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Hippocampal Neurofibromin and Amyloid Precursor Protein Expression in Dopamine D3 Receptor Knock-out Mice Following Passive Avoidance Conditioning

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Abstract

Passive avoidance (PA) conditioning is a fear motivated task able to initiate a cascade of altered gene expression within the hippocampus, a structure critical to learning and memory. We have previously shown that neurofibromin (NF1) and amyloid precursor protein (APP), two genes implicated in cognitive function, are differentially expressed in brain of dopamine D3 receptor knock-out mice (D3R−/−), suggesting that the receptor might have a role in their trascriptional regulation. Here in this study, we hypothesized that during acquisition of PA conditioning the expression of NF1 and APP genes could be influenced by D3Rs. To address this issue, we analyzed the expression of NF1 and APP in the hippocampus of both wild-type (WT) and D3R−/− mice subjected to the single trial step-through PA paradigm. Our finding demonstrated that (1) D3R−/− mice exhibit increased cognitive performance as compared to WT mice in the step-through PA trial; (2) acquisition of PA increased D3R and NF1, but not APP expression in WT mice hippocampus; (3) PA-driven NF1 induction in WT was abrogated in D3R−/− mice and finally that (4) the heightened basal APP expression observed in naive D3R−/− mice was totally reversed by acquisition of PA. In conclusion, the present finding show for the first time that both D3R and NF1 genes are upregulated following PA conditioning and suggest that hippocampal D3Rs might be relevant to NF1 transcriptional regulation in the hippocampus.

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Acknowledgments

These experiments were supported by the international PhD program in Neuropharmacology, University of Catania, Medical School. We thank Mr P. Asero for his technical support.

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Authors and Affiliations

  1. Department of Bio-Medical Sciences, Section of Anatomy and Histology, University of Catania, Via S. Sofia, 87, 95123, Catania, Italy

    Agata Grazia D’Amico, Alessandro Castorina & Velia D’Agata

  2. Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy

    Agata Grazia D’Amico, Gian Marco Leggio, Filippo Drago & Velia D’Agata

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  1. Agata Grazia D’Amico
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  2. Alessandro Castorina
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  3. Gian Marco Leggio
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  5. Velia D’Agata
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Correspondence to Velia D’Agata.

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D’Amico, A.G., Castorina, A., Leggio, G.M. et al. Hippocampal Neurofibromin and Amyloid Precursor Protein Expression in Dopamine D3 Receptor Knock-out Mice Following Passive Avoidance Conditioning. Neurochem Res 38, 564–572 (2013). https://doi.org/10.1007/s11064-012-0949-0

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  • DOI: https://doi.org/10.1007/s11064-012-0949-0

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