Behavioural effects and regulation of PKCalpha and MAPK by huprine X in middle aged mice.

Abstract

The behavioural effects of huprine X, a new anticholinesterasic inhibitor, as well as its effects on the regulation of protein kinase C (PKC), mitogen activated protein kinase (MAPK) and alpha-secretase (ADAM10 and TACE/ADAM17) related to amyloid precursor protein (APP) processing remain to be established. In the present work, 12 month old 126/SvxC57b/6 male mice which received chronic i.p. treatment with either saline, huprine X (0.04 micromol kg(-1) or huprine X (0.12 micromol kg(-1), were submitted to a battery of behavioural tests and thereafter the brains were dissected to study the neurochemical effects induced by huprine X. The results show that, in a dose dependent manner, huprine X facilitates learning and memory in the Morris water maze and improves some indicators of emotionality without inducing adverse effects, affecting motor activity nor anxiety-like behaviours, as measured in the open-field and corner tests. Moreover activation of downstream PKC/MAPK signaling pathways may underly these behavioural effects as well as the stimulation of the non-amyloidogenic processing of APP. Results obtained herein using a sample of aged animals strongly suggest that huprine X constitutes a promising therapeutic agent for the treatment of cholinergic dysfunction underlying aging and/or dementias.

• Authors: M Ratia, L Giménez-Llort, P Camps, D Muñoz-Torrero, M V Clos, A Badia
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 95 Issue 4 Pg. 485-93 (Jun 2010) ISSN: 1873-5177 [Electronic] United States
• PMID: 20363245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Aminoquinolines
• Amyloid beta-Protein Precursor
• Cholinesterase Inhibitors
• Heterocyclic Compounds, 4 or More Rings
• Membrane Proteins
• huprine X
• Prkca protein, mouse
• Protein Kinase C-alpha
• Mitogen-Activated Protein Kinases
• Amyloid Precursor Protein Secretases
• ADAM Proteins
• ADAM10 Protein
• Adam10 protein, mouse
• ADAM17 Protein
• Adam17 protein, mouse

Topics

• ADAM Proteins (metabolism)
• ADAM10 Protein
• ADAM17 Protein
• Aging
• Aminoquinolines (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Amyloid Precursor Protein Secretases (metabolism)
• Amyloid beta-Protein Precursor (metabolism)
• Animals
• Behavior, Animal (drug effects)
• Cerebral Cortex (drug effects, metabolism)
• Cholinesterase Inhibitors (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Heterocyclic Compounds, 4 or More Rings (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Hippocampus (drug effects, metabolism)
• Learning (drug effects)
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinases (metabolism)
• Motor Activity (drug effects)
• Protein Kinase C-alpha (metabolism)
• Protein Transport (drug effects)
• Random Allocation
• Signal Transduction (drug effects)
• Time Factors