Empty and loaded NBVs were used in presence and not of Aβ 1-42 and Aβ 1-42 scrambled. As a control, we tested the effect of Aβ 1-42 with a scrambled sequence (200 nM).

In vitro Alzheimer model were obtained applying Aβ 1-42 oligomers (200 nM). An additional recording of baseline was evaluated before inducing Long-Term Potentiation by theta-burst stimulation and responses (fEPSP) were recorded for 1h. Paired pulse facilitation was assessed at inter-stimulus intervals ranging from 50 to 500 ms. The electrophysiological experiments were conducted using C57BL6/J mice of both sexes aged between 30 and 40 days. In vitro FUS analysis were performed to evaluate the ability of FUS to induce a stable and prolonged release of EA. Method: Empty and loaded NBVs were prepared and deeply characterized. The EA will be loaded inside the vesicles and their neuroprotective effect will be explored using electrophysiological recordings (field and whole cell patch clamp) of hippocampal synaptic transmission and plasticity in ex-vivo Alzheimer model. A valid approach could be delivering the drug in non-ionic surfactant vesicles (NBVs) through the nose to brain (N2B) route coupled to focused ultrasound (FUS) improving brain targeting. Additionally, current proteomic data analysis aims at unraveling differentially modulated signaling pathways in APP/PS1 compared to WT ahNPC.īackground: Ellagic acid (EA) has been shown to have protective effects in Alzheimer's disease, but it shows poor pharmacokinetic profile.

Studies are ongoing to assess PEP3 in vivo effects on immature neurons and to identify ADAM10 targets involved in PEP3- mediated modulation of ahNPC neuronal fate specification. These results suggest that PEP3 may exert novel activities on ahNPC, potentially contributing to its pro-cognitive effects. Preliminary data obtained in a proximity ligation assay confirmed that pro-neurogenic PEP3 concentrations reduced ADAM10/AP2 interaction in WT ahNPC. PEP3 treatment promoted neuronal differentiation in both genotypes, but more significantly in APP/PS1 ahNPC. NPCs were treated with PEP3 or an inactive peptide for 24 h. Under basalĬonditions, we observed a reduced ability of APP/PS1-derived ahNPC to generate neurons, compared to their WT counterpart. Progenitors, cells isolated from WT and APP/PS1 mice could represent in vitro models to investigate consequences of disrupted ADAM10-dependent pathways. Since immunoprecipitation confirmed ADAM10/AP2 interaction in adult hippocampal To restore this alteration, a cell-permeable peptide (PEP3) disrupting the interaction between ADAM10 and AP2 has been developed and proven, under subchronic treatment, to rescue synaptic and cognitive impairment in 6-7 month-old APP/PS1 mice (3). One protein expressed in immature neurons is ADAM10, an enzyme involved in non-Īmyloidogenic Amyloid Precursor Protein (APP) processing and in dendritic spine shaping.Ĭompared to healthy controls, in AD hippocampi ADAM10 membrane expression is reduced due to its increased endocytosis, mediated by AP2 interaction (2). Altogether disrupted adult neurogenesis, an early defect in AD, can be regarded as a potential contributor to AD pathophysiology.

It has been demonstrated that adult-born hippocampal immature neurons (DCX + cells) can be recruited into the engram but their functional role is defective in AD animal models (1). Alzheimer’s disease (AD) is a neurodegenerative disease with progressive memory loss and severe cognitive deficits.Īdult hippocampus harbors neural progenitor cells (ahNPCs).

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