Piracetam ameliorates Aß induced impairment of neuritic outgrowth
In agreement with the pronounced loss of neurites and synapses in AD brain as one of the functionally most relevant histopathological lesions (Selkoe, 2002; Lacor et al., 2007), Aß peptides have been repeatedly demonstrated to reduce neuritic outgrowth in different neuronal cell lines in vitro including PC12 cells (Hirata et al., 2005; Hu et al., 2007; Evans et al., 2008). Oligomeric Aß seems to be more active than fibrillar Aß (Lacor et al., 2007; Evans et al., 2008). In agreement with these observations, the addition of oligomeric Aß1–42 (1 μM) to nerve growth factor (NGF) treated PC12 cells reduces neuritic length significantly. When the same experiment was carried out in the presence of piracetam (1 mM), the negative effect of oligomeric Aß1–42 was completely inhibited. In agreement with the assumption that enhanced oxidative stress might explain the Aß induced reduction of neuritic outgrowth (Guglielmotto et al., 2009) treating PC12 cells with SNP reduced neuritic outgrowth even stronger. Again, piracetam ameliorates this negative effect significantly under conditions of optimal NGF stimulation (Figure 4). A reduction of neuritic outgrowth depending on Aß load was also observed in our PC12 cells transgenic for human APP, where we observed a reduction of neuritic length, which could be substantially ameliorated by piracetam (Figure 4). The enhancing effect of piracetam was observed over the whole NGF concentration range (1–50 ng/ml) still leading to increased neuritic length under maximum NGF stimulation (Figure 4).
Figure 4  Piracetam improves neuritogenesis following Aß exposure. (A) PC12 cells were treated over 6 days with NGF 50 ng/ml in the presence of oligomeric Aβ 1 μM. Piracetam 1 mM was added and the effects on neurite outgrowth were investigated. (B) APPsw PC12 cells were treated over 6 days with NGF 50 ng/ml in the presence or absence of piracetam 1 mM and neurite outgrowth was measured. In the presence of different NGF concentrations (1–50 ng/ml) piracetam improved the neurotrophic effect of NGF in APPsw cells. All data are modified after Kurz et al. (2010). Data are expressed as mean ± SEM (n = 6–7) **p < 0.01, ***p < 0.001 vs. the respective control, two-way anova with bonferroni post test.