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EARLY-LIFE STRESS AND TAMOXIFEN DISRUPT ESTROGEN AND NEUROTRANSMITTER RECEPTOR BALANCE IN THE HIPPOCAMPUS:
N Bukia1, M Butskhrikidze2, M Siradze3
11Iv.Beritashvili Center of Experimental Biomedicine, Tbilisi; 2Caucasus International University, Tbilisi, Georgia.
Background:
Early-life stress is a known risk factor for adult cognitive deficits, mediated in part by disruption of hippocampal estrogen receptors and neurotransmitter systems. Tamoxifen, as a selective estrogen receptor modulator, worsens cognitive function. Electromagnetic stimulation (EMS) helps improve this process.
Aim:
The aim of study was investigating the effects of early-life immobilization stress and tamoxifen on hippocampal ERα, ERβ, NMDA, AMPA, and GABA receptor expression in rats, and to evaluate whether EMS mitigates these effects.
Methods:
Newborn rats were divided into six groups (n = 7/group): control, control+EMS, immobilization, immobilization+EMS, tamoxifen, and tamoxifen+EMS. Chronic immobilization or tamoxifen was applied during postnatal days 1-20. EMS was applied during days 21-30. Receptor levels were quantified via appropriate biochemical assays on postnatal day 80.
Results:
Tamoxifen significantly suppressed ERα and ERβ expression, while stress mainly reduced ERβ. NMDA receptor levels were reduced by both tamoxifen and stress. AMPA receptors was increased by tamoxifen but normalized by EMS. GABA receptors expression increased in stressed and tamoxifen groups, and decreased with EMS. EMS significantly restored ERβ and partially normalized NMDA and GABA levels.
Conclusion:
Early-life stress, as well as tamoxifen, disrupt hippocampal receptor homeostasis, which may lead to cognitive decline in adulthood. EMS has the potential to normalize these neurochemical alterations. Research in this direction may contribute to the development of new therapeutic approaches aimed at preventing stress-induced impairments originating in early life.
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