Endocrine Abstracts

The incidence of Alzheimer’s disease (AD) is higher in women than men. Our study aimed to investigate the behavioral, biochemical, and histological changes in lipopolysaccharide (LPS)-induced AD, to study effect of estrogen in AD clarifying the possible involved underlying mechanisms and its modulation by progestsserone.

Groups: Female albino rats were divided into control, AD, AD+ovariectomy (OVX), AD+OVX+estrogen replacement and AD+OVX+estrogen+progesterone replacement groups. Levels of activity using the activity cage, motor coordination using the rotarod, cognitive abilities using T-maze, serum TNFα, estrogen receptor α, Bcl-2 and Seladin-1 gene expression, MDA levels in brain tissue, histological and morphometric studies were estimated.

Results: Increased time in T-maze, decreased activity in activity cage, duration of rotations in rotarod, increased TNFα, decreased Seladin-1and Bcl-2 expression, increased MDA level, decreased ERα, increased area percent of dark nuclei and area of amyloid plaques in AD group. Increased time in T-maze, decreased duration of rotations in rotarod, non-significantly changed activity in activity cage, increased TNFα, decreased Seladin-1 expression, ERα expression and area percent of ER immunoexpression, Bcl-2 expression, increased area percent of dark nuclei, MDA level and area of amyloid plaques in AD+OVX group was shown. Estrogen decreased time in T-maze, increased activity in activity cage, duration of rotations in rotarod, decreased TNFα, increased Seladin-1, Bcl-2, and ERα expression and area percent of immunoexpression, decreased MDA level, area percent of dark nuclei and area of plaques either alone or in combination with progesterone.

Conclusion: LPS-induced AD produced deterioration of cognitive and motor functions which was further aggravated by OVX. Estrogen improved the cognitive and motor dysfunction partly through anti-inflammatory, anti-oxidant, anti-apoptotic and anti Aβ effects mediated partly through ER-α which was potentiated by co-administration of progesterone.