Early neuroglial and cognitive impairment before amyloid deposition in young PDAPP-J20 transgenic mice, model of Alzheimer's disease.

POMILIO C; BEAUQUIS J; VINUESA A; PAVÍA P; SARAVIA F

Huerta Grande, Córdoba

Congreso; Congreso Anual de la Sociedad Argentina de Neurociencias (SAN); 2013

Sociedad Argentina de Investigación en Neurociencias

The Alzheimer's disease (AD) is the most common form of dementia and is characterized in late stages by widespread amyloid deposition and neurodegeneration in the hippocampus but less is known about early brain and behavioral alterations. We evaluated neuroglial alterations in PDAPP-J20 mice (Tg), model of AD, at 5 months of age, an early stage when no amyloid plaques are present. The hippocampus of Tg mice showed a significant decrease in the number of neurons in the dentate gyrus and CA1 subfield. Additionally, mature granular neurons exhibited signs of cell atrophy. Neurogenic capability was also affected in Tg mice: the number of newborn DCX+ granule cells was reduced, along with differed maturation. In stratum radiatum under CA1, young Tg mice showed a diminution in the number of astrocytes compared to control group, analyzed by confocal microscopy and 3D reconstruction. Astroglia was morphologically altered presenting a decline in surface/volume ratio, analyzed by confocal microscopy and 3D reconstruction. Glial changes could reflect less support to neurons. These morphostructural alterations were associated with cognitive impairment at this initial stage of AD. The performance in the novel object location recognition test suggested that the spatial memory of Tg mice was affected. In summary, these results focalize in early neuronal, astroglial and cognitive alterations in AD, which can be proposed in the future as potential therapeutic and diagnostic targets.