Meloxicam-loaded nanocapsules as an alternative to improve memory decline in an Alzheimer's disease model in mice: involvement of Na(+), K(+)-ATPase.

ABSTRACT

The objective of this study was to investigate the effect of meloxicam-loaded nanocapsules (M-NC) on the treatment of the memory impairment induced by amyloid ß-peptide (aß) in mice. The involvement of Na(+), K(+)-ATPase and cyclooxygenase-2 (COX-2) activities in the hippocampus and cerebral cortex was also evaluated. Mice received aß (3 nmol/ 3 µl/ per site, intracerebroventricular) or vehicle (3 µl/ per site, i.c.v.). The next day, the animals were treated with blank nanocapsules (17 mL/kg) or M-NC (5 mg/kg) or free meloxicam (M-F) (5 mg/kg). Treatments were performed every other day, until the twelfth day. Animals were submitted to the behavioral tasks (open-field, object recognition, Y-maze and step-down inhibitory avoidance tasks) from the twelfth day. Na(+), K(+)-ATPase and COX-2 activities were performed in hippocampus and cerebral cortex. aß caused a memory deficit, an inhibition of the hippocampal Na(+), K(+)-ATPase activity and an increase in the hippocampal COX-2 activity. M-NC were effective against all behavioral and biochemical alterations, while M-F restored only the COX-2 activity. In conclusion, M-NC were able to reverse the memory impairment induced by aß, and Na(+), K(+)-ATPase is involved in the effect of M-NC.