Frontal cortex BDNF levels correlate with working memory in an animal model of Down syndrome.
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.
Bimonte-Nelson
Heather A
HA
Department of Physiology and Neuroscience and the Center for Studies on Aging, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
Hunter
Christopher L
CL
Nelson
Matthew E
ME
Granholm
Ann-Charlotte E
AC
D000818:Animals; D001522:Behavior, Animal; D001923:Brain Chemistry / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis*; D002540:Cerebral Cortex / Q000737:chemistry*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000503:physiopathology*; D004924:Escape Reaction; D005625:Frontal Lobe / Q000737:chemistry*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000503:physiopathology; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D020932:Nerve Growth Factor / Q000032:analysis
D019208:Brain-Derived Neurotrophic Factor; D020932:Nerve Growth Factor