| Choline supplementation during fetal development (embryonic days (E) 11-17) permanently enhances memory performance, while prenatal choline deficiency has been shown to accelerate age-related declines in timing in rats. To characterize the neurochemical mechanisms that may mediate these behavioral effects, we investigated the development of indices of the cholinergic system in the hippocampus: choline acetyltransferase (ChAT), acetylcholinesterase (AChE), synthesis of acetylcholine (ACh) from choline transported by the high-affinity choline-uptake (HACU), and potassium-evoked ACh release. During E11-17 Sprague-Dawley pregnant rats consumed 0 (choline-deficient), 1.3 (control), and 4.6 (choline-supplemented) mmol/kg/day of choline, respectively. On postnatal days (P) 17 and 27 male hippocampi of the deficient animals had elevated AChE and ChAT activities, and increased synthesis of ACh from choline transported by HACU, concomitant with reductions of tissue ACh content relative to the control and supplemented rats, and an inability to sustain depolarization-evoked ACh release relative to the supplemented animals. In contrast, AChE and ChAT activities, and ACh synthesized from choline transported by HACU were lowest in supplemented rats while depolarization-evoked ACh release was the highest. This pattern of changes suggests that the hippocampi of the deficient animals are characterized by fast ACh recycling and efficient choline reutilization for ACh synthesis. In the supplemented animals, ACh turnover and choline recycling were slower than in the control and deficinet groups, while the evoked release of ACh was higher. In similar studies in aged rats (26.5 months), ACh content of hippocampal slices following depolarization-evoked ACh release was highest in prenatally choline-supplemented rats. Together, the data show a complex adaptive response of the hippocampal cholinergic system to prenatal choline availability and provide a novel example of developmental plasticity in the nervous system governed by the supply of a single nutrient. |
