Is it possible to improve memory function by upregulation of the cholesterol 24S-hydroxylase (CYP46A1) in the brain?
We previously described a heterozygous mouse model overexpressing human HA-tagged 24S-hydroxylase (CYP46A1) utilizing a ubiquitous expression vector. In this study, we generated homozygotes of these mice with circulating levels of 24OH 30-60% higher than the heterozygotes. Female homozygous CYP46A1...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3712995?pdf=render |
| _version_ | 1811262708026179584 |
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| author | Silvia Maioli Ann Båvner Zeina Ali Maura Heverin Muhammad-Al-Mustafa Ismail Elena Puerta Maria Olin Ahmed Saeed Marjan Shafaati Paolo Parini Angel Cedazo-Minguez Ingemar Björkhem Ingemar Björkhem |
| author_facet | Silvia Maioli Ann Båvner Zeina Ali Maura Heverin Muhammad-Al-Mustafa Ismail Elena Puerta Maria Olin Ahmed Saeed Marjan Shafaati Paolo Parini Angel Cedazo-Minguez Ingemar Björkhem Ingemar Björkhem |
| author_sort | Silvia Maioli |
| collection | DOAJ |
| description | We previously described a heterozygous mouse model overexpressing human HA-tagged 24S-hydroxylase (CYP46A1) utilizing a ubiquitous expression vector. In this study, we generated homozygotes of these mice with circulating levels of 24OH 30-60% higher than the heterozygotes. Female homozygous CYP46A1 transgenic mice, aged 15 months, showed an improvement in spatial memory in the Morris water maze test as compared to the wild type mice. The levels of N-Methyl-D-Aspartate receptor 1, phosphorylated-N-Methyl-D-Aspartate receptor 2A, postsynaptic density 95, synapsin-1 and synapthophysin were significantly increased in the hippocampus of the CYP46A1 transgenic mice as compared to the controls. The levels of lanosterol in the brain of the CYP46A1 transgenic mice were significantly increased, consistent with a higher synthesis of cholesterol. Our results are discussed in relation to the hypothesis that the flux in the mevalonate pathway in the brain is of importance in cognitive functions. |
| first_indexed | 2024-04-12T19:31:42Z |
| format | Article |
| id | doaj.art-2ff61c800796445390811baa10e7bf25 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T19:31:42Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2ff61c800796445390811baa10e7bf252022-12-22T03:19:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6853410.1371/journal.pone.0068534Is it possible to improve memory function by upregulation of the cholesterol 24S-hydroxylase (CYP46A1) in the brain?Silvia MaioliAnn BåvnerZeina AliMaura HeverinMuhammad-Al-Mustafa IsmailElena PuertaMaria OlinAhmed SaeedMarjan ShafaatiPaolo PariniAngel Cedazo-MinguezIngemar BjörkhemIngemar BjörkhemWe previously described a heterozygous mouse model overexpressing human HA-tagged 24S-hydroxylase (CYP46A1) utilizing a ubiquitous expression vector. In this study, we generated homozygotes of these mice with circulating levels of 24OH 30-60% higher than the heterozygotes. Female homozygous CYP46A1 transgenic mice, aged 15 months, showed an improvement in spatial memory in the Morris water maze test as compared to the wild type mice. The levels of N-Methyl-D-Aspartate receptor 1, phosphorylated-N-Methyl-D-Aspartate receptor 2A, postsynaptic density 95, synapsin-1 and synapthophysin were significantly increased in the hippocampus of the CYP46A1 transgenic mice as compared to the controls. The levels of lanosterol in the brain of the CYP46A1 transgenic mice were significantly increased, consistent with a higher synthesis of cholesterol. Our results are discussed in relation to the hypothesis that the flux in the mevalonate pathway in the brain is of importance in cognitive functions.http://europepmc.org/articles/PMC3712995?pdf=render |
| spellingShingle | Silvia Maioli Ann Båvner Zeina Ali Maura Heverin Muhammad-Al-Mustafa Ismail Elena Puerta Maria Olin Ahmed Saeed Marjan Shafaati Paolo Parini Angel Cedazo-Minguez Ingemar Björkhem Ingemar Björkhem Is it possible to improve memory function by upregulation of the cholesterol 24S-hydroxylase (CYP46A1) in the brain? PLoS ONE |
| title | Is it possible to improve memory function by upregulation of the cholesterol 24S-hydroxylase (CYP46A1) in the brain? |
| title_full | Is it possible to improve memory function by upregulation of the cholesterol 24S-hydroxylase (CYP46A1) in the brain? |
| title_fullStr | Is it possible to improve memory function by upregulation of the cholesterol 24S-hydroxylase (CYP46A1) in the brain? |
| title_full_unstemmed | Is it possible to improve memory function by upregulation of the cholesterol 24S-hydroxylase (CYP46A1) in the brain? |
| title_short | Is it possible to improve memory function by upregulation of the cholesterol 24S-hydroxylase (CYP46A1) in the brain? |
| title_sort | is it possible to improve memory function by upregulation of the cholesterol 24s hydroxylase cyp46a1 in the brain |
| url | http://europepmc.org/articles/PMC3712995?pdf=render |
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