TY - JOUR
T1 - Behavioral comparison of 4 and 6 month-old Ts65Dn mice
T2 - Age-related impairments in working and reference memory
AU - Hunter, Christopher L.
AU - Bimonte, Heather A.
AU - Granholm, Ann Charlotte E.
N1 - Funding Information:
We thank Dr. Lynn Hyde for valuable scientific discussion and Alfred Moore for excellent technical assistance. This work was funded by NIH grants AG12122, AG04418, and AG10755.
PY - 2003/1/22
Y1 - 2003/1/22
N2 - Ts65Dn mice are partially trisomic for a segment of murine chromosome 16 similar to the gene segment on human chromosome 21 affected in Down's syndrome (DS). These animals display cognitive deficits, neurochemical imbalances, and cholinergic degeneration resembling alterations in DS and early onset Alzheimer's disease. The loss of basal forebrain cholinergic phenotype in Ts65Dn mice begins at approximately 6 months of age and may be due to an improperly functioning neurotrophic system. We compared 4 and 6 month-old Ts65Dn mice in a water-escape radial-arm maze task to investigate working and reference memory before and after the reported onset of cholinergic decline. Both 4 and 6 month-old Ts65Dn mice exhibited impaired performance compared to age-matched controls. However, the younger Ts65Dn mice displayed the capability to learn all working and reference memory measures, while the older Ts65Dn mice did not. Ts65Dn mice failed to maintain performance as working memory load increased, and the ability to handle an increasing working memory load also diminished with age. Collectively, these data suggest that major alterations in cognitive function occur in Ts65Dn mice between the ages of 4 and 6 months.
AB - Ts65Dn mice are partially trisomic for a segment of murine chromosome 16 similar to the gene segment on human chromosome 21 affected in Down's syndrome (DS). These animals display cognitive deficits, neurochemical imbalances, and cholinergic degeneration resembling alterations in DS and early onset Alzheimer's disease. The loss of basal forebrain cholinergic phenotype in Ts65Dn mice begins at approximately 6 months of age and may be due to an improperly functioning neurotrophic system. We compared 4 and 6 month-old Ts65Dn mice in a water-escape radial-arm maze task to investigate working and reference memory before and after the reported onset of cholinergic decline. Both 4 and 6 month-old Ts65Dn mice exhibited impaired performance compared to age-matched controls. However, the younger Ts65Dn mice displayed the capability to learn all working and reference memory measures, while the older Ts65Dn mice did not. Ts65Dn mice failed to maintain performance as working memory load increased, and the ability to handle an increasing working memory load also diminished with age. Collectively, these data suggest that major alterations in cognitive function occur in Ts65Dn mice between the ages of 4 and 6 months.
KW - Down's syndrome
KW - Radial-arm maze
KW - Reference memory
KW - Ts65Dn
KW - Working memory
KW - Working memory load
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U2 - 10.1016/S0166-4328(02)00275-9
DO - 10.1016/S0166-4328(02)00275-9
M3 - Article
C2 - 12527443
AN - SCOPUS:0037460101
SN - 0166-4328
VL - 138
SP - 121
EP - 131
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -