Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.778203
Title: Estrogens regulate the synaptic proteome in a sexually dimorphic manner through local protein synthesis
Author: Raval, Pooja
ISNI:       0000 0004 7963 9391
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2019
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Abstract:
Estrogens, particularly its biologically active form 17β-estradiol (estradiol), have repeatedly been illustrated to have long-lasting influences over cognitive function and behaviour, which is believed to be, in part, driven by estrogenic regulation of synaptic plasticity. Specifically, estrogens have been shown to rapidly, within minutes, regulate dendritic spine dynamics, and shape synapse structure and function. Critically, the rapid effects of estrogens on synapses are mediated by specific signalling pathways, which have been shown to be required for estrogenic-facilitation of learning and memory. More recently, emerging evidence indicates that estrogens regulate learning and memory through the modulation of local protein synthesis; the ability to produce nascent proteins without the need for gene transcription. However, the molecular and cellular mechanisms that underlie estrogen's ability to regulate local protein synthesis and furthermore, whether such a mechanism can ultimately impact synaptic function in both male and female brains is currently unknown. The role of acute estrogen signalling in regulating local protein synthesis within the hippocampus of males and females was investigated in this thesis. Employing a combination of Surface Sensing of Translation (SUnSET) and fluorescent non-canonical amino acid tagging (FUNCAT) assays, estradiol was found to increase protein synthesis within 2 hour estradiol treatment in male and ovariectomised (OVX) hippocampal slices. This was mediated by two different signalling pathways in both sexes. Interestingly, in concert with this increased local translation, there was an increase in a subset of synaptic proteins and dendritic spines observed within the same time-frame in both sexes. These proteins are targeted to dendritic spines in the primary neuronal model. This study proposes a novel mode of estrogen signaling that could result in long-lasting changes in neuronal circuitry and cognitive function. Further research is warranted to test the beneficial effects of estradiol in the context of a local protein synthesis mechanism being therapeutic.
Supervisor: Srivastava, Deepak Prakash ; Vance, Caroline Anne Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.778203  DOI: Not available
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