Neurotransmitter receptors in mouse models of Alzheimer’s disease
Neurotransmitter receptors in mouse models of Alzheimer’s disease
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DissertationDate of Exam
15.05.2014Date of Publication
20.06.2014Advisor
Zilles, KarlCo-Referee
von der Emde, GerhardMetadata
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Abstract
Alzheimer's disease (AD) is the most common form of dementia. The disease occurs in a common sporadic and a familiar form (FAD). Both forms show a very similar clinical and pathological picture, with ß-amyloid (Aß) plaques being one of the main hallmarks. The aim of the study was to analyze the distribution and density of neurotransmitter receptors of the glutamatergic, cholinergic, GABAergic, serotonergic, adrenergic, dopaminergic and adenosinergic system in four mouse models of AD. Two of them, tgArcAβ and tg5xFAD mice, mirror mutations found in FAD, while one model, LRP1 mice, reflects a risk factor found in sporadic AD. The fourth model combines both factors (tg5xFAD/LRP1). Using quantitative receptor autoradiography, eight brain regions were investigated. Presence of Aβ was tested by the use of immunohistochemistry.
In all models, the glutamatergic, cholinergic, GABAergic and adrenergic system was affected. The cholinergic and GABAergic system revealed reduced receptor density, while the adrenergic receptors were increased in several regions. This indicates a similar mechanism in AD regarding these receptor systems. The glutamatergic kainate and mGlu2/3 receptors were reduced in all mouse models, with exception of increased kainate receptor density in tg5xFAD/LRP1 mice. NMDA receptor density was increased in tgArcAβ and LRP1 mice, while it was partly reduced in tg5xFAD and tg5xFAD/LRP1 mice, pointing to different alterations in the course of AD. The serotonergic receptors revealed differences in the tgArcAβ and tg5xFAD/LRP1 mice compared to controls, whereas the dopaminergic system was significantly affected only in the tg5xFAD mice. Accumulation of Aβ was observed in tg5xFAD, tg5xFAD/LRP1 and tgArcAβ mice in the cortex and hippocampus.
In summary, comparison of the alterations in the receptor density revealed similar changes in all models, although the mechanism behind the plaque generation is different in FAD and sporadic AD. Especially the density of glutamate, acetylcholine and noradrenaline receptors was strongly altered compared to control animals. Changes occurred well before plaque generation. Furthermore, the adrenergic receptor α2 was identified as a possible new therapeutic target.
In all models, the glutamatergic, cholinergic, GABAergic and adrenergic system was affected. The cholinergic and GABAergic system revealed reduced receptor density, while the adrenergic receptors were increased in several regions. This indicates a similar mechanism in AD regarding these receptor systems. The glutamatergic kainate and mGlu2/3 receptors were reduced in all mouse models, with exception of increased kainate receptor density in tg5xFAD/LRP1 mice. NMDA receptor density was increased in tgArcAβ and LRP1 mice, while it was partly reduced in tg5xFAD and tg5xFAD/LRP1 mice, pointing to different alterations in the course of AD. The serotonergic receptors revealed differences in the tgArcAβ and tg5xFAD/LRP1 mice compared to controls, whereas the dopaminergic system was significantly affected only in the tg5xFAD mice. Accumulation of Aβ was observed in tg5xFAD, tg5xFAD/LRP1 and tgArcAβ mice in the cortex and hippocampus.
In summary, comparison of the alterations in the receptor density revealed similar changes in all models, although the mechanism behind the plaque generation is different in FAD and sporadic AD. Especially the density of glutamate, acetylcholine and noradrenaline receptors was strongly altered compared to control animals. Changes occurred well before plaque generation. Furthermore, the adrenergic receptor α2 was identified as a possible new therapeutic target.
Subjects
Alzheimer, Neurotransmitter-Rezeptoren, Plaques, LRP1, ß-Amyloid, Alzheimer's disease, neurotransmitter receptors
Classification (DDC)
530 Physik 610 Medizin, Gesundheitvon Staden, Elena: Neurotransmitter receptors in mouse models of Alzheimer’s disease. - Bonn, 2014. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5n-36329
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5n-36329
@phdthesis{handle:20.500.11811/6101,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5n-36329,
author = {{Elena von Staden}},
title = {Neurotransmitter receptors in mouse models of Alzheimer’s disease},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2014,
month = jun,
note = {Alzheimer's disease (AD) is the most common form of dementia. The disease occurs in a common sporadic and a familiar form (FAD). Both forms show a very similar clinical and pathological picture, with ß-amyloid (Aß) plaques being one of the main hallmarks. The aim of the study was to analyze the distribution and density of neurotransmitter receptors of the glutamatergic, cholinergic, GABAergic, serotonergic, adrenergic, dopaminergic and adenosinergic system in four mouse models of AD. Two of them, tgArcAβ and tg5xFAD mice, mirror mutations found in FAD, while one model, LRP1 mice, reflects a risk factor found in sporadic AD. The fourth model combines both factors (tg5xFAD/LRP1). Using quantitative receptor autoradiography, eight brain regions were investigated. Presence of Aβ was tested by the use of immunohistochemistry.
In all models, the glutamatergic, cholinergic, GABAergic and adrenergic system was affected. The cholinergic and GABAergic system revealed reduced receptor density, while the adrenergic receptors were increased in several regions. This indicates a similar mechanism in AD regarding these receptor systems. The glutamatergic kainate and mGlu2/3 receptors were reduced in all mouse models, with exception of increased kainate receptor density in tg5xFAD/LRP1 mice. NMDA receptor density was increased in tgArcAβ and LRP1 mice, while it was partly reduced in tg5xFAD and tg5xFAD/LRP1 mice, pointing to different alterations in the course of AD. The serotonergic receptors revealed differences in the tgArcAβ and tg5xFAD/LRP1 mice compared to controls, whereas the dopaminergic system was significantly affected only in the tg5xFAD mice. Accumulation of Aβ was observed in tg5xFAD, tg5xFAD/LRP1 and tgArcAβ mice in the cortex and hippocampus.
In summary, comparison of the alterations in the receptor density revealed similar changes in all models, although the mechanism behind the plaque generation is different in FAD and sporadic AD. Especially the density of glutamate, acetylcholine and noradrenaline receptors was strongly altered compared to control animals. Changes occurred well before plaque generation. Furthermore, the adrenergic receptor α2 was identified as a possible new therapeutic target.},
url = {https://hdl.handle.net/20.500.11811/6101}
}
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5n-36329,
author = {{Elena von Staden}},
title = {Neurotransmitter receptors in mouse models of Alzheimer’s disease},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2014,
month = jun,
note = {Alzheimer's disease (AD) is the most common form of dementia. The disease occurs in a common sporadic and a familiar form (FAD). Both forms show a very similar clinical and pathological picture, with ß-amyloid (Aß) plaques being one of the main hallmarks. The aim of the study was to analyze the distribution and density of neurotransmitter receptors of the glutamatergic, cholinergic, GABAergic, serotonergic, adrenergic, dopaminergic and adenosinergic system in four mouse models of AD. Two of them, tgArcAβ and tg5xFAD mice, mirror mutations found in FAD, while one model, LRP1 mice, reflects a risk factor found in sporadic AD. The fourth model combines both factors (tg5xFAD/LRP1). Using quantitative receptor autoradiography, eight brain regions were investigated. Presence of Aβ was tested by the use of immunohistochemistry.
In all models, the glutamatergic, cholinergic, GABAergic and adrenergic system was affected. The cholinergic and GABAergic system revealed reduced receptor density, while the adrenergic receptors were increased in several regions. This indicates a similar mechanism in AD regarding these receptor systems. The glutamatergic kainate and mGlu2/3 receptors were reduced in all mouse models, with exception of increased kainate receptor density in tg5xFAD/LRP1 mice. NMDA receptor density was increased in tgArcAβ and LRP1 mice, while it was partly reduced in tg5xFAD and tg5xFAD/LRP1 mice, pointing to different alterations in the course of AD. The serotonergic receptors revealed differences in the tgArcAβ and tg5xFAD/LRP1 mice compared to controls, whereas the dopaminergic system was significantly affected only in the tg5xFAD mice. Accumulation of Aβ was observed in tg5xFAD, tg5xFAD/LRP1 and tgArcAβ mice in the cortex and hippocampus.
In summary, comparison of the alterations in the receptor density revealed similar changes in all models, although the mechanism behind the plaque generation is different in FAD and sporadic AD. Especially the density of glutamate, acetylcholine and noradrenaline receptors was strongly altered compared to control animals. Changes occurred well before plaque generation. Furthermore, the adrenergic receptor α2 was identified as a possible new therapeutic target.},
url = {https://hdl.handle.net/20.500.11811/6101}
}
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