Maternal dietary choline availability alters mitosis, apoptosis and the localization of TOAD-64 protein in the developing fetal rat septum

Maternal changes in dietary choline availability alter brain biochemistry a nd hippocampal development in the offspring resulting in lifelong behaviora l changes in the offspring. In order to better understand the relationship between maternal diet, brain cytoarchitecture and behavior, we investigated the effects of choline availability on cell proliferation, apoptosis and d ifferentiation in the fetal rat brain septum. Timed-pregnant rats on day E1 2 were fed AIN-76 diet with varying levels of dietary choline for 6 days. W e found that choline deficiency (CD) significantly decreased the rate of mi tosis in the progenitor neuroepithelium adjacent to the septum. In addition , we found an increased number of apoptotic cells in the septum of CD anima ls compared to controls (3.5 +/- 0.5 vs. 1.7 +/- 0.5 apoptotic cells per se ction; p < 0.05). However, CD had no effect on apoptosis in the indusium gr iseum (IG), a region of cortex dorsal to the septum. Using an unbiased imag e analysis method and a monoclonal antibody we found a decreased expression of the TOAD-64 kDa protein, a marker of commitment to neuronal differentia tion during fetal development, in the dorsal lateral septum of CD animals. CD also decreased the expression of TOAD-64 kDa protein in the IG and corti cal plate adjacent to the septum. These results show that dietary choline a vailability during pregnancy alters the timing of mitosis, apoptosis and th e early commitment to neuronal differentiation by progenitor cells in regio ns of the fetal brain septum, as well as hippocampus, two brain regions kno wn to be associated with learning and memory. (C) 1999 Elsevier Science B.V . All rights reserved.