Choline availability alters embryonic development of the hippocampus and septum in the rat

Choline availability in the diet during pregnancy alters fetal brain bioche mistry with resulting behavioral changes that persist throughout the lifeti me of the offspring. Tn the present study, the effects of dietary choline o n cell proliferation, migration, and apoptosis in neuronal progenitor cells in the hippocampus and septum were analyzed in fetal brains at different s tages of embryonic development. Timed-pregnant rats on day E12 were fed AIN -76 diet with varying levels of dietary choline for 6 days, and, on days E1 8 or E20, fetal brain sections were collected. We found that choline defici ency (CD) significantly decreased the rate of mitosis in the neuroepitheliu m adjacent to the hippocampus. An increased number of apoptotic cells were found in the region of the dentate gyrus of CD hippocampus compared to cont rols (5.5 +/- 0.7 vs. 1.9 +/- 0.3 apoptotic cells per section; p < 0.01). U sing a combination of bromodeoxyuridine (BrdU) labeling and an unbiased com puter-assisted image analysis method, we found that modulation of dietary c holine availability changed the distribution and migration of precursor cel ls born on E16 in the fimbria, primordial dentate gyrus, and Ammon's horn o f the fetal hippocampus. CD also decreased the migration of newly born cell s from the neuroepithelium into the lateral septum, thus indicating that th e sensitivity of fetal brain to choline availability is not restricted to t he hippocampus. We found an increase in the expression of TOAD-64 protein, an early neuronal differentiation marker, in the hippocampus of CD day E18 fetal brains compared to controls. These results show that dietary choline availability alters the timing of the genesis, migration, and commitment to differentiation of progenitor neuronal-type cells in fetal brain hippocamp al regions known to be associated with learning and memory processes in adu lt brain. (C) 1999 Elsevier Science B.V. All rights reserved.