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Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy

View Article: PubMed Central - PubMed

ABSTRACT

The role of immune responses in the cognitive impairments associated with tauopathy is unclear. Laurent et al. identify a CD8+ T-cell infiltration in the hippocampus of THY-Tau22 transgenic mice. T-cell depletion reverses spatial memory deficits in these animals, supporting a role for hippocampal T-cell infiltration in tau-driven cognitive impairments.

No MeSH data available.


Glial cell activation in the hippocampus of THY-Tau22 mice. (A and B) As seen using an antibody revealing pSer422 immunoreactivity, THY-Tau22 mice exhibit a high level of abnormally phosphorylated tau species in the CA1 region of hippocampus at 12 months of age. (C and D) CD11b immunostaining point out progressive microglial (C, arrows) and astroglial (D) reponses in the hippocampal CA1 area of THY-Tau22 mice (bottom) as compared to wild-type (WT) animals (top). n = 3/group. Scale bars = 500 µm (B); 100 µm (C and D).
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aww270-F1: Glial cell activation in the hippocampus of THY-Tau22 mice. (A and B) As seen using an antibody revealing pSer422 immunoreactivity, THY-Tau22 mice exhibit a high level of abnormally phosphorylated tau species in the CA1 region of hippocampus at 12 months of age. (C and D) CD11b immunostaining point out progressive microglial (C, arrows) and astroglial (D) reponses in the hippocampal CA1 area of THY-Tau22 mice (bottom) as compared to wild-type (WT) animals (top). n = 3/group. Scale bars = 500 µm (B); 100 µm (C and D).

Mentions: We first evaluated glial cell activation in the hippocampus of THY-Tau22 mice, from an early stage (3 months of age), i.e. when hippocampal tau pathology starts developing, to later stages (12 months of age), when pathology and memory deficits are maximal in this mouse model (Burnouf et al., 2012; Van der Jeugd et al., 2013). As expected from previous studies in several tau transgenic models (Yoshiyama et al., 2007; Bellucci et al., 2011; Laurent et al., 2014), immunostainings for CD11b and GFAP showed significant microgliosis and astrocytosis, which were spatiotemporally correlated with hippocampal tau pathology in THY-Tau22 mice, as compared to wild-type littermates (Fig. 1). Accordingly, we found significant mRNA upregulation of innate immunity markers such as Tlr2 (toll-like receptor 2), Cd68 and Tnfa (tumor necrosis factor α) (Supplementary Fig. 1).Figure 1


Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy
Glial cell activation in the hippocampus of THY-Tau22 mice. (A and B) As seen using an antibody revealing pSer422 immunoreactivity, THY-Tau22 mice exhibit a high level of abnormally phosphorylated tau species in the CA1 region of hippocampus at 12 months of age. (C and D) CD11b immunostaining point out progressive microglial (C, arrows) and astroglial (D) reponses in the hippocampal CA1 area of THY-Tau22 mice (bottom) as compared to wild-type (WT) animals (top). n = 3/group. Scale bars = 500 µm (B); 100 µm (C and D).
© Copyright Policy - cc-by-nc
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5382942&req=5

aww270-F1: Glial cell activation in the hippocampus of THY-Tau22 mice. (A and B) As seen using an antibody revealing pSer422 immunoreactivity, THY-Tau22 mice exhibit a high level of abnormally phosphorylated tau species in the CA1 region of hippocampus at 12 months of age. (C and D) CD11b immunostaining point out progressive microglial (C, arrows) and astroglial (D) reponses in the hippocampal CA1 area of THY-Tau22 mice (bottom) as compared to wild-type (WT) animals (top). n = 3/group. Scale bars = 500 µm (B); 100 µm (C and D).
Mentions: We first evaluated glial cell activation in the hippocampus of THY-Tau22 mice, from an early stage (3 months of age), i.e. when hippocampal tau pathology starts developing, to later stages (12 months of age), when pathology and memory deficits are maximal in this mouse model (Burnouf et al., 2012; Van der Jeugd et al., 2013). As expected from previous studies in several tau transgenic models (Yoshiyama et al., 2007; Bellucci et al., 2011; Laurent et al., 2014), immunostainings for CD11b and GFAP showed significant microgliosis and astrocytosis, which were spatiotemporally correlated with hippocampal tau pathology in THY-Tau22 mice, as compared to wild-type littermates (Fig. 1). Accordingly, we found significant mRNA upregulation of innate immunity markers such as Tlr2 (toll-like receptor 2), Cd68 and Tnfa (tumor necrosis factor α) (Supplementary Fig. 1).Figure 1

View Article: PubMed Central - PubMed

ABSTRACT

The role of immune responses in the cognitive impairments associated with tauopathy is unclear. Laurent et al. identify a CD8+ T-cell infiltration in the hippocampus of THY-Tau22 transgenic mice. T-cell depletion reverses spatial memory deficits in these animals, supporting a role for hippocampal T-cell infiltration in tau-driven cognitive impairments.

No MeSH data available.