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Reduced Serotonin Transporter Levels and Inflammation in the Midbrain Raphe of 12 Month Old APPswe/PSEN1dE9 Mice
- Source :
- Metaxas, A, Vaitheeswaran, R, Jensen, K T, Thygesen, C, Ilkjaer, L, Darvesh, S & Finsen, B 2018, ' Reduced Serotonin Transporter Levels and Inflammation in the Midbrain Raphe of 12 month old APPswe/PSEN1dE9 Mice ', Current Alzheimer Research, vol. 15, no. 5, pp. 420-428 . https://doi.org/10.2174/1567205014666171004113537
- Publication Year :
- 2018
- Publisher :
- Bentham Science Publishers Ltd., 2018.
-
Abstract
- Background: 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. Objectives: This study was designed to evaluate hallmarks of AD pathology in the brainstem of the APPswe/PS1dE9 mouse model of familial AD. Methods: 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. Results: 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. Conclusions: 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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Mice, Transgenic
In situ hybridization
DASB
Serotonergic
Midbrain Raphe Nuclei
Amyloid beta-Protein Precursor
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Dorsal raphe nucleus
Neuroinflammation
Alzheimer Disease
Internal medicine
Presenilin-1
medicine
Animals
Humans
RNA, Messenger
Serotonin transporter
Inflammation
Serotonin Plasma Membrane Transport Proteins
Mice, Inbred C3H
Raphe
biology
Tumor Necrosis Factor-alpha
business.industry
SERT
APP /PS1
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Endocrinology
Neurology
chemistry
Astrocytes
biology.protein
Female
Microglia
Neurology (clinical)
business
Alzheimer’s disease
Brainstem
Median raphe
Dorsal raphe
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15672050
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Current Alzheimer Research
- Accession number :
- edsair.doi.dedup.....f7a743e9cd173bf5eafcd066628eebd5