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P2‐388: 17‐beta‐estradiol: A potential therapeutic drug for Alzheimer's disease
Author(s) -
Kumar Pardeep,
Kale R.K.,
Baquer Najma
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.1098
Subject(s) - monoamine oxidase , medicine , neurodegeneration , endocrinology , neuroprotection , dementia , disease , estrogen , hormone , chemistry , enzyme , biochemistry
Background: Alzheimer’s disease (AD) is the most common form of dementia in the elderly. AD is characterized by the presence of amyloid plaques which are formed from deposits of b-amyloid protein (Ab). Accumulation of oligomeric Ab in the brain contributes to neuronal dysfunction and ultimately leads to neurodegeneration. During aging the brain experiences structural, molecular, and functional alterations. These changes increase during menopausal condition in females when the level of estradiol is decreased. Recently, there has been a growing interest in the action and functions of the ovarian steroid hormone estradiol, particularly on whether they are neuroprotective for such age related disease and neurodegenerative conditions like stroke, Parkinson’s disease and AD. The objective of this study was to investigate protective potential of 17b estradiol (E2) treatment on the activity of monoamine oxidase, calcium homeostasis, membrane polarization, genomic DNA degradation, 4hydroxynonenal and protein oxidation levels occurring in brains of female rats of 3 months (young), 12 months (adult) and 24 months (old) age groups, and to see whether these changes are restored to normal levels after exogenous administration of estradiol. Methods: The aged rats (12 and 24 months old) (n 1⁄4 8 for each group) were given subcutaneous injection of 17 b -estradiol (0.1 mg/g body weight) daily for one month. After 30 days of hormone treatment, experimental animals of all the groups were sacrificed and brains were isolated for further study. Results: The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, calcium homeostasis, genomic DNA degradation, 4hydroxynonenal and protein oxidation levels in the brains of aging female rats, and a decrease in membrane polarization. Our data showed that exogenous administration of E2 brought these changes to near normalcy in aging female rats. Conclusions: It can therefore be concluded that E2’s beneficial effects seemed to arise from its, antioxidant and antilipid peroxidative effects, implying a therapeutic potential drug for age related changes. Based on our studies and others, we conclude that E2 have therapeutic potential for adjunctive therapy along with dopamine replacement in AD.