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Investigating the potential of stem cell based therapy in an immunotoxin mouse model of Alzheimer’s disease

Tiwari D, Haynes J, Short J, Pouton C (2014) Investigating the potential of stem cell based therapy in an immunotoxin mouse model of Alzheimer’s disease. Neuroscience 2014 Abstracts 295.14. Society for Neuroscience, Washington, DC.

Summary: Purpose: To characterize a dual reporter embryonic stem (ES) cell line and validate an immunotoxin mouse model of Alzheimer’s disease for future transplantation experiments. Methods: A dual (mcherry and Lhx8+) reporter ES cell line was derived from E14Tg2a mouse ES cells assessed for differentiation capability and characterized using immunocytochemistry. For the immunotoxin model, 6-8 weeks C57BL/6 male mice (n = 12) were treated with bilateral intracerebroventricular injections of saline or mu-p75-saporin toxin (0.4µg/µl/mouse) to cause cholinergic neuronal lesions. Mice were cognitively assessed using a novel water maze (WM) protocol and novel object recognition (NOR) paradigm. Immunohistochemistry was performed to detect toxin dependent neuronal loss. Results: A significant difference in learning the WM task was observed during cued and spatial trials, with toxin-treated mice showing longer latency to platform than controls (two way ANOVA; p<0.01). Also performance during probe trial was significantly reduced in treated mice (t-test; p<0.05), indicating memory loss by toxin. No memory impairment was detected using the NOR test. Immunohistochemistry for choline acetyltransferase (ChAT) confirmed a significant loss (p<0.001; t test) of cholinergic neurons in the medial septum. These data indicate that the model is appropriate for future transplantation studies. FACS analysis of reporter cell line showed a small population of Lhx8+ cells at day 6 and 10 of differentiation. Immunocytochemistry for ChAT on day 18 cells revealed few cholinergic positives neurons as compared to wild type controls. Conclusion: Literature suggests a possible role of Lhx8 in cholinergic development and these cells are being further investigated by transplantation.

Related Products: mu p75-SAP (Cat. #IT-16)