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P1‐103: COMPOUND E411 RESCUES TRACE FEAR MEMORY DEFICIT IN TRIPLE‐TRANSGENIC ALZHEIMER'S DISEASE MICE
Author(s) -
Varinthra Peeraporn,
Ganesan Kiruthika,
Huang Shun-Ping,
Liu Ingrid Y.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.658
Subject(s) - neurotoxicity , hippocampus , neuroprotection , neuroscience , genetically modified mouse , hippocampal formation , fear conditioning , transgene , medicine , psychology , pathology , biology , toxicity , biochemistry , gene , amygdala
Background: This research demonstrates that a compound E411, derived from soft coral, may treat deficit of memory retrieval of triple-transgenic Alzheimer’s disease (3xTg-AD) mice. Alzheimer’s disease (AD) is a neurodegenerative disease and inflammatory brain disorder. The main pathology of AD consists of Ab deposition and intracellular hyperphosphorylated neurofibrillary tangles of tau. The 3xTg-AD mouse is an animal model of AD that exhibits both beta-amyloid and tau pathology mimicking early pathology of human AD. Previous studies have reported that the 3xTg-AD mouse shows impaired spatial and contextual fear memory at 6 months of age. The increased levels of inflammatory cytokines such as TNF-a, COX-2 and iNOS cause memory deficit which lead to synaptic dysfunction, synaptic loss, and neurotoxicity in the brain. However, the effective approach for the prevention or treatment of AD is not yet discovered. E411 is a compound derived from the soft coral. It has been shown to have anti-inflammatory and neuroprotective effects which inhibits iNOS and COX-2 expression in the optic nerve crush model in rats and against the 6-hydroxydopamine-induced neurotoxicity in neuroblastoma SH-SY5Y. This research aims to investigate whether compound E411 can rescue fear memory deficit in 3xTg-AD mice. Methods: Wild type mice (n1⁄45/group) trained with trace fear conditioning (TFC) and treated with/without compound E411. Brain tissues were collected to measure dendritic spine density in the hippocampal region. Then, compound E411 were tested in 6-monthold 3xTg-AD mice (n1⁄48 /group) to investigate their effect in TFC. Brain tissues and proteins were collected to measure the expression of inflammatory markers including TNF-a, COX-2, and iNOS. Results: Wild type mice trained with TFC and treated with/without compound E411 demonstrated that compound E411 increased contextual memory retrieval and dendritic spine density in the hippocampal region. Moreover, compound E411 also significantly increased contextual memory retrieval and enhanced cued memory retrieval when compared to 3xTg-AD untreated group (p 0.05) by suppressing inflammatory markers including TNF-a, COX-2, and iNOS in the hippocampal CA3 region and the basolateral amygdala of 3xTg-AD mice. Conclusions: Our results suggest that compound E411 might act as anti-inflammatory drug that can help reverse memory deficit in AD mice.