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Analyzing the influence of BDNF heterozygosity on spatial memory response to 17β-estradiol

The recent use of estrogen-based therapies as adjunctive treatments for the cognitive impairments of schizophrenia has produced promising results; however the mechanism behind estrogen-based cognitive enhancement is relatively unknown. Brain-derived neurotrophic factor (BDNF) regulates learning and...

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Autores principales: Wu, Y W C, Du, X, van den Buuse, M, Hill, R A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312832/
https://www.ncbi.nlm.nih.gov/pubmed/25603414
http://dx.doi.org/10.1038/tp.2014.143
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author Wu, Y W C
Du, X
van den Buuse, M
Hill, R A
author_facet Wu, Y W C
Du, X
van den Buuse, M
Hill, R A
author_sort Wu, Y W C
collection PubMed
description The recent use of estrogen-based therapies as adjunctive treatments for the cognitive impairments of schizophrenia has produced promising results; however the mechanism behind estrogen-based cognitive enhancement is relatively unknown. Brain-derived neurotrophic factor (BDNF) regulates learning and memory and its expression is highly responsive to estradiol. We recently found that estradiol modulates the expression of hippocampal parvalbumin-positive GABAergic interneurons, known to regulate neuronal synchrony and cognitive function. What is unknown is whether disruptions to the aforementioned estradiol–parvalbumin pathway alter learning and memory, and whether BDNF may mediate these events. Wild-type (WT) and BDNF heterozygous (+/−) mice were ovariectomized (OVX) at 5 weeks of age and simultaneously received empty, estradiol- or progesterone-filled implants for 7 weeks. At young adulthood, mice were tested for spatial and recognition memory in the Y-maze and novel-object recognition test, respectively. Hippocampal protein expression of BDNF and GABAergic interneuron markers, including parvalbumin, were assessed. WT OVX mice show impaired performance on Y-maze and novel-object recognition test. Estradiol replacement in OVX mice prevented the Y-maze impairment, a Behavioral abnormality of dorsal hippocampal origin. BDNF and parvalbumin protein expression in the dorsal hippocampus and parvalbumin-positive cell number in the dorsal CA1 were significantly reduced by OVX in WT mice, while E2 replacement prevented these deficits. In contrast, BDNF(+/−) mice showed either no response or an opposite response to hormone manipulation in both behavioral and molecular indices. Our data suggest that BDNF status is an important biomarker for predicting responsiveness to estrogenic compounds which have emerged as promising adjunctive therapeutics for schizophrenia patients.
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spelling pubmed-43128322015-02-09 Analyzing the influence of BDNF heterozygosity on spatial memory response to 17β-estradiol Wu, Y W C Du, X van den Buuse, M Hill, R A Transl Psychiatry Original Article The recent use of estrogen-based therapies as adjunctive treatments for the cognitive impairments of schizophrenia has produced promising results; however the mechanism behind estrogen-based cognitive enhancement is relatively unknown. Brain-derived neurotrophic factor (BDNF) regulates learning and memory and its expression is highly responsive to estradiol. We recently found that estradiol modulates the expression of hippocampal parvalbumin-positive GABAergic interneurons, known to regulate neuronal synchrony and cognitive function. What is unknown is whether disruptions to the aforementioned estradiol–parvalbumin pathway alter learning and memory, and whether BDNF may mediate these events. Wild-type (WT) and BDNF heterozygous (+/−) mice were ovariectomized (OVX) at 5 weeks of age and simultaneously received empty, estradiol- or progesterone-filled implants for 7 weeks. At young adulthood, mice were tested for spatial and recognition memory in the Y-maze and novel-object recognition test, respectively. Hippocampal protein expression of BDNF and GABAergic interneuron markers, including parvalbumin, were assessed. WT OVX mice show impaired performance on Y-maze and novel-object recognition test. Estradiol replacement in OVX mice prevented the Y-maze impairment, a Behavioral abnormality of dorsal hippocampal origin. BDNF and parvalbumin protein expression in the dorsal hippocampus and parvalbumin-positive cell number in the dorsal CA1 were significantly reduced by OVX in WT mice, while E2 replacement prevented these deficits. In contrast, BDNF(+/−) mice showed either no response or an opposite response to hormone manipulation in both behavioral and molecular indices. Our data suggest that BDNF status is an important biomarker for predicting responsiveness to estrogenic compounds which have emerged as promising adjunctive therapeutics for schizophrenia patients. Nature Publishing Group 2015-01 2015-01-20 /pmc/articles/PMC4312832/ /pubmed/25603414 http://dx.doi.org/10.1038/tp.2014.143 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Original Article
Wu, Y W C
Du, X
van den Buuse, M
Hill, R A
Analyzing the influence of BDNF heterozygosity on spatial memory response to 17β-estradiol
title Analyzing the influence of BDNF heterozygosity on spatial memory response to 17β-estradiol
title_full Analyzing the influence of BDNF heterozygosity on spatial memory response to 17β-estradiol
title_fullStr Analyzing the influence of BDNF heterozygosity on spatial memory response to 17β-estradiol
title_full_unstemmed Analyzing the influence of BDNF heterozygosity on spatial memory response to 17β-estradiol
title_short Analyzing the influence of BDNF heterozygosity on spatial memory response to 17β-estradiol
title_sort analyzing the influence of bdnf heterozygosity on spatial memory response to 17β-estradiol
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312832/
https://www.ncbi.nlm.nih.gov/pubmed/25603414
http://dx.doi.org/10.1038/tp.2014.143
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