Tph2 Genetic Ablation Contributes to Senile Plaque Load and Astrogliosis in APP/PS1 Mice

Author(s): Chao-Jin Xu, Jun-Ling Wang, Jing-Pan, Min-Liao*

Journal Name: Current Alzheimer Research

Volume 16 , Issue 3 , 2019

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Background: Amyloid-β (Aβ) accumulation plays a critical role in the pathogenesis of Alzheimer’s disease (AD) lesions. Deficiency of Serotonin signaling recently has been linked to the increased Aβ level in transgenic mice and humans. In addition, tryptophan hydroxylase-2 (Tph2), a second tryptophan hydroxylase isoform, controls brain serotonin synthesis. However, it remains to be determined that whether Tph2 deficient APP/PS1mice affect the formation of Aβ plaques in vivo.

Methods: Both quantitative and qualitative immunochemistry methods, as well as Congo red staining were used to evaluate the Aβ load and astrogliosis in these animals.

Results: we studied alterations of cortex and hippocampus in astrocytes and senile plaques by Tph2 conditional knockout (Tph2 CKO) AD mice from 6-10 months of age. Using Congo red staining and immunostained with Aβ antibody, we showed that plaques load or plaques numbers significantly increased in Tph2 CKO experimental groups at 8 to 10 months old, compared to wild type (WT) group, respectively. Using GFAP+ astrocytes immunofluorescence method, we found that the density of GFAP+ astrocytes markedly enhanced in Tph2 CKO at 10 months. We showed Aβ plaques co-localized autophagic markers LC3 and p62. Nevertheless, we did not observe any co-localization between GFAP+ astrocytes and autophagic markers, but detected the co-localization between βIII-tubulin+ neurons and autophagic markers.

Conclusion: Overall, our work provides the preliminary evidence in vivo that Tph2 plays a role in amyloid plaques generation.

Keywords: Tph2, Aβ plaque, APP/PS1, autophagy, astrocyte, Alzheimer's disease.

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Year: 2019
Page: [219 - 232]
Pages: 14
DOI: 10.2174/1567205016666190301110110
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