IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Amyloid precursor protein delays functional integration of adult-born hippocampal neurons
Autor/es:
DAMIANA GIACOMINI; NICOLÁS MORGENSTERN; GABRIELA LOMBARDI; ALEJANDRO SCHINDER
Lugar:
Lisboa
Reunión:
Simposio; Champalimaud Neuroscience Symposium 2012; 2012
Institución organizadora:
Champalimaud Foundation
Resumen:
Alzheimer´s disease (AD) is a neurodegenerative disorder that is identified by the extracellular accumulation of abnormally folded B-amyloid peptide (AB) in the cerebral cortex and hippocampus. The amyloid precursor protein (APP), the precursor molecule of AB, has been largely implicated in impairment of synaptic transmission and plasticity in animal models of AD. Taking advantage of adult neurogenesis, we have expressed different forms of APP to investigate their effects on functional and structural plasticity in newly generated hippocampal neurons in an otherwise healthy background. Human APP (hAPP) variants were expressed together with a fluorescent reporter in neural progenitor cells of the dentate gyrus of mice by retroviral delivery. Morphological and functional connectivity of the neuronal progeny were analyzed after several days post infection (dpi). Neurons expressing B-CTF, a cleavage product of APP, exhibited a substantial reduction of glutamatergic afferent connectivity at 21 dpi that it was normalized by 35 days. This transient functional alteration was paralleled by a decrease in dendritic length (with no changes in spine density) expressed at 21 but not 35 dpi. Thus, B-CTF delays dendritic growth without altering synapse formation. Finally, similar defects in neuronal development were observed by retroviral expression of alpha-CTF, a non-amyloidogenic fragment of hAPP. These results indicate that APP elicits a protracted dendritic development that is independent of AB production.