Brain metabolic alterations in mice subjected to postnatal traumatic stress and in their offspring.
Adverse environmental and social conditions early in life have a strong impact on health. They are major risk factors for mental diseases in adulthood and, in some cases, their effects can be transmitted across generations. The consequences of detrimental stress conditions on brain metabolism across generations are not well known. Using high-field (14.1 T) magnetic resonance spectroscopy, we investigated the neurochemical profile of adult male mice exposed to traumatic stress in early postnatal life and of their offspring, and of undisturbed control mice. We found that, relative to controls, early life stress-exposed mice have metabolic alterations consistent with neuronal dysfunction, including reduced concentration of N-acetylaspartate, glutamate and γ-aminobutyrate, in the prefrontal cortex in basal conditions. Their offspring have normal neurochemical profiles in basal conditions. Remarkably, when challenged by an acute cold swim stress, the offspring has attenuated metabolic responses in the prefrontal cortex, hippocampus and striatum. In particular, the expected stress-induced reduction in the concentration of N-acetylaspartate, a putative marker of neuronal health, was prevented in the cortex and hippocampus. These findings suggest that paternal trauma can confer beneficial brain metabolism adaptations to acute stress in the offspring.
1 Laboratory of Neuroepigenetics, University of Zurich and Swiss Federal Institute of Technology, Zürich, Switzerland.
Katharina
K
Gapp
2 Laboratory for Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Alberto
A
Corcoba
1 Laboratory of Neuroepigenetics, University of Zurich and Swiss Federal Institute of Technology, Zürich, Switzerland.
Gretchen
G
van Steenwyk
1 Laboratory of Neuroepigenetics, University of Zurich and Swiss Federal Institute of Technology, Zürich, Switzerland.
Isabelle M
IM
Mansuy
2 Laboratory for Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
João Mn
JM
Duarte
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000737:chemistry / Q000254:growth & development; D003342:Corpus Striatum / Q000737:chemistry / Q000254:growth & development; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000254:growth & development; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008426:Maternal Deprivation; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000523:psychology; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000209:etiology / Q000378:metabolism*; D013550:Swimming
Traumatic stress; magnetic resonance spectroscopy; metabolism; neurochemical profile; neurodevelopmental; transgenerational