Alterations in the human brain in menopause.
In a series of studies we showed that menopause in women causes alterations not only in the neuronal expression of estrogen receptors (ER) alpha and beta, but also in local estrogen production in several brain areas and in the rate of neuronal metabolism. Although such changes are clearly brain region-specific, there seems to be no evidence at present for a decrease in neuronal metabolic rate. On the contrary, an increase in the neuronal metabolic activity and in the level of ERalpha in postmenopausal women was noted. In the supraoptic nucleus (SON) that is a major source of plasma arginine-vasopressin (AVP) we found that neuronal metabolic activity as judged from the Golgi apparatus and cell size was markedly enhanced in women after menopause accompanied by an increase in ERalpha and a decrease in ERbeta. Similar changes were noted in the medial mamillary nucleus and in the hippocampus that are involved in the regulation of learning and memory. Recently we aimed at determining whether in addition to the canonical ERalpha and ERbeta, estrogen receptor splice variants lacking entire exons may also be involved in the menopause-associated changes in the human brain. We detected del. 2 (missing exon 2), del. 4 (lacking exon 4), del. 7 (exon 7 absent) and MB1 (deletion of 168 nucleotides in the exon 1) in the frozen hippocampal tissue of 6 women (46, 52, 59, 64, 77 and 83 years of age). No age-related changes were observed for the mentioned splice forms in women of this group.
Ishunina
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TA
Netherlands Institute for Neuroscience, Amsterdam, The Netherlands. T.Ishunina@nin.knaw.nl
Swaab
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DF
D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism; D005091:Exons; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D006984:Hypertrophy; D007031:Hypothalamus / Q000502:physiology*; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009154:Mutation; D047648:Perimenopause / Q000502:physiology*; D017698:Postmenopause / Q000502:physiology*; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020800:Receptor, Nerve Growth Factor