Abstract | BACKGROUND: METHODS: RESULTS: At 8 months of age there was no difference in LC tyrosine hydroxylase (TH) across all groups and cortical NA levels of TASTPM/ DSP-4, WT/Vehicle and WT/ DSP-4 were similar. NA levels were lowest in TASTPM/Vehicle. Messenger ribonucleic acid ( mRNA) for various inflammatory markers were significantly increased in TASTPM/Vehicle compared with WT/Vehicle and by 8 months of age DSP-4 treatment modified this by reducing the levels of some of these markers in TASTPM. TASTPM/Vehicle showed increased astrocytosis and a significantly larger area of cortical amyloid plaque compared with TASTPM/ DSP-4. However, by 11 months, NA levels were lowest in TASTPM/ DSP-4 and there was a significant reduction in LC TH of TASTPM/ DSP-4 only. Both TASTPM groups had comparable levels of amyloid, microglial activation and astrocytosis and mRNA for inflammatory markers was similar except for interleukin-1 beta which was increased by DSP-4. TASTPM mice were cognitively impaired at 8 and 11 months but DSP-4 did not modify this. CONCLUSION: These data reveal that a low dose of DSP-4 can have varied effects on the modulation of amyloid plaque deposition and neuroinflammation in TASTPM mice dependent on the duration of dosing.
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Authors | Perdita L Pugh, Martin P Vidgeon-Hart, Tracey Ashmeade, Ainsley A Culbert, Zoe Seymour, Marion J Perren, Flora Joyce, Simon T Bate, Anna Babin, David J Virley, Jill C Richardson, Neil Upton, David Sunter |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 4
Pg. 8
(Feb 26 2007)
ISSN: 1742-2094 [Electronic] England |
PMID | 17324270
(Publication Type: Journal Article)
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Chemical References |
- Amyloid beta-Protein Precursor
- Benzylamines
- Presenilin-1
- DSP 4
- Norepinephrine
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Topics |
- Amyloid beta-Protein Precursor
(antagonists & inhibitors, genetics, metabolism)
- Animals
- Benzylamines
(administration & dosage, toxicity)
- Corpus Striatum
(drug effects, metabolism)
- Drug Administration Schedule
- Humans
- Inflammation
(genetics, metabolism, prevention & control)
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Mutation
- Norepinephrine
(antagonists & inhibitors, biosynthesis, genetics)
- Plaque, Amyloid
(drug effects, genetics, metabolism)
- Presenilin-1
(antagonists & inhibitors, genetics, metabolism)
- Transgenes
(drug effects)
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