Perinatal Choline Supplementation Improves Cognitive Functioning and Emotion Regulation in the Ts65Dn Mouse Model of Down Syndrome

Overview

Journal Behav Neurosci

Publisher American Psychological Association

Specialty Psychology

Date 2010 Jun 10

PMID 20528079

Citations 74

Authors

Jisook Moon

May Chen

Shruti U Gandhy

Myla Strawderman

David A Levitsky

Kenneth N Maclean

Barbara J Strupp

Affiliations

Soon will be listed here.

Abstract

In addition to mental retardation, individuals with Down syndrome (DS) also develop the neuropathological changes typical of Alzheimer's disease (AD) and the majority of these individuals exhibit dementia. The Ts65Dn mouse model of DS exhibits key features of these disorders, including early degeneration of cholinergic basal forebrain (CBF) neurons and impairments in functions dependent on the two CBF projection systems; namely, attention and explicit memory. Herein, we demonstrate that supplementing the maternal diet with excess choline during pregnancy and lactation dramatically improved attentional function of the adult trisomic offspring. Specifically, the adult offspring of choline-supplemented Ts65Dn dams performed significantly better than unsupplemented Ts65Dn mice on a series of 5 visual attention tasks, and in fact, on some tasks did not differ from the normosomic (2N) controls. A second area of dysfunction in the trisomic animals, heightened reactivity to committing an error, was partially normalized by the early choline supplementation. The 2N littermates also benefited from increased maternal choline intake on 1 attention task. These findings collectively suggest that perinatal choline supplementation might significantly lessen cognitive dysfunction in DS and reduce cognitive decline in related neurodegenerative disorders such as AD.

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References

Driscoll L, Carroll J, Moon J, Crnic L, Levitsky D, Strupp B . Impaired sustained attention and error-induced stereotypy in the aged Ts65Dn mouse: a mouse model of Down syndrome and Alzheimer's disease. Behav Neurosci. 2004; 118(6):1196-205. DOI: 10.1037/0735-7044.118.6.1196. View

Bowes C, Li T, Frankel W, Danciger M, Coffin J, Applebury M . Localization of a retroviral element within the rd gene coding for the beta subunit of cGMP phosphodiesterase. Proc Natl Acad Sci U S A. 1993; 90(7):2955-9. PMC: 46215. DOI: 10.1073/pnas.90.7.2955. View

Capone G . Down syndrome: advances in molecular biology and the neurosciences. J Dev Behav Pediatr. 2001; 22(1):40-59. DOI: 10.1097/00004703-200102000-00007. View

Wisniewski K, Dalton A, McLachlan C, Wen G, Wisniewski H . Alzheimer's disease in Down's syndrome: clinicopathologic studies. Neurology. 1985; 35(7):957-61. DOI: 10.1212/wnl.35.7.957. View

Ricceri L, Berger-Sweeney J . Postnatal choline supplementation in preweanling mice: sexually dimorphic behavioral and neurochemical effects. Behav Neurosci. 1999; 112(6):1387-92. View

Cheng R, MacDonald C, Williams C, Meck W . Prenatal choline supplementation alters the timing, emotion, and memory performance (TEMP) of adult male and female rats as indexed by differential reinforcement of low-rate schedule behavior. Learn Mem. 2008; 15(3):153-62. PMC: 2275657. DOI: 10.1101/lm.729408. View

Meck W, Smith R, Williams C . Pre- and postnatal choline supplementation produces long-term facilitation of spatial memory. Dev Psychobiol. 1988; 21(4):339-53. DOI: 10.1002/dev.420210405. View

Salehi A, Delcroix J, Belichenko P, Zhan K, Wu C, Valletta J . Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron. 2006; 51(1):29-42. DOI: 10.1016/j.neuron.2006.05.022. View

Tees R . The influences of rearing environment and neonatal choline dietary supplementation on spatial learning and memory in adult rats. Behav Brain Res. 1999; 105(2):173-88. DOI: 10.1016/s0166-4328(99)00074-1. View

10.

Yang Y, Liu Z, Cermak J, Tandon P, Sarkisian M, Stafstrom C . Protective effects of prenatal choline supplementation on seizure-induced memory impairment. J Neurosci. 2000; 20(22):RC109. PMC: 6773159. View

11.

Davisson M, Schmidt C, Akeson E . Segmental trisomy of murine chromosome 16: a new model system for studying Down syndrome. Prog Clin Biol Res. 1990; 360:263-80. View

12.

Reeves R, Irving N, Moran T, WOHN A, Kitt C, Sisodia S . A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet. 1995; 11(2):177-84. DOI: 10.1038/ng1095-177. View

13.

Granholm A, Ford K, Hyde L, Bimonte H, Hunter C, Nelson M . Estrogen restores cognition and cholinergic phenotype in an animal model of Down syndrome. Physiol Behav. 2002; 77(2-3):371-85. DOI: 10.1016/s0031-9384(02)00884-3. View

14.

Tees R, Mohammadi E . The effects of neonatal choline dietary supplementation on adult spatial and configural learning and memory in rats. Dev Psychobiol. 1999; 35(3):226-40. View

15.

Escorihuela R, Fernandez-Teruel A, Vallina I, Baamonde C, Lumbreras M, Dierssen M . A behavioral assessment of Ts65Dn mice: a putative Down syndrome model. Neurosci Lett. 1995; 199(2):143-6. DOI: 10.1016/0304-3940(95)12052-6. View

16.

Li Q, Guo-Ross S, Lewis D, Turner D, White A, Wilson W . Dietary prenatal choline supplementation alters postnatal hippocampal structure and function. J Neurophysiol. 2003; 91(4):1545-55. DOI: 10.1152/jn.00785.2003. View

17.

Kaisho Y, Ohta H, Miyamoto M, Igarashi K . Nerve growth factor promoter driven neurotrophin-3 overexpression in the mouse and the protective effect of transgene on age-related behavioral deficits. Neurosci Lett. 2000; 277(3):181-4. DOI: 10.1016/s0304-3940(99)00874-5. View

18.

Wisniewski K, Wisniewski H, Wen G . Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol. 1985; 17(3):278-82. DOI: 10.1002/ana.410170310. View

19.

Robbins T . The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology (Berl). 2002; 163(3-4):362-80. DOI: 10.1007/s00213-002-1154-7. View

20.

Cataldo A, Petanceska S, Peterhoff C, Terio N, Epstein C, Villar A . App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of down syndrome. J Neurosci. 2003; 23(17):6788-92. PMC: 6740714. View