The Effect of BSA-Based Curcumin Nanoparticles on Memory and Hippocampal MMP-2, MMP-9, and MAPKs in Adult Mice Roksana SoukhakLari 1 & Leila Moezi 2,3 & Fatema Pirsalami 3 & Maryam Moosavi 2,4 Received: 5 May 2018 /Accepted: 14 June 2018 /Published online: 24 June 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract Although high rate of curcumin consumption has been suggested to decrease the prevalence of Alzheimer’ s disease (AD), its administration has no effect on the progression of AD in humans and this has been attributed to its poor bioavailability. Using nanotechnology to break down curcumin increases its bioavailability and improves its effect on the brain. BSA, as a non-toxic protein with high binding capacity, was used to break curcumin to nanosize and to explore the effect of nanocurcumin on passive avoidance memory and hippocampal MMP-2 and -9 and MAPKs. BSA-based nanocurcumin was produced by desolvation method. In this study, 15 and 20 mg/kg/p.o. nanocurcumin (based on our preliminary studies) were administered to male NMRI mice weighing 20–25 g for 10 days. Passive avoidance training was performed on day 10 and 24 h after, a retention trial was done. Upon completion of behavioral studies, the hippocampi were isolated and western blot analysis was performed on MMP-2, MMP-9, and MAPKs (JNK, ERK, and p38). The results showed that BSA-based nanocurcumin administered at 15 and 20 mg/kg doses resulted in a significantly improved performance in passive avoidance memory test while its equivalent doses of natural curcumin did not produce a similar effect. In addition, this effect was accompanied with an increase in MMP-2, MMP-9, and p- ERK and a decrease in p-JNK. This study indicates that breaking curcumin to nanosize produces improved effects on passive avoidance memory in adult mice accompanied with MMP-2, MMP-9, p-ERK, and p-JNK changes in the hippocampus. Keywords Nanocurcumin . Curcumin . Memory . Hippocampus . MMP . MAPKs Introduction It has been suggested that there is a correlation between curry consumption and cognitive performance, as it has been reported that individuals who occasionally and often consume curry per- form better on MMSE (Mini –Mental State Examination) as com- pared with those who never or rarely eat curry (Ng et al. 2006). Curcumin, the main ingredient in turmeric, exhibits some neuro-protective effects on a variety of nervous system damages. In spite of some reports indicating its beneficial effect in animal models of Alzheimer’ s disease (AD), oral curcumin administration (2 or 4 g/day) in AD patients did not alter the disease’ progression as compared to the placebo (Baum et al. 2008; Ringman et al. 2012). The low bioavail- ability feature of curcumin and its poor absorption from the intestine are the supposed reasons for this inefficacy (Anand et al. 2007; Witkin et al. 2013). In line with these, a solid lipid curcumin formulation, which is about 65 times more bioavail- able than natural curcumin (Gota et al. 2010), has been shown to improve mood and cognition in healthy human adults (Cox et al. 2015). Thus, it seems that increasing the bioavailability of curcumin improves its effect on cognitive function. Matrix metalloproteinase 2 and 9 (MMP-2 and -9) have been suggested to play roles in AD pathology (Brkic et al. 2015) as their circulating levels increase in this disease (Duits et al. 2015; Lorenzl et al. 2003). It has been shown that beta amyloid accumulation leads to increases in MMP-2 and MMP-9 (Fujimoto et al. 2008). Additionally, MMP inhibitor II prevents beta amyloid-induced neuronal cell death (Haorah et al. 2007). However, MMP-2 and -9 have been suggested to * Maryam Moosavi marmoosavi@sums.ac.ir 1 Students Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 2 Nanobiology and Nanomedicine Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran 3 Department of Pharmacology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran 4 Shiraz Neuroscience Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran Journal of Molecular Neuroscience (2018) 65:319–326 https://doi.org/10.1007/s12031-018-1104-4