In vivo MRI identifies cholinergic circuitry deficits in a Down syndrome model

Yuanxin Chen, Victor V. Dyakin, Craig A. Branch, Babak Ardekani, Dunsheng Yang, David N. Guilfoyle, Jesse Peterson, Corrinne Peterhoff, Stephen D. Ginsberg, Anne M. Cataldo, Ralph A. Nixon

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

In vivo quantitative magnetic resonance imaging (MRI) was employed to detect brain pathology and map its distribution within control, disomic mice (2N) and in Ts65Dn and Ts1Cje trisomy mice with features of human Down syndrome (DS). In Ts65Dn, but not Ts1Cje mice, transverse proton spin-spin (T2) relaxation time was selectively reduced in the medial septal nucleus (MSN) and in brain regions that receive cholinergic innervation from the MSN, including the hippocampus, cingulate cortex, and retrosplenial cortex. Basal forebrain cholinergic neurons (BFCNs) in the MSN, identified by choline acetyltransferase (ChAT) and nerve growth factor receptors p75NTR and TrkA immunolabeling were reduced in Ts65Dn brains and in situ acetylcholinesterase (AChE) activity was depleted distally along projecting cholinergic fibers, and selectively on pre- and postsynaptic profiles in these target areas. T2 effects were negligible in Ts1Cje mice that are diploid for App and lack BFCN neuropathology, consistent with the suspected relationship of this pathology to increased App dosage. These results establish the utility of quantitative MRI in vivo for identifying Alzheimer's disease-relevant cholinergic changes in animal models of DS and characterizing the selective vulnerability of cholinergic neuron subpopulations.

Original languageEnglish (US)
Pages (from-to)1453-1465
Number of pages13
JournalNeurobiology of Aging
Volume30
Issue number9
DOIs
StatePublished - Sep 1 2009

Keywords

  • Acetylcholine
  • Alzheimer's disease
  • Basal forebrain
  • Functional imaging
  • Medial septal nucleus
  • Ts1Cje trisomic mice
  • Ts65Dn trisomic mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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    Chen, Y., Dyakin, V. V., Branch, C. A., Ardekani, B., Yang, D., Guilfoyle, D. N., Peterson, J., Peterhoff, C., Ginsberg, S. D., Cataldo, A. M., & Nixon, R. A. (2009). In vivo MRI identifies cholinergic circuitry deficits in a Down syndrome model. Neurobiology of Aging, 30(9), 1453-1465. https://doi.org/10.1016/j.neurobiolaging.2007.11.026