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

• Published in: Pharmacology, biochemistry and behavior Vol. 95; no. 4; pp. 485 - 493
• Main Authors: Ratia, M., Giménez-Llort, L., Camps, P., Muñoz-Torrero, D., Clos, MªV., Badia, A.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 01-06-2010; Elsevier
• Subjects: Acetylcholinesterase inhibitors; Aging; Amyloid precursor protein (APP); Biological and medical sciences; Huprine X; Learning and memory activation; Medical sciences; Mitogen activated protein kinase (MAPK); Neuropharmacology; Pharmacology. Drug treatments; Protein kinase Cα (PKCα); Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Learning and memory activation; Amyloid precursor protein (APP); Acetylcholinesterase inhibitors; Aging; Mitogen activated protein kinase (MAPK); Protein kinase Cα (PKCα); Huprine X; Senescence; Memory; Non-specific serine/threonine protein kinase; Activation; Learning; Acquisition process; Adult; Anticholinesterase agent; Behavior; Mechanism of action; Human; Middle age; Enzyme; Transferases; Rodentia; Mitogen-activated protein kinase; Amyloid precursor protein; Vertebrata; Mammalia; Mouse; Animal
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2010.03.013

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 α-secretase (ADAM10 and TACE/ADAM17) related to amyloid precursor protein (APP) processing remain to be established. In the present work, 12
month old 126/Sv
×
C57b/6 male mice which received chronic i.p. treatment with either saline, huprine X (0.04
µmol
kg
−
1) or huprine X (0.12
µmol
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.