Windows into estradiol effects in Alzheimer's disease therapy.

BACKGROUND AND OBJECTIVES

Alzheimer's disease (AD) is a neurological disorder associated with aging. The neuropathologic features of this disease are senile plaques and neurofibrillary tangles, which are present in memory structures and cerebral cortex. This study focuses on evaluation of estradiol administration in the management of neurological changes accompanied with AD in ovariectomized rats intoxicated with aluminum.

MATERIALS AND METHODS

Fifty adult female rats were classified into 5 main groups as follows: Group (1): gonad intact control, Group (2): ovariectomized control group, Group (3): ovariectomized rats were injected subcutaneously with estradiol for 18 weeks, Group (4): ovariectomized rats were injected intraperitoneally with aluminum chloride (AlCl3) daily for three months, Group (5): ovariectomized rats were injected intraperitoneally with AlCl3 for three months, then, they were injected subcutaneously with estradiol three times weekly for 18 weeks. Hydrogen peroxide (H2O2), malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), B cell lymphoma 2 (Bcl-2), brain derived neurotrophic factor (BDNF), acetylcholinesterase (AchE) and acetylcholine (Ach) were determined in brain tissue of all studied groups.

RESULTS

The results showed that brain TAC, SOD activity, Bcl-2 and BDNF levels were decreased significantly due to ovariectomy. Brain H2O2, MDA levels and AchE activity were increased significantly after AlCl3 administration to ovariectomized rats. Brain TAC, Bcl-2, BDNF and Ach levels were decreased significantly as a result of AlCl3 supplementation to ovariectomized rats. Treatment of rats with estradiol produced marked improvement in the most studied biomarkers and this finding was well documented by histological investigation of the brain which showed remarkable improvement in the feature of the neurons in addition to the disappearance of plaques.

CONCLUSIONS

We could conclude that estradiol administration significantly ameliorates the neurodegeneration characteristic of Alzheimer's disease in experimental rat model. This may be attributed to its powerful antioxidant, antiapoptotic, neurotrophic as well as its antiamyloidogenic activities.