Specific neurodevelopmental damage in mice offspring following maternal inflammation during pregnancy.
Intrauterine inflammation is a major risk for offspring neurodevelopmental brain damage and may result in cognitive limitations and poor cognitive and perceptual outcomes. Pro-inflammatory cytokines, stimulated during inflammatory response, have a pleotrophic effect on neurons and glia cells. They act in a dose-dependent manner, activate cell-death pathways and also act as trophic factors. In the present study, we have examined in mice the effect of short, systemic maternal inflammation on fetal brain development. Maternal inflammation, induced by lipopolysaccharide (LPS) at gestation day 17, did not affect morphogenic parameters and reflex development during the first month of life. However, maternal inflammation specifically increased the number of pyramidal and granular cells in the hippocampus, as well as the shrinkage of pyramidal cells, but not of the granular cells. No additional major morphological differences were observed in the cerebral cortex or cerebellum. In accordance with the morphological effects, maternal inflammation specifically impaired distinct forms of learning and memory, but not motor function or exploration in the adult offspring. The specific deficiency observed, following maternal inflammation, may suggest particular sensitivity of the hippocampus and other associated brain regions to inflammatory factors during late embryonic development.
Golan
H M
HM
Department of Developmental Molecular Genetics and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel. havag@bgumail.bgu.ac.il
Lev
V
V
Hallak
M
M
Sorokin
Y
Y
Huleihel
M
M
D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D047108:Embryonic Development; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013154:Spleen / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D008070:Lipopolysaccharides; D020932:Nerve Growth Factor