Figure 2

Long-term changes induced by a prenatal infection include increased anti- amyloid precursor protein (APP)/Aβ immunoreactivity (IR) and somatodendritic accumulation of pTau IR. Representative images of immunoperoxidase staining using (A,B) anti-Aβ_1–40/42 antibody and (D,E,G,H) anti-phosphorylated Tau²⁰⁵ taken from the dorsal hippocampus of 15-month-old non-transgenic mice prenatally exposed to saline (NaCl) or polyriboinosinic-polyribocytidilic acid (PolyI:C). Quantitative analyses of the area covered by (C) anti-APP/Aβ IR or (F) anti-pTau IR in hilar mossy cells. Values are given as mean ± SEM, n = 6 per treatment. *P < 0.05; statistical significance based on Mann–Whitney U test. (D,E) Translocation of pTau IR from axonal to somatodendritic compartments in the dentate gyrus (DG) and hilus after prenatal infection. (G-H) Representative higher-magnification image of the dorsal DG, showing the typical axonal pTau IR in the inner molecular layer of the DG (axonal terminals of contralateral hilar mossy cells, upper arrow) and in the neuropil of the hilus (axonal collaterals of DG granule cells, lower arrow) in NaCI-exposed control subjects. Compared with controls, a pronounced increase in pTau IR in somatic compartments was evident in the PolyI:C-treated offspring, as indicated by the distinct labeling of DG granule cells and hilar mossy cells (red arrows). At the same time, IR in the axonal compartments of the two cell types was strongly reduced. (I) Schematic overview of the observed changes within CA1 and DG between treatment groups, emphasizing the change in subcellular distribution of pTau from axonal to somatodendritic compartments. The drawing on the left highlights the dendritic arborization of a DG granule cell in the outer molecular layer, and indicates the axonal collaterals in the hilus. On the right, the projection of the mossy cells to the inner molecular layer of the DG (commissural; that is, targeting the contralateral hemisphere) are shown. Abbreviations: a, axonal projection area; d, dendritic subfield; gcl, granule cell layer; iml, inner molecular layer; oml, outer molecular layer; s, somatic subfield; slm, stratum lacunosum moleculare. Scale bars: B = 500 μm, H = 50 μm.