Antidepressant-like effects exerted by the intranasal administration of a glucagon-like peptide-2 derivative containing cell-penetrating peptides and a penetration-accelerating sequence in mice |
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| Affiliation: | 1. Laboratory of Pharmacology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan;2. Laboratory of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan;3. Center for Translational Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan;4. Center for Drug Delivery Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan;1. Center for Psychiatric Neuroscience, Department of Psychiatry, University Medical Center, University of Lausanne, Prilly, Switzerland;2. Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Lausanne, Switzerland;3. Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia;4. Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland;1. Instituto de Química Médica (IQM-CSIC), E-28006 Madrid, Spain;2. Departamento de Biología de Sistemas, Universidad de Alcalá, E-28805 Alcalá de Henares, Madrid, Spain;3. Área de Farmacología, Departamento de Ciencias Biomédicas, Unidad Asociada Al IQM-CSIC, Universidad de Alcalá, E-28805 Alcalá de Henares, Madrid, Spain;1. Departments of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA;2. Pharmacology University of Pennsylvania, Philadelphia, PA 19104, USA;1. Department of Physiology, Shaoyang University, Shaoyang, Hunan, China;2. Department of Biochemistry and Molecular Biology, Basic Medical School, Shanxi Medical University, Taiyuan, China;3. Department of Biomed and Life Sciences, Lancaster University, Lancaster, UK;4. Department of Foreign Language, Shaoyang University, Shaoyang, Hunan, China |
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| Abstract: | The intracerebroventicular (i.c.v.) administration of glucagon-like peptide-2 (GLP-2) to rodents was shown to have antidepressant-like effects in imipramine-resistant depression-model mice. In order to utilize GLP-2 as a clinical treatment tool for depression, we herein focused on the intranasal delivery that is non-invasive approach, because the i.c.v. administration is invasive and impractical. In the present study, we prepared a GLP-2 derivative containing cell penetrating peptides (CPPs) and a penetration accelerating sequence (PAS) (PAS-CPPs-GLP-2) for the intranasal (i.n.) administration. PAS-CPPs-GLP-2 (i.n.) exhibited antidepressant-like effects in the forced-swim test (FST) and tail suspension test (TST) in naïve mice as well as adrenocorticotropic hormone (ACTH) treated-mice. However, PAS-CPPs-GLP-2 (i.v.) and the GLP-2 derivative containing CPPs without a PAS (CPPs-GLP-2) (i.n.) did not affect the immobility time in the mouse FST. Moreover, fluorescein isothiocyanate (FITC)-labeled PAS-CPPs-GLP-2 (i.n.), but not FITC-labeled CPPs-GLP-2 (i.n.) was distributed through the mouse brain after the FST session. These results suggest that PAS-CPPs-GLP-2 is effective for i.n. delivery to the brain, and may be useful in the clinical treatment of major depression. |
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| Keywords: | Glucagon-like peptide-2 Antidepressant Intranasal administration Brain drug delivery and targeting |
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