Role of Estrogen Hormone in Lipopolysaccharide-Induced Alzheimer’s Disease in Female Rats; Possible Underlying Mechanisms and Modulation by Progesterone Hormone
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- Category: Vol. 82, March 2014
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Role of Estrogen Hormone in Lipopolysaccharide-Induced Alzheimer’s Disease in Female Rats; Possible Underlying Mechanisms and Modulation by Progesterone Hormone, MAHA M. GAMAL EL-DIN, ZEINAB A. AHMAD, MAHA ZEKRY and OMAIMA M. ABDEL WAHAB
Abstract
Alzheimer’s disease (AD) is a devastating neurodegener-ative disorder manifested by deterioration in memory and cognition, impairment in performing activities of daily living, and many behavioral and neuropsychiatric illnesses.
Aim of the work: To investigate the effect of estrogen hormone in AD and the possible modulation of estrogen effect by progesterone hormone and to clarify the underlying mech-anisms involved in this effect.
Methodology: The current study was conducted on 50 female albino rats weighing between 150-200gm divided into the following groups: Group I: (Control group): Animals of this group were trained and their behavioral assessment at zero time was done. Animals then were sham operated, and were injected with saline, Group II: (AD group): AD was induced in this group by injecting them with a single dose of LPS 0.8mg/kg i.p., Group III: (AD+OVX group): Animals underwent bilateral OVX. Four weeks after OVX, AD was induced as in group II, Group IV: (AD+OVX+estrogen re-placement group):
Animals in this group were trained, OVX was done and AD was induced as in group III. One week after LPS injection, animals were treated with estrogen supplementation (Estradiol 0.1mg/kg i.p.) daily for 1week, Group V: (AD+OVX+estrogen and progesterone replacement group): Animals in this group were trained, OVX was done and AD was induced as in group III. One week after LPS injection, animals were treated with estrogen supplementation (Estradiol 0. 1 mg/kg i.p.) and proges-terone supplementation (10mg/kg i.p.) once daily for 1 week.
At the end of experimental protocol of 6 weeks, the following parameters were assessed: behavioral assessment, determination of TNF-a (ER-a) level in serum, estimation of estrogen receptor-a, Bcl-2 and Seladin-1gene expression in brain tissue and estimation of the levels of MDA in brain tissue as well as histological and morphometric studies.
The results of the present study demonstrated that AD induced by single i.p. LPS injection produced significant increase in the square root transformed % of time in T-maze test and significant decrease in square root transformed % of activity in activity cage test and in square root transformed % of duration of rotations in seconds in rotarod test. This was produced through significant increase in serum TNF-a, significant decrease in Seladin-1and anti-apoptotic Bcl-2 gene expression in brain tissue, significant increase in MDA level in brain tissue, significant decrease in ER-a in brain tissue, increase in area % of dark nuclei and increase in area of amyloid plaques in brain tissue.
Ovariectomy induced a deterioration in the disease pa-rameters. Estrogen replacement in OVX rats provided partial reversal of impaired cognitive function, the increase in serum TNF-a, the decrease in Seladin-1 and Bcl-2 gene expression in brain tissue, and partial reversal of the increase in MDA level in brain tissue, the increase in area % of dark nuclei and the increase in area of plaques either alone or in combination with progesterone. Estrogen replacement resulted in complete reversal motor dysfunction either alone or in combination with progesterone, ER-a gene expression and area % of immunoexpression. It is to be noted that combination of estrogen with progesterone significantly increased Bcl-2 gene expression in brain tissue and significantly reduced the area of plaques as compared to estrogen alone.
Conclusion:
It can be concluded from the current study that LPS-induced AD produced deterioration of cognitive and motor functions. This deterioration was further aggravated by OVX. Estrogen replacement resulted in partial improvement in cognitive function and complete reversal of the motor dys-function partly through anti-inflammatory, anti-oxidant, anti-apoptotic and anti Aß effects mediated partly through ER-a. This protective effect of estrogen was potentiated by co-administration of progesterone.