INVESTIGADORES
GARCIA Mariana Gabriela
congresos y reuniones científicas
Título:
Intravenous mesenchymal stem cells administration as a neuroprotective therapy in a rat model of sporadic alzheimer's disease
Autor/es:
ZAPPA VILLAR MF; LOPEZ HANOTTE J; PARDO J; MOREL GR; GARCIA M; REGGIANI P
Reunión:
Congreso; Society for Neuroscience 48th Annual Meeting; 2018
Resumen:
Alzheimer's disease (AD) is the most prevalent neurodegenerative pathology with no efficient therapy. The signaling pathways that become defective, altering the normal protein homoeostasis of amyloid β-peptide (Aβ) and tau protein, and thus initiating a series of pathophysiological responses ultimately causing synaptic loss and cognitive decline, are unclear and much sought after. Our objective is to develop therapeutic strategies that allow preventing and/or overcoming the degenerative changes in the brain with experimental AD. In this context, cell therapy emerges as a promising therapeutic approach. We set up a model of sporadic AD by the intracerebroventricular (icv) injection of streptozotocin (STZ) in rats. In a first study, we evaluated behavior and gliosis in the dorsal hippocampus of STZ-injected rats after 24 days. We assessed learning and spatial memory by the Barnes Maze (BM) and anxiety-related behavior by the Marble Burying (MB) test. STZ-treated rats exhibited impairments in these tests as compared with control counterparts. Furthermore, STZ rats displayed Stratum Radiatum (SR) volume reduction and a decreased NeuN immunoreactivity (neuron loss) in the hippocampal CA1 region, together with an increased immunoreactivity for the microglial (Iba1) and astroglial (GFAP) markers (neuroinflammation).In another experimental approach, we assessed the effect of intravenous administration (as a non-invasive route) of Human Umbilical Cord Mesenchymal Stem Cells (HUC-MSC) on cognitive performance in the AD rat model. Three experimental groups were used: intact, STZ, and STZ+MSC. After 24-day STZ injection, when the damage was already established, animals received every 18 days, a suspension of 1x106 HUC-MSC in a tail vein. During the last two weeks until the end of the study we performed Open Field, BM, and MB tests to estimate memory, depression-like, and anxiety-like behaviors. STZ treated rats were deficient in all behavioral tests and morphological assessment. STZ+MSC group increased exploratory frequency in the Open Field test. Moreover, these animals showed an improvement in their spatial memory performance in the BM. Anxiety-like behavior in the MB test was also attenuated by exposure to MSC. Interestingly, MSC therapy restored hippocampal atrophy in the SR region and ameliorated neuron loss. Additionally, decreased microgliosis and astrogliosis was observed in the MSC-treated rats.We conclude that MSCs therapy is a suitable biological tool in neurodegenerative disorders, restoring the progression of cognitive impairment and neuroinflammation when systemically administered for more than two months.