estradiol-3-benzoate and Memory-Disorders

Estrogen deficiency is associated with cognitive impairment. Hormone replacement therapy (HRT) has proven to be effective in preventing and reversing the memory and learning deficiencies. However, conventional estrogenic treatment could increase the risks of breast cancer and venous thromboembolism. Tenuigenin (TEN) is putatively believed as the active component extracted from a Chinese herb Polygala tenuifolia root. Although TEN has been shown to enhance learning and memory in healthy mice, it remains unknown whether or not TEN could ameliorate learning and memory impairments. In the present study, mice were divided into four groups: sham-operated (sham), ovariectomized (OVX), OVX+estradiol benzoate (EB) and OVX+TEN groups. Step-through passive avoidance and Y-maze tests were used to assess learning and memory abilities, and the number of nitric oxide synthase (NOS) positive neurons and the synaptic measurement of hippocampal CA1 area were examined. The results showed that TEN was given orally to OVX mice, leading to the improvement of learning and memory in step-through passive avoidance and Y-maze tests. TEN could reduce the loss of NOS positive neurons and prevent the synaptic morphological changes induced by ovariectomy. Our results suggest that TEN may exert a potential therapeutic value for menopause cognitive dysfunction.

Topics: Animals; Avoidance Learning; CA1 Region, Hippocampal; Cognition Disorders; Drugs, Chinese Herbal; Estradiol; Female; Learning Disabilities; Maze Learning; Memory Disorders; Mice; NADPH Dehydrogenase; Ovariectomy; Psychomotor Performance; Synapses

Many toxic environmental and food agents have been suspected to be potential risk factors in inducing memory disabilities under normal and pathological conditions. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (known as dioxin or TCDD) is a common and prototypical member of a class of noxious environmental and food contaminants called the halogenated aromatic hydrocarbons. Since the role of dioxin in memory processes has not been studied in detail, the present report aims at elucidating the role of this pollutant in the maintenance of cognitive function. We found that TCDD (50miccrog/kg) induced spatial memory deficits in the Morris water maze (MWM) task in female but not male mice. This sex-dependant effect of dioxin seems to be related to the alteration of estrogen pathways, as treatment with 17beta-estradiol-3-benzoate (E; 5microg/day) reversed memory deficits induced by TCDD. We also observed that cognitive impairments produced by dioxin, which is known to interfere with retinoid turnover and metabolism, were abolished by retinoic acid (RA) treatment (150microg/kg). The cognitive effects of E and RA treatments seem to derive from common rather than additive mechanisms since memory deficits produced by TCDD were fully reversed by these compounds when used separately or in combination. Attenuation of dioxin-induced memory deficits in mice lacking transthyretin (TTR) suggests that TCDD may be acting by affecting the major route of retinol transport involving TTR. Taken together, these results suggest that the environmental and food pollutant TCDD can induce memory deficits by altering the estrogen pathways and a main route of TTR-mediated retinol transport.

Topics: Animals; Behavior, Animal; Biological Transport; Cognition; Environmental Pollutants; Estradiol; Estrogens; Female; Male; Memory; Memory Disorders; Mice; Mice, Inbred C57BL; Mice, Knockout; Polychlorinated Dibenzodioxins; Prealbumin; Sex Factors; Signal Transduction; Tretinoin; Vitamin A