Apoptotic neurodegeneration induced by ethanol in neonatal mice is associated with profound learning/memory deficits in juveniles followed by progressive functional recovery in adults.
Administration of ethanol to rodents during the synaptogenesis period induces extensive apoptotic neurodegeneration in the developing brain. This neurotoxicity may explain the reduced brain mass and neurobehavioral disturbances in human Fetal Alcohol Syndrome (FAS). Here, we report binge-like exposure of infant mice to ethanol on a single postnatal day triggered apoptotic death of neurons from diencephalic structures that comprise an extended hippocampal circuit important for spatial learning and memory. The ethanol exposure paradigm yielding these neuronal losses caused profound impairments in spatial learning and memory at 1 month of age. This impairment was significantly attenuated during subsequent development, indicating recovery of function. Recovery was not associated with increased neurogenesis, suggesting plastic reorganization of neuronal networks compensated for early neuronal losses. We hypothesize that neuroapoptotic damage in homologous regions of human brain underlies cognitive deficits in FAS and the human brain of FAS victims has a similar capacity to effect functional recovery.
Wozniak
David F
DF
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
Hartman
Richard E
RE
Boyle
Maureen P
MP
Vogt
Sherri K
SK
Brooks
Ashley R
AR
Tenkova
Tatyana
T
Young
Chainllie
C
Olney
John W
JW
Muglia
Louis J
LJ
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001973:Bromodeoxyuridine; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology*; D011187:Posture; D011247:Pregnancy; D012727:Sex Characteristics
D000431:Ethanol; D001973:Bromodeoxyuridine