INVESTIGADORES
SARAVIA Flavia Eugenia
congresos y reuniones científicas
Título:
Early astroglial and neuronal changes in the hippocampus of PDAPP-J20 transgenic mice, model of Alzheimer's disease.
Autor/es:
BEAUQUIS J; POMILIO C; VINUESA A; PAVIA P; GALVAN V; SARAVIA F
Lugar:
San Diego
Reunión:
Congreso; Society for Neuroscience Meeting; 2013
Institución organizadora:
SfN
Resumen:
In the context of Alzheimer?s disease (AD), hippocampal alterations have been
well described in advanced stages of the pathology, when widespread amyloid
pathology is present and inflammatory changes and glial reactivity occur, but
less attention has been directed to study early brain changes. In the present
study, using an animal model of AD, the transgenic PDAPP-J20 mouse
(carrying human APP gene with Swe and Ind familial AD mutations), we studied
early alterations in astroglia and neurons. We evaluated transgenic (Tg) and
control (NTg) mice at 5 months of age, when no amyloid plaques are present in
the hippocampus and low cerebral levels of amyloid peptides are detectable.
Astrocytes were studied using glial fibrillary acidic protein (GFAP)
immunofluorescence, confocal imaging and stereology. In Tg mice, we found a
reduction in the number of GFAP+ astrocytes in CA1 region along with a
decrease in astrocytic three-dimensional complexity studied as a
surface/volume index, contrasting the established notion of a generalized
astrogliosis accompanying the neurodegenerative process. Regarding neuronal
changes, we found significantly less number of NeuN+ neurons in CA1
pyramidal layer of Tg mice but no changes were detected in dendritic spine
density studied by means of a Golgi study. We also analyzed the number and
morphology of doublecortin+ (DCX) cells in the dentate gyrus to evaluate adult
neurogenesis. Transgenic animals showed decreased numbers of DCX+ cells
showing a mature as well as an immature morphology, although Tg animals had
a relative shift towards a more mature morphology to the detriment of the
immature population. These changes in adult-born neurons in the dentate gyrus
correlated with a decrease in the expression of synaptophysin+ mossy fibers
reaching CA3. Our data support the idea of premature loss of both neurons and
astrocytes in the hippocampus of AD mice at an age when there are no
evidences of extensive amyloid pathology. Both cell types appear as especially
vulnerable at early stages of the pathology. Astroglial changes found in this
study characterize an atrophic phenotype and a lost of glial support could
explain the neuronal changes found at this age, although a primary neuronal
alteration cannot be discarded.