Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation.
We investigated the effects of ovariectomy (OVX) and 17 beta-estradiol (0.18 mg per pellet) treatment on spatial learning and memory, hippocampal beta amyloid (A beta) levels, and amyloid plaque counts in double transgenic mice (A/P) carrying mutated amyloid precursor protein (APPswe) and presenilin-1 (PS1-A246E). After OVX at 3 months of age, the mice received estrogen treatment for the last 3 months of their lifetime before they were killed at 6, 9, or 12 months of age. Estrogen treatment in A/P OVX mice increased the number of correct choices in a position discrimination task in the T-maze, and slightly improved their performance in a win-stay task (1/8 arms baited) in the radial arm maze (RAM). However, estrogen treatment did not reverse the A beta-dependent cognitive deficits of A/P mice in the water maze (WM) spatial navigation task. Furthermore, ovariectomy or estrogen treatment in OVX and sham-operated A/P mice had no effect on hippocampal amyloid accumulation. These results show that the estrogen treatment in a transgenic mouse model of Alzheimer's disease (AD) improves performance in the same learning and memory tasks as in the normal C57BL/6J mice. However, the estrogen effects in these mice appeared to be unrelated to A beta-induced cognitive deficits. Our results do not support the idea that estrogen treatment decreases the risk or alleviates the symptoms of Alzheimer's disease by inhibiting the accumulation of A beta or formation of amyloid plaques.
Heikkinen
T
T
Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland.
Kalesnykas
G
G
Rissanen
A
A
Tapiola
T
T
Iivonen
S
S
Wang
J
J
Chaudhuri
J
J
Tanila
H
H
Miettinen
R
R
Puoliväli
J
J
D000367:Age Factors; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D018782:Maze Learning / Q000187:drug effects*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D053764:Presenilin-1; D013037:Spatial Behavior / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004967:Estrogens; D008565:Membrane Proteins; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D004958:Estradiol