Early life stress-induced alterations in rat brain structures measured with high resolution MRI

• Published in: PloS one Vol. 12; no. 9; p. e0185061
• Main Authors: Sarabdjitsingh, R Angela, Loi, Manila, Joëls, Marian, Dijkhuizen, Rick M, van der Toorn, Annette
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.09.2017; Public Library of Science (PLoS)
• Subjects: Abnormalities; Adolescents; Animal cognition; Animals; Animals, Newborn; Anxiety; Biology and Life Sciences; Brain; Brain - diagnostic imaging; Brain - pathology; Cerebrum; Child development; Cognitive ability; Complications and side effects; Corticosterone; Deprivation; Diagnosis; Excitability; Female; Females; Glucocorticoid receptors; Illnesses; Magnetic resonance; Magnetic Resonance Imaging; Male; Males; Maternal Deprivation; Medicine and Health Sciences; Mental disorders; Mifepristone; Neostriatum; Neural networks; Neuroimaging; Neuronal Plasticity; Neurosciences; NMR; Nuclear magnetic resonance; Prefrontal cortex; Psychiatry; Psychopathology; Rats; Rats, Wistar; Receptors; Research and Analysis Methods; Risk factors; Rodents; Sex crimes; Spectrum analysis; Stress; Stress (Psychology); Stress, Psychological - diagnostic imaging; Stress, Psychological - pathology; Stresses; Structural integrity; Substantia grisea; Synaptic plasticity; White Matter - diagnostic imaging; White Matter - pathology; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0185061

Adverse experiences early in life impair cognitive function both in rodents and humans. In humans this increases the vulnerability to develop mental illnesses while in the rodent brain early life stress (ELS) abnormalities are associated with changes in synaptic plasticity, excitability and microstructure. Detailed information on the effects of ELS on rodent brain structural integrity at large and connectivity within the brain is currently lacking; this information is highly relevant for understanding the mechanism by which early life stress predisposes to mental illnesses. Here, we exposed rats to 24 hours of maternal deprivation (MD) at postnatal day 3, a paradigm known to increase corticosterone levels and thereby activate glucocorticoid receptors in the brain. Using structural magnetic resonance imaging we examined: i) volumetric changes and white/grey matter properties of the whole cerebrum and of specific brain areas; and ii) whether potential alterations could be normalized by blocking glucocorticoid receptors with mifepristone during the critical developmental window of early adolescence, i.e. between postnatal days 26 and 28. The results show that MD caused a volumetric reduction of the prefrontal cortex, particularly the ventromedial part, and the orbitofrontal cortex. Within the whole cerebrum, white (relative to grey) matter volume was decreased and region-specifically in prefrontal cortex and dorsomedial striatum following MD. A trend was found for the hippocampus. Grey matter fractions were not affected. Treatment with mifepristone did not normalize these changes. This study indicates that early life stress in rodents has long lasting consequences for the volume and structural integrity of the brain. However, changes were relatively modest and-unlike behavior- not mitigated by blockade of glucocorticoid receptors during a critical developmental period.