p19INK4d avoids DNA damage-induced neurodegeneration in mice hippocampus and prevents loss of cognitive functions

OGARA M.F.; BELLUSCIO L.M.; DE LA FUENTE V.; BERARDINO B.G.; FERRONI N.M.; SONZOGNI S.V.; CANEPA E.T.

Huerta Grande - Córdoba

Congreso; XXVIII CONGRESO DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN NEUROCIENCIAS (SAN); 2013

SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN NEUROCIENCIAS (SAN)

Defects in DNA repair have been linked to cognitive decline with age and neurodegenerative diseases, yet the mechanisms that protect neurons from genotoxic stress remain largely unknown. There are strong evidences that p19INK4d (p19), a member of the INK4-cell cycle inhibitor family, plays a crucial role in regulating genomic stability and cell survival in neuron primary cultures from rat hippocampus. In this work, we sought to examine whether the neuroprotective properties of p19 could be recapitulated in an in vivo mouse model. To do this, 0.5 nmol ss-DNA oligonucleotide containing an antisense sequence of p19 was laterally injected by stereotaxis in the dorsal hippocampus to selectively knockdown the p19 expression, after which 25 ng/ml NCS or saline solution was administered in each hippocampus. Brain sections were examined for gammaH2AX to label DNA damaged cells. gammaH2AX-positive cells in hippocampus from mice previously injected with p19 antisense (48.9±9.3%) was significantly increased (p