Grant: Regional Partnership Program Fellowship

The creatine system (creatine, creatine-phosphate and creatine kinase) plays three critical roles: ATP buffering, vectorial energy translocation and regulation of mitochondrial ROS production. Although creatine has long been known to play a major role in muscle metabolism, only recently it has become apparent that it also plays a crucial role in brain function, especially during development. Infants with defective creatine synthesis develop epilepsy, speech delay and mental retardation. The accretion of creatine by neonatal animals is therefore a critical issue. All animals lose creatine via spontaneous conversion to creatinine, at a rate of 1.7% per day. In addition, lactating animals face the challenge of providing creatine to their progeny via the maternal milk. We propose to examine creatine synthesis in lactating females using the lactating rat model. The principal hypothesis is that lactation places an important demand on creatine and creatine synthesis must be up-regulated accordingly. The overall objective is to determine the origin of creatine in milk and understand the regulation of its synthesis in lactating females. Four specific objectives 1. To measure the extent to which lactation increases the demand on creatine synthesis in lactating females. 2. To elucidate the origin of creatine in maternal milk 3. To characterize the relation between the events related to lactation and creatine synthesis. 4. To ascertain whether prolactin (the lactation hormone) has an effect on creatine synthesis.