Alteration in memory cognition due to activation of caveolin-1 and oxidative damage in a model of dementia of Alzheimer's type.

Abstract

OBJECTIVE:The present study aims to investigate the role of caveolin-1 in dementia of Alzheimer's type using intracerebroventricular streptozotocin (ICV-STZ)-induced neurodegeneration model in rats.MATERIALS AND METHODS:Male Wistar rats (220–260 g) were employed. STZ 3 mg/kg via ICV route was given once to cause neuronal injury. Daidzein – a caveolin inhibitor at 0.2, 0.4, and 0.6 mg/kg s.c. were given daily whereas minoxidil – a caveolin activator was given at 0.45 mg/kg, i.p. on alternate days for 28 days. STZ was also given at its submaximal dose 1.5 mg/kg to minoxidil group only.RESULTS:ICV-STZ control animals exhibited cognitive and neurological deficits on the Morris water maze, elevated plus maze, and balance beam tests (P < 0.0001). Treatment with daidzein significantly restored memory impairments and decreased oxidative damage whereas minoxidil potentiates the effect of STZ causing significant impairment in memory. Significant oxidative stress such as lipid peroxidation and glutathione (P < 0.0001) were also observed due to ICV-STZ administration resulting in neuronal damage which was significantly prevented by treatment with daidzein in brain tissues.CONCLUSION:The findings from the present investigation may conclude that the caveolin-1 from caveolae at the cell membrane induces memory deficits and oxidative stress phenotype that resemble the neurological phenotype of Alzheimer's disease. Further studies are warranted to gauge the effect of caveolin dyshomeostasis on the amyloidogenic cascade.