Maternal deprivation increases cell death in the infant rat brain.
Prolonged separation from the mother can interfere with normal growth and development and is a significant risk factor for adult psychopathology. In rodents, separation of a pup from its mother increases the behavioral and endocrine responses to stress for the lifetime of the animal. Here we investigated whether maternal deprivation could affect brain development of infant rats via changes in the rate of cell death as measured by labeling the 3' end of DNA fragments using terminal transferase (ApopTag). At postnatal day 12 (P12), the number of cells undergoing cell death approximately doubled in the cerebral cortex, cerebellar cortex and in several white matter tracts following 24 h of maternal deprivation. Deprivation strongly increased the number of ApopTag-labeled cells at P6 but not at P20. Stroking the infant rats only partially reversed the effects of maternal deprivation. Increased cell death in white matter tracts correlated with an induction of nerve growth factor which has been previously associated with oligodendrocyte cell death. Cell birth was either unchanged or decreased in response to deprivation. These results indicate that maternal deprivation can alter normal brain development by increasing cell death of neurons and glia, and provides a potential mechanism by which early environmental stressors may influence subsequent behavior.
Zhang
Li Xin
LX
Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Levine
Seymour
S
Dent
Gersham
G
Zhan
Yutian
Y
Xing
Guoqiang
G
Okimoto
Darren
D
Kathleen Gordon
M
M
Post
Robert M
RM
Smith
Mark A
MA
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D016923:Cell Death / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D005260:Female; D017781:Genes, Immediate-Early / Q000502:physiology; D008297:Male; D008426:Maternal Deprivation; D020932:Nerve Growth Factor / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D020932:Nerve Growth Factor; D003345:Corticosterone