Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice

Jessica A. Ash, Ramon Velazquez, Christy M. Kelley, Brian E. Powers, Stephen D. Ginsberg, Elliott J. Mufson, Barbara J. Strupp

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 (1.1. g/kg choline chloride) or choline supplemented (5.0. g/kg choline chloride) diet. Between 13 and 17. months 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.

Original languageEnglish (US)
Pages (from-to)32-42
Number of pages11
JournalNeurobiology of Disease
Volume70
DOIs
StatePublished - Oct 2014
Externally publishedYes

Fingerprint

Cholinergic Neurons
Choline
Mothers
Down Syndrome
Nerve Degeneration
Alzheimer Disease
Pregnancy
Basal Forebrain
Lactation
Intellectual Disability
Fetus
Diet
Water

Keywords

  • Alzheimer's disease
  • Down syndrome
  • Hippocampus
  • Medial septum
  • Nucleus basalis
  • Radial arm water maze
  • Spatial memory
  • Stereology
  • Vertical limb of the diagonal band

ASJC Scopus subject areas

  • Neurology

Cite this

Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice. / Ash, Jessica A.; Velazquez, Ramon; Kelley, Christy M.; Powers, Brian E.; Ginsberg, Stephen D.; Mufson, Elliott J.; Strupp, Barbara J.

In: Neurobiology of Disease, Vol. 70, 10.2014, p. 32-42.

Research output: Contribution to journalArticle

Ash, Jessica A. ; Velazquez, Ramon ; Kelley, Christy M. ; Powers, Brian E. ; Ginsberg, Stephen D. ; Mufson, Elliott J. ; Strupp, Barbara J. / Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice. In: Neurobiology of Disease. 2014 ; Vol. 70. pp. 32-42.
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