebral malfunction in adulthood. Altogether, these results demonstrate that SelT exerts a neuroprotective role which is essential during brain development, and that its loss impairs mice behavior.
Inserm, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, Normandy University, Mont-Saint-Aignan, 76821, France.
Matthieu T
MT
Castex
Sciences Faculty, University of Rouen, 76821, Mont-Saint-Aignan, France.
Arnaud
A
Arabo
PRIMACEN, Institute for Research and Innovation in Biomedicine, University of Rouen, 76821, Mont-Saint-Aignan, France.
Magalie
M
Bénard
PSY-NCA, EA4700, University of Rouen, 76821, Mont-Saint-Aignan, France.
Vincent
V
Roy
Inserm, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, Normandy University, Mont-Saint-Aignan, 76821, France.
Vadim
V
Le Joncour
Inserm, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, Normandy University, Mont-Saint-Aignan, 76821, France.
Gaëtan
G
Prévost
Inserm, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, Normandy University, Mont-Saint-Aignan, 76821, France.
Jean-Jacques
JJ
Bonnet
Inserm, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, Normandy University, Mont-Saint-Aignan, 76821, France. youssef.anouar@univ-rouen.fr.
Youssef
Y
Anouar
Inserm, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, Normandy University, Mont-Saint-Aignan, 76821, France.
Anthony
A
Falluel-Morel
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D006706:Homeostasis; D006948:Hyperkinesis / Q000378:metabolism* / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009420:Nervous System / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D009421:Nervous System Malformations / Q000378:metabolism* / Q000473:pathology; D064231:Nestin / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D010084:Oxidation-Reduction; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051140:Selenoproteins / Q000172:deficiency* / Q000235:genetics
D064231:Nestin; D017382:Reactive Oxygen Species; D051140:Selenoproteins; C547431:selenoprotein T, mouse; C045073:Cre recombinase; D019426:Integrases
Antioxidant; Behavioral deficit; Brain ontogenesis; Knockout mice; Neuroprotection