Does genetic testing for ERα gene polymorphisms provide new possibilities of treatment for cognitive function disorders in postmenopausal women?

Abstract

It is commonly considered that cognitive abilities decrease with age, especially with respect to processing and psychomotor speed. It is an interesting issue whether, apart from the ageing process, the undergoing of menopause itself deteriorates cognitive functions, compared to women at reproductive age. Hopes for improvement of cognitive functions were pinned on the use of menopausal hormone therapy. However, the results of studies concerning the effect of hormone replacement therapy on cognition proved to be contradictory. It seems that the essence of the problem is more complicated than only estrogen deficiency. It is suggested that estrogen receptor α (ERα) polymorphism may be responsible for the differences in the effect of estrogens on cognitive processes. The article presents current knowledge concerning the effect of estrogens on the central nervous system, especially the role of ERα polymorphism, with respect to foreseeing benefits from the use of exogenous estrogens for cognitive functions. At the present stage of research, ERα appears to be poorly specific; nevertheless, it may be an important instrument for the classification of peri- and post-menopausal patients in the group where therapy with the use of estrogens may bring about benefits in terms of prevention and treatment of cognitive disorders. It also seems necessary to conduct prophylactic, screening examination of cognitive functions in post-menopausal women, in order to identify those at risk of the development of dementia.

Saikosaponin‑D improves fear memory deficits in ovariectomized rats via the action of estrogen receptor‑α in the hippocampus

“…Conversely, significant alterations in erα expression were detected in the hippocampus of oVX rats following SSd treatment. erα has frequently been reported to be associated with spine structure and/or postsynaptic functions (47,48); for example, selective activation of erα in oVX mice results in an increased spine density in the hippocampus, which is inversely correlated with memory dysfunction (49). in particular, ici182780, a non-selective inhibitor of ers, markedly blocked the memory improvement induced by SSd in oVX rats, thus corroborating a mechanism of SSd-mediated memory restoration via ers.…”

Effect of interactions between APOE and ESR1 polymorphisms on cognitive functions in postmenopausal women

“…Two polymorphisms within ESR1 (rs9340799 – 351A>G ( Xba I) and rs2234693 – 397T>C ( Pvu II), separated by only 46 base pairs) are noted to play a role in several diseases [ 6 – 8 ]. It is also suggested that both ESR1 polymorphisms may have an impact on cognitive functioning [ 9 , 10 ]. However, there are also contrary results in the topic [ 11 ].…”

Oestrogen receptor α gene polymorphisms, insomnia, and cognitive functions in perimenopausal and postmenopausal women in non-manual employment

“…One of the candidate genes that may be responsible for the problems considered is the oestrogen receptor a gene ( ESR1 ). In the central nervous system (CNS), ESR1 occurs in the hypothalamus, olfactory lobe, amygdale, and hippocampus; therefore, in the regions related with memory, mood, and the rhythm of sleep and wakefulness [ 23 ].…”