Change in Brain Plasmalogen Composition by Exposure to Prenatal Undernutrition Leads to Behavioral Impairment of Rats.

Epidemiological studies suggest that poor nutrition during pregnancy influences offspring predisposition to experience developmental and psychiatric disorders. Animal studies have shown that maternal undernutrition leads to behavioral impairment, which is linked to alterations in monoaminergic systems and inflammation in the brain. In this study, we focused on the ethanolamine plasmalogen of the brain as a possible contributor to behavioral disturbances observed in offspring exposed to maternal undernutrition. Maternal food or protein restriction between gestational day (GD) 5.5 and GD 10.5 resulted in hyperactivity of rat male adult offspring. Genes related to the phospholipid biosynthesis were found to be activated in the PFC, but not in the NAcc or striatum, in the offspring exposed to prenatal undernutrition. Corresponding to these gene activations, increased ethanolamine plasmalogen (18:0p-22:6) was observed in the PFC using mass spectrometry imaging. A high number of crossings and the long time spent in the center area were observed in the offspring exposed to prenatal undernutrition and were mimicked in adult rats via the intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome. Additionally, plasmalogen (18:0p-22:6) increased only in the PFC, and not in the NAcc or striatum. These results suggest that brain plasmalogen is one of the key molecules to control behavior, and its injection using liposome is a potential therapeutic approach for cognitive impairment.SIGNIFICANCE STATEMENT Maternal undernutrition correlates to developmental and psychiatric disorders. Here, we found that maternal undernutrition in early pregnancy led to hyperactivity in rat male offspring and induced gene activation of phospholipid-synthesizing enzyme and elevation of ethanolamine plasmalogen (18:0p-22:6) level in the PFC. Intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome maintained crossing activity and the activity was circumscribed to the center area for a long time period, as in prenatally undernourished offspring with aberrant behavior. Furthermore, the amount of ethanolamine plasmalogen (18:0p-22:6) increased in the PFC of the rat after injection. Our result suggests that brain plasmalogen is one of the key molecules to control behavior and that its injection using liposome is a potential therapeutic approach for cognitive impairment.

Maternal undernutrition during early pregnancy inhibits postnatal growth of the tibia in the female offspring of rats by alteration of chondrogenesis.

Epidemiological research has suggested that birth weights are correlated with adult leg lengths. However, the relationship between prenatal undernutrition (UN) and postnatal leg growth remains controversial. We investigated the effects of UN during early pregnancy on postnatal hindlimb growth and determined whether early embryonic malnutrition affects the functions of postnatal chondrocytes in rats. Undernourished Wistar dams were fed 40% of the daily intake of rats in the control groups from gestational days 5.5-11.5, and femurs, tibias, and trunks or spinal columns were morphologically measured at birth and at 16 weeks of age in control and undernourished offspring of both sexes. We evaluated cell proliferation and differentiation of cultured chondrocytes derived from neonatal tibias of female offspring and determined chondrocyte-related gene expression levels in neonatal epiphysis and embryonic limb buds. Tibial lengths of undernourished female, but not male, offspring were longer at birth and shorter at 16 weeks of age (p < .05) compared with those of control rats. In chondrocyte culture studies, stimulating effects of IGF-1 on cell proliferation (p < .01) were significantly decreased and levels of type II collagen were lower in female undernourished offspring (p < .05). These phenomena were accompanied by decreased expression levels of Col2a1 and Igf1r and increased expression levels of Fgfr3 (p < .05), which might be attributable to the decreased expression of specificity protein 1 (p < .05), a key transactivator of Col2a1 and Igf1r. In conclusion, UN stress during early pregnancy reduces postnatal tibial growth in female offspring by altering the function of chondrocytes, likely reflecting altered expression of gene transactivators.

Experimental demonstration of the induction synchrotron.

We report an experimental demonstration of the induction synchrotron, the concept of which has been proposed as a future accelerator for the second generation of neutrino factory or hadron collider. The induction synchrotron supports a superbunch and a superbunch permits more charge to be accelerated while observing the constraints of the transverse space-charge limit. By using a newly developed induction acceleration system instead of radio-wave acceleration devices, a single proton bunch injected from the 500 MeV booster ring and captured by the barrier bucket created by the induction step voltages was accelerated to 6 GeV in the KEK proton synchrotron.