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Effects of Cerebrolysin™ on neurogenesis in an APP transgenic model of Alzheimer’s disease

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Abstract

Cerebrolysin (CBL) is a peptide mixture with neurotrophic effects that might reduce the neurodegenerative alterations in Alzheimer’s disease (AD). We have previously shown that in the amyloid precursor protein (APP) transgenic (tg) mouse model of AD, CBL improves synaptic plasticity and behavioral performance. However, the mechanisms are not completely clear. The neuroprotective effects of CBL might be related to its ability to promote neurogenesis in the hippocampal subgranular zone (SGZ) of the dentate gyrus (DG). To study this possibility, tg mice expressing mutant APP under the Thy-1 promoter were injected with BrdU and treated with CBL for 1 and 3 months. Compared to non-tg controls, vehicle-treated APP tg mice showed decreased numbers of BrdU-positive (+) and doublecortin+ (DCX) neural progenitor cells (NPC) in the SGZ. In contrast, APP tg mice treated with CBL showed a significant increase in BrdU+ cells, DCX+ neuroblasts and a decrease in TUNEL+ and activated caspase-3 immunoreactive NPC. CBL did not change the number of proliferating cell nuclear antigen+ (PCNA) NPC or the ratio of BrdU+ cells converting to neurons and astroglia in the SGZ cells in the APP tg mice. Taken together, these studies suggest that CBL might rescue the alterations in neurogenesis in APP tg mice by protecting NPC and decreasing the rate of apoptosis. The improved neurogenesis in the hippocampus of CBL-treated APP tg mice might play an important role in enhancing synaptic formation and memory acquisition.

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Acknowledgments

This work was supported by NIH grant AG05131 and by a grant from EBEWE Pharmaceuticals.

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Authors and Affiliations

  1. Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA, 92093-0624, USA

    Edward Rockenstein, Michael Mante, Anthony Adame & Eliezer Masliah

  2. Department of Pathology, University of California San Diego, School of Medicine, La Jolla, CA, 92093-0624, USA

    Leslie Crews & Eliezer Masliah

  3. Research Division, EBEWE Pharmaceuticals, Unterach, Austria

    Herbert Moessler

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  1. Edward Rockenstein
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  2. Michael Mante
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Correspondence to Eliezer Masliah.

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Rockenstein, E., Mante, M., Adame, A. et al. Effects of Cerebrolysin™ on neurogenesis in an APP transgenic model of Alzheimer’s disease. Acta Neuropathol 113, 265–275 (2007). https://doi.org/10.1007/s00401-006-0166-5

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