Amyloid precursor protein delays functional integration of adult-born hippocampal neurons.

MORGENSTERN NICOLÁS; GIACOMINI DAMIANA; LOMBARDI GABRIELA; SCHINDER ALEJANDRO

Huerta Grande, Córdoba

Congreso; Congreso anual de la Sociedad Argentina de Neurociencia (SAN); 2011

Sociedad Argentina de Neurociencias

The amyloid precursor protein (APP) has been largely implicated in impairment of synaptic transmission and plasticity in animal models of Alzheimer´s disease. We took advantage of adult neurogenesis to investigate the effects of cell-autonomous expression of beta-CTF, a cleavage product of APP, on functional and structural plasticity of hippocampal circuits in an otherwise healthy background. B-CTF was expressed together with a fluorescent reporter in neural progenitor cells of the adult mouse dentate gyrus by retroviral delivery. Morphological and functional connectivity of the neuronal progeny were analyzed after several days post infection (dpi). Expression of b-CTF induced a substantial reduction of glutamatergic afferent connectivity that was observed at 21 dpi but it was normalized by 35 days. This transient reduction in functional connectivity was paralleled by a decrease in dendritic length (with no changes in spine density) expressed at 21 but not 35 dpi. Thus, b-CTF appears to delay dendritic growth without altering synapse formation. Finally, similar defects in neuronal development were observed by retroviral expression of the non-amyloidogenic alpha-CTF. These results indicate that APP elicits a protracted dendritic development that is independent of Ab production.