Reduced Serotonin Transporter Levels and Inflammation in the Midbrain Raphe of 12 Month Old APPswe/PSEN1dE9 Mice
Although mood and sleep disturbances are nearly universal among patients with Alzheimer's disease (AD), brain structures involved in non-cognitive processing remain under characterized in terms of AD pathology. This study was designed to evaluate hallmarks of AD pathology in the brainstem of th...
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Published in | Current Alzheimer research Vol. 15; no. 5; p. 420 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United Arab Emirates
14.03.2018
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Abstract | Although mood and sleep disturbances are nearly universal among patients with Alzheimer's disease (AD), brain structures involved in non-cognitive processing remain under characterized in terms of AD pathology.
This study was designed to evaluate hallmarks of AD pathology in the brainstem of the APPswe/PS1dE9 mouse model of familial AD.
Fresh-frozen sections from female, 12 month old, transgenic and control B6C3 mice (n=6/genotype) were examined for amyloid burden and neurofibrillary alterations, by using 6E10 immunohistochemistry and the Gallyas silver stain, respectively. Serotonin transporter (SERT) densities in the dorsal and the median raphe were quantified by [3H]DASB autoradiography. SERT mRNA expression was measured by RT-PCR and visualized by in situ hybridization. Neuroinflammation was evaluated by immunohistochemical staining for microglia and astrocytes, and by measuring mRNA levels of the proinflammatory cytokines TNF-α, IL-1β and IL-6.
No amyloid- and tau-associated lesions were observed in the midbrain raphe of 12 month old APPswe/PS1dE9 mice. SERT binding levels were reduced in transgenic animals compared to age-matched controls, and SERT mRNA levels were decreased by at least 50% from control values. Intense microglial, but not astrocytic immunoreactivity was observed in APPswe/PS1dE9 vs. wild-type mice. Levels of TNF-α mRNA were two-fold higher than control and correlated positively with SERT mRNA expression levels in transgenic animals.
There was no amyloid accumulation and tau-associated pathology in the midbrain raphe of 12 month old APPswe/PS1dE9 mice. However, there was a local neuroinflammatory response with loss of serotonergic markers, which may partially account for some of the behavioral symptoms of AD. |
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AbstractList | Although mood and sleep disturbances are nearly universal among patients with Alzheimer's disease (AD), brain structures involved in non-cognitive processing remain under characterized in terms of AD pathology.
This study was designed to evaluate hallmarks of AD pathology in the brainstem of the APPswe/PS1dE9 mouse model of familial AD.
Fresh-frozen sections from female, 12 month old, transgenic and control B6C3 mice (n=6/genotype) were examined for amyloid burden and neurofibrillary alterations, by using 6E10 immunohistochemistry and the Gallyas silver stain, respectively. Serotonin transporter (SERT) densities in the dorsal and the median raphe were quantified by [3H]DASB autoradiography. SERT mRNA expression was measured by RT-PCR and visualized by in situ hybridization. Neuroinflammation was evaluated by immunohistochemical staining for microglia and astrocytes, and by measuring mRNA levels of the proinflammatory cytokines TNF-α, IL-1β and IL-6.
No amyloid- and tau-associated lesions were observed in the midbrain raphe of 12 month old APPswe/PS1dE9 mice. SERT binding levels were reduced in transgenic animals compared to age-matched controls, and SERT mRNA levels were decreased by at least 50% from control values. Intense microglial, but not astrocytic immunoreactivity was observed in APPswe/PS1dE9 vs. wild-type mice. Levels of TNF-α mRNA were two-fold higher than control and correlated positively with SERT mRNA expression levels in transgenic animals.
There was no amyloid accumulation and tau-associated pathology in the midbrain raphe of 12 month old APPswe/PS1dE9 mice. However, there was a local neuroinflammatory response with loss of serotonergic markers, which may partially account for some of the behavioral symptoms of AD. |
Author | Thygesen, Camilla Ilkjaer, Laura Finsen, Bente Darvesh, Sultan Vaitheeswaran, Ramanan Metaxas, Athanasios Jensen, Katrine T |
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Keywords | SERT neuroinflammation median raphe dorsal raphe brainstem Alzheimer's disease APPswe/PS1dE9 |
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SubjectTerms | Alzheimer Disease - metabolism Alzheimer Disease - pathology Amyloid beta-Protein Precursor - genetics Amyloid beta-Protein Precursor - metabolism Animals Astrocytes - metabolism Astrocytes - pathology Disease Models, Animal Female Humans Inflammation - metabolism Inflammation - pathology Mice, Inbred C3H Mice, Inbred C57BL Mice, Transgenic Microglia - metabolism Microglia - pathology Midbrain Raphe Nuclei - metabolism Midbrain Raphe Nuclei - pathology Presenilin-1 - genetics Presenilin-1 - metabolism RNA, Messenger - metabolism Serotonin Plasma Membrane Transport Proteins - metabolism Tumor Necrosis Factor-alpha - metabolism |
Title | Reduced Serotonin Transporter Levels and Inflammation in the Midbrain Raphe of 12 Month Old APPswe/PSEN1dE9 Mice |
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