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Dissertation zugänglich unter
Ovarian steroids and their influence on hippocampal memory function and morphology
Ovarielle Steroide und ihr Einfluss auf hippocampale Gedächtnisfunktion und Morphologie.
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Hippocampus , Gedächtnis , Östrogene , Progesteron , Kernspintomographie
Freie Schlagwörter (Deutsch):
Freie Schlagwörter (Englisch):
Hippocampus , Memory , Estrogen , Progesterone , functional imaging
Pawlik, Kurt (Prof. Dr.)
Tag der mündlichen Prüfung:
Kurzfassung auf Englisch:
The ovarian steroids estradiol and progesterone play a critical role in the regulation of hippocampal plasticity. Estradiol has been shown to increase the growth of new spines and synapses and to facilitate hippocampal long-term potentiation. In line with findings on the cellular level, animal studies evidence beneficial effects of estradiol on hippocampus-dependent memory. Although much less investigated, progesterone can counteract several estradiol-related effects. Unfortunately, human studies about hormonal effects on the hippocampus and hippocampus-dependent memory are rare and highly equivocal. The present thesis aims to contribute data to the understanding of hormonal effects on the human hippocampus. For this purpose, four experiments were conducted assessing hippocampus-dependent memory performance as well as hippocampal structure and activity by means of magnetic-resonance tomography. Experiment 1 investigated the consequences of pharmacologically-induced decreases in estradiol synthesis. In this study, postmenopausal women suffering from hormone-sensitive breast cancer and age-matched controls were tested before onset of anti-hormone therapy and three to six months later. Behaviorally, anti-hormone therapy was associated with worse performance in a specific subdomain of hippocampus-dependent verbal memory. On the neuronal level, anti-hormone therapy increased neural responses in the anterior cingulate and the prefrontal cortex during a verbal source memory task. Results of Experiment 1 suggest that anti-hormone therapy impaired hippocampus-dependent verbal memory and increased prefrontal activity. Experiment 2 made use of a polymorphism associated to differences in estradiol serum levels in men. Hippocampal volume and hippocampus-dependent memory performance were examined across genotype groups within three independent cohorts, differing with respect to their genetic disposition to either high or low serum estradiol levels. Analysis of structural brain
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images showed, that the genotype group with a disposition to high estradiol levels had higher volumes of the posterior hippocampus within both hemispheres. In contrast, hippocampus-dependent memory did not differ significantly between genotype groups. These results show that a genetic disposition to higher E2 levels is associated with higher macroscopic hippocampal volume in men. Experiments 3 and 4 examined women during two phases of their menstrual cycle. In both experiments, women were tested once during the early follicular phase, when estrogen and progesterone levels are low, and once during the luteal phase, in which estradiol is at a medium peak and progesterone is at its maximum. In Experiment 3, functional neuroimaging was recorded during encoding of emotional and neutral pictures in both cycle phases. Retrieval was conducted two days after encoding outside the scanner. Behavioral analyses yielded a significant valence by cycle interaction for recollection-based memory, which was mainly driven by decreases in recollection-based memory for negative pictures in the high- relative to the low-hormone phase. On the neuronal level, the hippocampus as well as prefrontal areas showed significant variations in their neural responses across menstrual cycle phases. Behavioral results of Experiment 3 suggest that hormones decrease the efficacy of negatively valenced arousal to stimulate hippocampus-dependent consolidation. Experiment 4 examined variations in hippocampal structure across the menstrual cycle. In line with existing literature, hippocampal volumes were higher when estradiol and progesterone were both low, compared with a cycle phase in which estradiol and progesterone were both high. Findings of Experiment 4 highlight the critical role of progesterone in the regulation of macroscopic hippocampal volume. In summary, present results underscore the variety of hormonal effects on the human memory system and their sensitivity to experimental factors. Furthermore, current results suggest that at least a part of the inconsistency in human literature can be accounted by not differeniating between hippocampus-dependent and -independent memory functions.