Cargando…
Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice
Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease. We utilized apoE4‐targeted replacement mice (approved by the Tel Aviv University Animal Care Committee) to investigate whether cholinergic dysfunction, which increases during aging and is a hallmark of...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738402/ https://www.ncbi.nlm.nih.gov/pubmed/26526158 http://dx.doi.org/10.1111/jnc.13417 |
_version_ | 1782413604961648640 |
---|---|
author | Dolejší, Eva Liraz, Ori Rudajev, Vladimír Zimčík, Pavel Doležal, Vladimír Michaelson, Daniel M. |
author_facet | Dolejší, Eva Liraz, Ori Rudajev, Vladimír Zimčík, Pavel Doležal, Vladimír Michaelson, Daniel M. |
author_sort | Dolejší, Eva |
collection | PubMed |
description | Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease. We utilized apoE4‐targeted replacement mice (approved by the Tel Aviv University Animal Care Committee) to investigate whether cholinergic dysfunction, which increases during aging and is a hallmark of Alzheimer's disease, is accentuated by apoE4. This revealed that levels of the pre‐synaptic cholinergic marker, vesicular acetylcholine transporter in the hippocampus and the corresponding electrically evoked release of acetylcholine, are similar in 4‐month‐old apoE4 and apolipoprotein E3 (apoE3) mice. Both parameters decrease with age. This decrease is, however, significantly more pronounced in the apoE4 mice. The levels of cholinacetyltransferase (ChAT), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) were similar in the hippocampus of young apoE4 and apoE3 mice and decreased during aging. For ChAT, this decrease was similar in the apoE4 and apoE3 mice, whereas it was more pronounced in the apoE4 mice, regarding their corresponding AChE and BuChE levels. The level of muscarinic receptors was higher in the apoE4 than in the apoE3 mice at 4 months and increased to similar levels with age. However, the relative representation of the M1 receptor subtype decreased during aging in apoE4 mice. These results demonstrate impairment of the evoked release of acetylcholine in hippocampus by apoE4 in 12‐month‐old mice but not in 4‐month‐old mice. The levels of ChAT and the extent of the M2 receptor‐mediated autoregulation of ACh release were similar in the adult mice, suggesting that the apoE4‐related inhibition of hippocampal ACh release in these mice is not driven by these parameters. [Image: see text] Evoked ACh release from hippocampal and cortical slices is similar in 4‐month‐old apoE4 and apoE3 mice but is specifically and significantly reduced in hippocampus, but not cortex, of 12‐month‐old apoE4 mice. This effect is accompanied by decreased VAChT levels. These findings show that the hipocampal cholinergic nerve terminals are specifically affected by apoE4 and that this effect is age dependent. |
format | Online Article Text |
id | pubmed-4738402 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-47384022016-02-12 Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice Dolejší, Eva Liraz, Ori Rudajev, Vladimír Zimčík, Pavel Doležal, Vladimír Michaelson, Daniel M. J Neurochem Short Communications Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease. We utilized apoE4‐targeted replacement mice (approved by the Tel Aviv University Animal Care Committee) to investigate whether cholinergic dysfunction, which increases during aging and is a hallmark of Alzheimer's disease, is accentuated by apoE4. This revealed that levels of the pre‐synaptic cholinergic marker, vesicular acetylcholine transporter in the hippocampus and the corresponding electrically evoked release of acetylcholine, are similar in 4‐month‐old apoE4 and apolipoprotein E3 (apoE3) mice. Both parameters decrease with age. This decrease is, however, significantly more pronounced in the apoE4 mice. The levels of cholinacetyltransferase (ChAT), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) were similar in the hippocampus of young apoE4 and apoE3 mice and decreased during aging. For ChAT, this decrease was similar in the apoE4 and apoE3 mice, whereas it was more pronounced in the apoE4 mice, regarding their corresponding AChE and BuChE levels. The level of muscarinic receptors was higher in the apoE4 than in the apoE3 mice at 4 months and increased to similar levels with age. However, the relative representation of the M1 receptor subtype decreased during aging in apoE4 mice. These results demonstrate impairment of the evoked release of acetylcholine in hippocampus by apoE4 in 12‐month‐old mice but not in 4‐month‐old mice. The levels of ChAT and the extent of the M2 receptor‐mediated autoregulation of ACh release were similar in the adult mice, suggesting that the apoE4‐related inhibition of hippocampal ACh release in these mice is not driven by these parameters. [Image: see text] Evoked ACh release from hippocampal and cortical slices is similar in 4‐month‐old apoE4 and apoE3 mice but is specifically and significantly reduced in hippocampus, but not cortex, of 12‐month‐old apoE4 mice. This effect is accompanied by decreased VAChT levels. These findings show that the hipocampal cholinergic nerve terminals are specifically affected by apoE4 and that this effect is age dependent. John Wiley and Sons Inc. 2015-11-19 2016-02 /pmc/articles/PMC4738402/ /pubmed/26526158 http://dx.doi.org/10.1111/jnc.13417 Text en © 2015 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Short Communications Dolejší, Eva Liraz, Ori Rudajev, Vladimír Zimčík, Pavel Doležal, Vladimír Michaelson, Daniel M. Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice |
title | Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice |
title_full | Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice |
title_fullStr | Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice |
title_full_unstemmed | Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice |
title_short | Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice |
title_sort | apolipoprotein e4 reduces evoked hippocampal acetylcholine release in adult mice |
topic | Short Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738402/ https://www.ncbi.nlm.nih.gov/pubmed/26526158 http://dx.doi.org/10.1111/jnc.13417 |
work_keys_str_mv | AT dolejsieva apolipoproteine4reducesevokedhippocampalacetylcholinereleaseinadultmice AT lirazori apolipoproteine4reducesevokedhippocampalacetylcholinereleaseinadultmice AT rudajevvladimir apolipoproteine4reducesevokedhippocampalacetylcholinereleaseinadultmice AT zimcikpavel apolipoproteine4reducesevokedhippocampalacetylcholinereleaseinadultmice AT dolezalvladimir apolipoproteine4reducesevokedhippocampalacetylcholinereleaseinadultmice AT michaelsondanielm apolipoproteine4reducesevokedhippocampalacetylcholinereleaseinadultmice |