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P2‐399: Transplantation of epigenetically altered human bone marrow‐derived stem cells in an Alzheimer transgenic mouse model
Author(s) -
Marutle Amelia,
Hossain Monowar,
Sugaya Kiminobu
Publication year - 2008
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.2008.05.1477
Subject(s) - dentate gyrus , genetically modified mouse , biology , hippocampal formation , transplantation , transgene , stem cell , neural stem cell , hippocampus , microbiology and biotechnology , pathology , neuroscience , medicine , biochemistry , gene
investigated the endocannabinoid receptor stimulation effect on inflammation in aged animals using 24 months old rats with chronic treatment of 0.5 or 2 mg/kg/day with or without an antagonist of CB1 and/or an antagonist of CB2. Results: Our results indicate that WIN-2 (2mg/kg/d): 1) reversed LPS-induced microglia activation in the hippocampus and restored spatial memory deficits in the water maze task. Further, WIN-2 increased neurogenesis in the dentate gyrus. Our results further indicate that the antiinflammatory effect observed in aged rats may be linked to the antagonistic properties of the WIN-2 compound at TRPV1 receptors while the increase in hippocampal neurogenesis was due to stimulation of CB1 and CB2 receptors. Conclusions: We are currently exploring the potential additive benefits of using WIN-2 (0.5mg/kg or 2mg/kg) combined with memantine (5mg/kg/d or 20mg/kg/d) on the effects of aging on neuroinflammation and neurogenesis in order to determine the possibility of using endocannabinoids in combination with a currently available treatment for the treatment of the dementia symptoms associated with Alzheimer’s disease. These results provide evidence that selective manipulation of the endocannabinoid system may effectively prevent or slow the progress of illness in diseases involving neuroinflammation.