title: Memory enhancement by Tamoxifen on amyloidosis mouse model.
abstract: Tamoxifen (TMX) is a selective estrogen receptor modulator (SERM) used in the treatment of breast cancer. Earlier studies show its neuroprotection via regulating apoptosis, microglial functions, and synaptic plasticity. TMX also showed memory enhancement in ovariectomized mice, and protection from amyloid induced damage in hippocampal cell line. These reports encouraged us to explore the role of TMX in relevance to Alzheimer's disease (AD). We report here, the effect of TMX treatment a) on memory, and b) levels of neurotransmitters (acetylcholine (ACh) and dopamine (DA)) in breeding-retired-female mice injected with beta amyloid1-42 (Aβ1-42). Mice were treated with TMX (10mg/kg, i.p.) for 15 days. In Morris water maze test, the TMX treated mice escape latency decreased during training trials. They also spent longer time in the platform quadrant on probe trial, compared to controls. In Passive avoidance test, TMX treated mice avoided stepping on the shock chamber. This suggests that TMX protects memory from Aβ induced toxicity. In frontal cortex, ACh was moderately increased, with TMX treatment. In striatum, dopamine was significantly increased, 3,4-dihydroxyphenylacetic acid (DOPAC) level and DOPAC/DA ratio was decreased post TMX treatment. Therefore, TMX enhances spatial and contextual memory by reducing dopamine metabolism and increasing ACh level in Aβ1-42 injected-breeding-retired-female mice.
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra 835215, Ranchi, India.
authors.forename: Deepika
authors.initials: D
authors.lastname: Pandey
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra 835215, Ranchi, India.
authors.forename: Sugato
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: St. Xavier's College 30, Mother Teresa Sarani, Kolkata 700016, India.
authors.forename: Mahua
authors.initials: M
authors.lastname: Basu
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra 835215, Ranchi, India. Electronic address: nmishra@bitmesra.ac.in.
authors.forename: Nibha
authors.initials: N
authors.lastname: Mishra
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000494:pharmacology; D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D016229:Amyloid beta-Peptides; D000686:Amyloidosis / Q000139:chemically induced / Q000473:pathology* / Q000523:psychology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008568:Memory / Q000187:drug effects*; D051379:Mice; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine
keywords: Aβ(1–42); Dopamine; Memory; Morris water maze; Passive avoidance; Tamoxifen;