Neurodegeneration together with a reduction in neurogenesis are cardinal features of
Alzheimer's disease (AD) induced by a combination of toxic
amyloid-β
peptide (Aβ) and a loss of trophic factor support. Amelioration of these was assessed with diverse
neurotrophins in experimental therapeutic approaches. The aim of this study was to investigate whether intranasal delivery of plasma rich in
growth factors (PRGF-Endoret), an autologous pool of morphogens and
proteins, could enhance hippocampal neurogenesis and reduce neurodegeneration in an
amyloid precursor
protein/
presenilin-1 (APP/PS1) mouse model. Neurotrophic and neuroprotective actions were firstly evident in primary neuronal cultures, where cell proliferation and survival were augmented by Endoret treatment. Translation of these effects in vivo was assessed in wild type and APP/PS1 mice, where neurogenesis was evaluated using
5-bromodeoxyuridine (BdrU), doublecortin (DCX), and NeuN immunostaining 5 weeks after Endoret administration. The number of
BrdU, DCX, and NeuN positive cell was increased after chronic treatment. The number of degenerating neurons, detected with
fluoro Jade-B staining was reduced in Endoret-treated APP/PS1 mice at 5 week after
intranasal administration. In conclusion, Endoret was able to activate neuronal progenitor cells, enhancing hippocampal neurogenesis, and to reduce Aβ-induced neurodegeneration in a mouse model of AD.