Behavioral and neurobiological markers of Alzheimer's disease in Ts65Dn mice: effects of estrogen.
Individuals with Down's syndrome (DS) develop neuropathological features similar to Alzheimer's disease (AD) early in life, including dementia, accumulation of beta-amyloid, and irregular phosphorylation of tau proteins. Ts65Dn mice, an animal model of DS, provide a unique method to investigate the mechanisms related to AD-like symptoms in DS and possible therapeutic interventions. Ts65Dn mice undergo a decline in cholinergic phenotype and cognitive deterioration beginning at 6-8 months of age. In middle-aged female Ts65Dn mice, estrogen supplementation alleviated these cholinergic and cognitive impairments. The current study investigated AD-like markers and the effects of estrogen in male Ts65Dn mice. Estrogen treatment prior to behavioral testing did not improve cognitive deficits in 6-month-old male Ts65Dn mice, but decreased total and phosphorylated (pS199) tau in the entorhinal cortex compared to normosomic animals. Hippocampal beta-amyloid(1-42) levels were increased in Ts65Dn animals, regardless of estrogen treatment. These findings further support Ts65Dn mice as a model for specific AD-like symptoms, and demonstrate that estrogen treatment of this type does not improve the cognitive ability of male Ts65Dn mice.
Hunter
Christopher L
CL
Department of Physiology and Neuroscience and the Center on Aging, Medical University of South Carolina, 26 Bee Street, Charleston, SC 29425, USA.
Bimonte-Nelson
Heather A
HA
Nelson
Mathew
M
Eckman
Christopher B
CB
Granholm
Ann-Charlotte
AC
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000503:physiopathology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D018696:Neuroprotective Agents / Q000378:metabolism*; D016037:Single-Blind Method; D014314:Trisomy; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D018696:Neuroprotective Agents; D016875:tau Proteins; D004958:Estradiol