TY - JOUR
T1 - Frontal cortex BDNF levels correlate with working memory in an animal model of Down syndrome
AU - Bimonte-Nelson, Heather A.
AU - Hunter, Christopher L.
AU - Nelson, Matthew E.
AU - Granholm, Ann Charlotte E.
N1 - Funding Information:
We thank Alfred Moore for excellent technical assistance. This work was funded by NIH grants AG12122, AG04418, and AG10755.
PY - 2003/2/17
Y1 - 2003/2/17
N2 - Individuals with Down syndrome (DS) develop most neuropathological hallmarks of Alzheimer's disease early in life, including loss of cholinergic markers in the basal forebrain. Ts65Dn mice, an animal model of DS, perform poorly on tasks requiring spatial memory and also exhibit basal forebrain pathology beginning around 6 months of age. We evaluated memory as well as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) protein levels in basal forebrain, frontal cortex, hippocampus, and striatum in Ts65Dn mice at the age when cholinergic degeneration is first observed, and compared values to normosomic controls. Six-month-old Ts65Dn mice exhibited impairments in working and reference memory as assessed on a water radial-arm maze. The working memory deficit was related to the inability of Ts65Dn mice to successfully sustain performance as the working memory load increased. Coupled with cognitive performance deficiencies, Ts65Dn mice also exhibited lower frontal cortex BDNF protein levels than controls. Further, BDNF levels were negatively correlated with working memory errors during the latter portion of testing in Ts65Dn mice, thereby suggesting that lower BDNF protein levels in the frontal cortex may be associated with the observed working memory impairment.
AB - Individuals with Down syndrome (DS) develop most neuropathological hallmarks of Alzheimer's disease early in life, including loss of cholinergic markers in the basal forebrain. Ts65Dn mice, an animal model of DS, perform poorly on tasks requiring spatial memory and also exhibit basal forebrain pathology beginning around 6 months of age. We evaluated memory as well as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) protein levels in basal forebrain, frontal cortex, hippocampus, and striatum in Ts65Dn mice at the age when cholinergic degeneration is first observed, and compared values to normosomic controls. Six-month-old Ts65Dn mice exhibited impairments in working and reference memory as assessed on a water radial-arm maze. The working memory deficit was related to the inability of Ts65Dn mice to successfully sustain performance as the working memory load increased. Coupled with cognitive performance deficiencies, Ts65Dn mice also exhibited lower frontal cortex BDNF protein levels than controls. Further, BDNF levels were negatively correlated with working memory errors during the latter portion of testing in Ts65Dn mice, thereby suggesting that lower BDNF protein levels in the frontal cortex may be associated with the observed working memory impairment.
KW - Brain-derived neurotrophic factor
KW - Down syndrome
KW - NGF
KW - Radial-arm maze
KW - Reference memory
KW - Ts65Dn
KW - Working memory
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U2 - 10.1016/S0166-4328(02)00082-7
DO - 10.1016/S0166-4328(02)00082-7
M3 - Article
C2 - 12642175
AN - SCOPUS:0037450168
SN - 0166-4328
VL - 139
SP - 47
EP - 57
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1-2
ER -