title: Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice.
abstract: Down syndrome (DS) is marked by intellectual disability (ID) and early-onset of Alzheimer's disease (AD) neuropathology, including basal forebrain cholinergic neuron (BFCN) degeneration. The present study tested the hypothesis that maternal choline supplementation (MCS) improves spatial mapping and protects against BFCN degeneration in the Ts65Dn mouse model of DS and AD. During pregnancy and lactation, dams were assigned to either a choline sufficient (1.1g/kg choline chloride) or choline supplemented (5.0g/kg choline chloride) diet. Between 13 and 17months of age, offspring were tested in the radial arm water maze (RAWM) to examine spatial mapping followed by unbiased quantitative morphometry of BFCNs. Spatial mapping was significantly impaired in unsupplemented Ts65Dn mice relative to normal disomic (2N) littermates. Additionally, a significantly lower number and density of medial septum (MS) hippocampal projection BFCNs was also found in unsupplemented Ts65Dn mice. Notably, MCS significantly improved spatial mapping and increased number, density, and size of MS BFCNs in Ts65Dn offspring. Moreover, the density and number of MS BFCNs correlated significantly with spatial memory proficiency, providing support for a functional relationship between these behavioral and morphometric effects of MCS for trisomic offspring. Thus, increasing maternal choline intake during pregnancy may represent a safe and effective treatment approach for expectant mothers carrying a DS fetus, as well as a possible means of BFCN neuroprotection during aging for the population at large.
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Ash
authors.affiliation: Department of Psychology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Velazquez
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Christy M
authors.initials: CM
authors.lastname: Kelley
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Powers
authors.affiliation: Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA; Departments of Psychiatry and Physiology & Neuroscience, New York University Langone Medical Center, New York, NY 10962, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Ginsberg
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; Department of Psychology, Cornell University, Ithaca, NY 14853, USA. Electronic address: bjs13@cornell.edu.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Strupp
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D066187:Basal Forebrain / Q000473:pathology*; D002452:Cell Count; D048429:Cell Size; D002794:Choline / Q000008:administration & dosage*; D059329:Cholinergic Neurons / Q000473:pathology*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D018782:Maze Learning / Q000502:physiology*; D008822:Mice, Transgenic; D011247:Pregnancy; D011897:Random Allocation; D065852:Spatial Memory / Q000502:physiology; D014314:Trisomy
chemical_list: D002794:Choline
keywords: Alzheimer's disease; Down syndrome; Hippocampus; Medial septum; Nucleus basalis; Radial arm water maze; Spatial memory; Stereology; Vertical limb of the diagonal band