Intranasal Delivery of Plasma and Platelet Growth Factors Using PRGF-Endoret System Enhances Neurogenesis in a Mouse Model of Alzheimer’s Disease

Abstract

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.

PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells

“…2 and 4). Similar anti-apoptotic effects of PRGF technology have been previously reported on a mouse model of Alzheimer's disease [27,28].…”

Intranasal PRGF-Endoret enhances neuronal survival and attenuates NF-κB-dependent inflammation process in a mouse model of Parkinson's disease

“…In addition, we demonstrated that PRGF-Endoret appears to possess an inherent NF-kB-mediated antiinflammatory function in this AD model [27]. Most interestingly, PRGF-Endoret acts as neurotrophic factor promoting neuronal survival under amyloid beta (A) exposure [28].…”

“…One previous study showed that PRGF-Endoret enhances hippocampal neurogenesis after intranasal application in a mouse model of AD [28], and very recently, PRGFEndoret proved to be neuroprotective in transgenic APP/PS1 mice, with multifunctional and complementary effects that result in the reversal of the broad range of cognitive deficits in AD [27]. PRGF-Endoret constitutes a biological system that provides a complex pool of growth factors that may stimulate and accelerate tissue regeneration [20].…”

“…Regulation of NF-B activity by autologous-activated platelet-rich plasma helping to suppress inflammation has been described in chondrocytes [24,25], and mesenchymal stem cells [26]. Very recently, we have reported a new intranasal delivery system with PRGF-Endoret which allowed neurodegeneration reversion and memory rescue in a transgenic mouse model of Alzheimer's disease (AD) [27,28]. In addition, we demonstrated that PRGF-Endoret appears to possess an inherent NF-kB-mediated antiinflammatory function in this AD model [27].…”

Application of APP/PS1 Transgenic Mouse Model for Alzheimer’s Disease

“…It is indicated that hippocampal neurogenesis may increase during the development of AD [57]. It is suggested that neurogenesis in APP/PS1 mice might be a compensatory effect for pathologic changes, and AD brain tissue may exist some toxic factors on neurogenesis [58]. Therefore, it is necessary to give some appropriate stimulus for the neurogenesis of neurons.…”