Altered Affect, Monoamine Transmitters and Bioenergetic Homeostasis of Alpha-synuclein-transgenic Mice, in the Presence and Absence of Endogenous Alpha-synuclein
Parkinson’s disease can be caused by A53T or A30P mutations in the α-synuclein (SNCA) gene, or by multiplication of the gene locus. Patients often experience depression and anxiety. We investigated affect, serotonin content and bioenergetic homeostasis of mice expressing human wild-type (WT), A53T...
Main Author: | |
---|---|
Other Authors: | |
Language: | en_ca |
Published: |
2010
|
Subjects: | |
Online Access: | http://hdl.handle.net/1807/24552 |
id |
ndltd-TORONTO-oai-tspace.library.utoronto.ca-1807-24552 |
---|---|
record_format |
oai_dc |
spelling |
ndltd-TORONTO-oai-tspace.library.utoronto.ca-1807-245522014-02-21T03:56:50ZAltered Affect, Monoamine Transmitters and Bioenergetic Homeostasis of Alpha-synuclein-transgenic Mice, in the Presence and Absence of Endogenous Alpha-synucleinCumyn, Elizabeth M.Alpha-synucleinaffect0317Parkinson’s disease can be caused by A53T or A30P mutations in the α-synuclein (SNCA) gene, or by multiplication of the gene locus. Patients often experience depression and anxiety. We investigated affect, serotonin content and bioenergetic homeostasis of mice expressing human wild-type (WT), A53T, A30P or A53T+A30P (DM) SNCA transgenes. A30P-Tg mice displayed altered affect, increased serotonin turnover and reduced ATP and complex I+III activity. To determine whether murine α-synuclein (Snca) might mask effects SNCA transgenes we re-examined effects of SNCA transgenes in Snca-/- mice. SNCA transgenes rescued anxiety, serotonin levels and ATP content in Snca-/- mice. Only A53T SNCA abrogated behavioural despair associated with decreased norepinephrine in Snca-/- brains. The A53T residue is the natural sequence of murine Snca, and appears to be important for synuclein function in mice. The Snca-/- mouse provides a means to study the effects of SNCA mutants, and the physiologic roles of Snca in vivo.Mount, Howard2010-062010-07-22T18:00:51ZNO_RESTRICTION2010-07-22T18:00:51Z2010-07-22T18:00:51ZThesishttp://hdl.handle.net/1807/24552en_ca |
collection |
NDLTD |
language |
en_ca |
sources |
NDLTD |
topic |
Alpha-synuclein affect 0317 |
spellingShingle |
Alpha-synuclein affect 0317 Cumyn, Elizabeth M. Altered Affect, Monoamine Transmitters and Bioenergetic Homeostasis of Alpha-synuclein-transgenic Mice, in the Presence and Absence of Endogenous Alpha-synuclein |
description |
Parkinson’s disease can be caused by A53T or A30P mutations in the α-synuclein (SNCA) gene, or by multiplication of the gene locus. Patients often experience depression and anxiety. We investigated affect, serotonin content and bioenergetic homeostasis of mice expressing human wild-type (WT), A53T, A30P or A53T+A30P (DM) SNCA transgenes. A30P-Tg mice displayed altered affect, increased serotonin turnover and reduced ATP and complex I+III activity. To determine whether murine α-synuclein (Snca) might mask effects SNCA transgenes we re-examined effects of SNCA transgenes in Snca-/- mice. SNCA transgenes rescued anxiety, serotonin levels and ATP content in Snca-/- mice. Only A53T SNCA abrogated behavioural despair associated with decreased norepinephrine in Snca-/- brains. The A53T residue is the natural sequence of murine Snca, and appears to be important for synuclein function in mice. The Snca-/- mouse provides a means to study the effects of SNCA mutants, and the physiologic roles of Snca in vivo. |
author2 |
Mount, Howard |
author_facet |
Mount, Howard Cumyn, Elizabeth M. |
author |
Cumyn, Elizabeth M. |
author_sort |
Cumyn, Elizabeth M. |
title |
Altered Affect, Monoamine Transmitters and Bioenergetic Homeostasis of Alpha-synuclein-transgenic Mice, in the Presence and Absence of Endogenous Alpha-synuclein |
title_short |
Altered Affect, Monoamine Transmitters and Bioenergetic Homeostasis of Alpha-synuclein-transgenic Mice, in the Presence and Absence of Endogenous Alpha-synuclein |
title_full |
Altered Affect, Monoamine Transmitters and Bioenergetic Homeostasis of Alpha-synuclein-transgenic Mice, in the Presence and Absence of Endogenous Alpha-synuclein |
title_fullStr |
Altered Affect, Monoamine Transmitters and Bioenergetic Homeostasis of Alpha-synuclein-transgenic Mice, in the Presence and Absence of Endogenous Alpha-synuclein |
title_full_unstemmed |
Altered Affect, Monoamine Transmitters and Bioenergetic Homeostasis of Alpha-synuclein-transgenic Mice, in the Presence and Absence of Endogenous Alpha-synuclein |
title_sort |
altered affect, monoamine transmitters and bioenergetic homeostasis of alpha-synuclein-transgenic mice, in the presence and absence of endogenous alpha-synuclein |
publishDate |
2010 |
url |
http://hdl.handle.net/1807/24552 |
work_keys_str_mv |
AT cumynelizabethm alteredaffectmonoaminetransmittersandbioenergetichomeostasisofalphasynucleintransgenicmiceinthepresenceandabsenceofendogenousalphasynuclein |
_version_ |
1716648056007426048 |