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Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation.
Exp Neurol 2004; 187(1):105-17EN

Abstract

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.

Authors+Show Affiliations

Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15081593

Citation

Heikkinen, T, et al. "Estrogen Treatment Improves Spatial Learning in APP + PS1 Mice but Does Not Affect Beta Amyloid Accumulation and Plaque Formation." Experimental Neurology, vol. 187, no. 1, 2004, pp. 105-17.
Heikkinen T, Kalesnykas G, Rissanen A, et al. Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation. Exp Neurol. 2004;187(1):105-17.
Heikkinen, T., Kalesnykas, G., Rissanen, A., Tapiola, T., Iivonen, S., Wang, J., ... Puoliväli, J. (2004). Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation. Experimental Neurology, 187(1), pp. 105-17.
Heikkinen T, et al. Estrogen Treatment Improves Spatial Learning in APP + PS1 Mice but Does Not Affect Beta Amyloid Accumulation and Plaque Formation. Exp Neurol. 2004;187(1):105-17. PubMed PMID: 15081593.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation. AU - Heikkinen,T, AU - Kalesnykas,G, AU - Rissanen,A, AU - Tapiola,T, AU - Iivonen,S, AU - Wang,J, AU - Chaudhuri,J, AU - Tanila,H, AU - Miettinen,R, AU - Puoliväli,J, PY - 2003/06/23/received PY - 2003/12/30/revised PY - 2004/01/15/accepted PY - 2004/4/15/pubmed PY - 2004/5/11/medline PY - 2004/4/15/entrez SP - 105 EP - 17 JF - Experimental neurology JO - Exp. Neurol. VL - 187 IS - 1 N2 - 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. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/15081593/Estrogen_treatment_improves_spatial_learning_in_APP_+_PS1_mice_but_does_not_affect_beta_amyloid_accumulation_and_plaque_formation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014488604000378 DB - PRIME DP - Unbound Medicine ER -