A Novel 1,4-Dihydropyridine Derivative Improves Spatial Learning and Memory and Modifies Brain Protein Expression in Wild Type and Transgenic APPSweDI Mice |
| |
| Authors: | Baiba Jansone Inga Kadish Thomas van Groen Ulrika Beitnere Doyle Ray Moore Aiva Plotniece Karlis Pajuste Vija Klusa |
| |
| Institution: | 1. Department of Pharmacology, Faculty of Medicine, University of Latvia, Riga, Latvia.; 2. Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; 3. Department of Pharmacology/Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; 4. Latvian Institute of Organic Synthesis, Riga, Latvia.; Hungarian Academy of Sciences, HUNGARY, |
| |
| Abstract: | Ca2+ blockers, particularly those capable of crossing the blood-brain barrier (BBB), have been suggested as a possible treatment or disease modifying agents for neurodegenerative disorders, e.g., Alzheimer’s disease. The present study investigated the effects of a novel 4-(N-dodecyl) pyridinium group-containing 1,4-dihydropyridine derivative (AP-12) on cognition and synaptic protein expression in the brain. Treatment of AP-12 was investigated in wild type C57BL/6J mice and transgenic Alzheimer’s disease model mice (Tg APPSweDI) using behavioral tests and immunohistochemistry, as well as mass spectrometry to assess the blood-brain barrier (BBB) penetration. The data demonstrated the ability of AP-12 to cross the BBB, improve spatial learning and memory in both mice strains, induce anxiolytic action in transgenic mice, and increase expression of hippocampal and cortical proteins (GAD67, Homer-1) related to synaptic plasticity. The compound AP-12 can be seen as a prototype molecule for use in the design of novel drugs useful to halt progression of clinical symptoms (more specifically, anxiety and decline in memory) of neurodegenerative diseases, particularly Alzheimer’s disease. |
| |
| Keywords: | |
|
|
