Neuroprotective cell therapy in a sporadic Alzheimer rat model

ZAPPA VILLAR, MF; LOPEZ HANOTTE J; TRÍPODI LS; REGGIANI, PC; MOREL GR; GARCÍA, MG

Montreal

Congreso; 11th Annual Canadian Neuroscience Meeting; 2017

Canadian Association for Neuroscience

Alzheimer?s disease (AD) is the most common form of dementia. Our objective is to develop therapeutic strategies that allow preventing and/or overcoming the degenerative changes in AD. In this context, cell therapy emerges as a promising therapeutic approach. We explored the therapeutic effect (after 24 days) of human mesenchymal stem cells (hMSC) in an AD rat model by intracerebroventricular (icv) injection of streptozotocin (STZ). Intact, STZ and STZ+MSC groups were used. STZ and STZ+MSC groups received 3 mg/kg STZ-icv and, 24 hours later, the STZ+MSC group received 2x105 MSC-icv. STZ+MSC group showed a significant improvement in learning and spatial memory by the Barnes Maze (BM) and recognition memory by Novel Object Recognition test (NOR). We also assessed the effect of intravenous (iv) administration, as a non-invasive route, of hMSC on behavior and microgliosis in the dorsal hippocampus of AD rat model. Intact, STZ and STZ+MSC groups were used. After 24 days of STZ, when the damage was already established, animals received four times 1x106 MSC iv. We performed Open Field (OF), NOR, BM and Marble Burying (MB) tests to estimate memory, depression-like and anxiety-like behaviors. STZ group showed an increase in Iba1-immunoreactive microglial cells and a deficiency in all behavioral tests. STZ+MSC group improved its performance in OF, BM and MB. We concluded that MSC therapy is a suitable biological tool in neurodegenerative disorders, preventing the progression of cognitive impairment when injected in situ or restoring it when systemically administered for two months.