Age-dependent pathways of brain energy metabolism: the suckling rat, a natural model of the ketogenic diet

As a consequence of the high fat content of maternal milk, the suckling rat may be viewed as a 'natural model' of the ketogenic diet, Changes in energ y metabolism during this period of development may give us some clues into the antiepileptic properties of the ketogenic diet. We have, therefore stud ied the postnatal evolution of local cerebral metabolic rates for glucose ( LCMRglcs) and of regional rates of cerebral uptake of beta-hydroxybutyrate (beta HB) in the developing rat between postnatal day (PN) 10 and 35. LCMRg lcs were low and homogeneous at PN10. They increased significantly in four auditory regions between PN10 and PN14, at the time of maturation of audito ry function. Between PN14 and PN17, they increased further in two auditory regions, one visual area (the lateral geniculate nucleus), three limbic and three motor areas. These increases occurred simultaneously with the matura tion of vision and the development of locomotion and general exploratory be havior. Between PN17 and PN21, LCMRglcs increased by 28-97% (depending on b rain area) and by a mean value of 25% in all areas studied. In contrast to the function-related increases in LCMRglcs, regional rates of cerebral beta HB uptake underwent a generalized non-specific increase between PN10 and P N14, and stayed at a high level until PN17. Between PN17 and PN21, rates of cerebral beta HB uptake decreased significantly in all brain regions studi ed, and reached very low levels by PN35. Thus, even in the suckling rat, wh ose cerebral metabolic activity depends upon both glucose and ketone bodies , it is the postnatal increases in LCMRglcs that appear to be critical for the acquisition of new functions and neurological competence. Conversely, t he homogeneous increase in cerebral beta HB uptake occurring between PN10 a nd PN17 at a period of active brain growth may rather reflect non-specific mechanisms of cell growth. (C) 1999 Elsevier Science B.V. All rights reserv ed.