母体的胆碱补充对唐氏综合征的Ts65Dn小鼠模型的海马胆碱能系统的影响

Title:Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome

Volume: 13 Issue: 1

Author(s): Christy M. Kelley, Jessica A. Ash, Brian E. Powers, Ramon Velazquez, Melissa J. Alldred, Milos D. Ikonomovic and Stephen D. Ginsberg, Barbara J. Strupp and Elliott J. Mufson

Affiliation:

关键词: Aging

摘要: Down syndrome (DS), caused by trisomy of chromosome 21, is marked by intellectual disability (ID) and early onset of Alzheimer’s disease (AD) neuropathology including hippocampal cholinergic projection system degeneration. Here we determined the effects of age and maternal choline supplementation (MCS) on hippocampal cholinergic deficits in Ts65Dn mice compared to 2N mice sacrificed at 6-8 and 14-18 months of age. Ts65Dn mice and disomic (2N) littermates sacrificed at ages 6-8 and 14-18 mos were used for an aging study and Ts65Dn and 2N mice derived from Ts65Dn dams were maintained on either a choline-supplemented or a choline-controlled diet (conception to weaning) and examined at 14-18 mos for MCS studies. In the latter, mice were behaviorally tested on the radial arm Morris water maze (RAWM) and hippocampal tissue was examined for intensity of choline acetyltransferase (ChAT) immunoreactivity. Hippocampal ChAT activity was evaluated in a separate cohort. ChAT-positive fiber innervation was significantly higher in the hippocampus and dentate gyrus in Ts65Dn mice compared with 2N mice, independent of age or maternal diet. Similarly, hippocampal ChAT activity was significantly elevated in Ts65Dn mice compared to 2N mice, independent of maternal diet. A significant increase with age was seen in hippocampal cholinergic innervation of 2N mice, but not Ts65Dn mice. Degree of ChAT intensity correlated negatively with spatial memory ability in unsupplemented 2N and Ts65Dn mice, but positively in MCS 2N mice. The increased innervation produced by MCS appears to improve hippocampal function, making this a therapy that may be exploited for future translational approaches in human DS.

Cite this article as:

Christy M. Kelley, Jessica A. Ash, Brian E. Powers, Ramon Velazquez, Melissa J. Alldred, Milos D. Ikonomovic and Stephen D. Ginsberg, Barbara J. Strupp and Elliott J. Mufson , Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome, Current Alzheimer Research 2016; 13 (1) . https://dx.doi.org/10.2174/1567205012666150921100515