Short-term ABX reduces Aβ-associated degenerative changes in male mice, and FMT reverts these changes in ABX-treated male mice.
(A) Representative low (a–e) and high (f–o) magnification images of 3D6+ plaque (green)-localized, NF-L (red) from M_Ctr (a, f, and k), M_Abx (b, g, and l), M_Abx+FMT (c, h, and m), F_Ctr (d, i, and n), and F_Abx (e, j, and o) mice. Note the arrows in k and m indicate swollen neurites in M_Ctr and M_Abx+FMT, while asterisk in l represents lack of swollen neurites in M_Abx. Arrowheads in n and o represent swollen dystrophic neurites in F_Ctr and F_Abx mice. (B) Representative low (a–e) and high (f–o) magnification images of LAMP1 immunolabeled (red) dystrophic axons in close proximity to 3D6+ plaque (green) from M_Ctr (a, f, and k), M_Abx (b, g, and l), M_Abx+FMT (c, h, and m), F_Ctr (d, i, and n), and F_Abx (e, j, and o) mice. Note the arrows in b indicate lower levels of Aβ (green) plaques and associated LAMP1 reactivity (red) in M_Abx compared with M_Ctr (a). Majority of LAMP1 reactivity was observed around the plaques, and Iba1+ microglia (purple) cells did not colocalize with LAMP1 (red). (C) Representative low (a–e) and high (f–o) magnification of 3D6+ plaque-localized synaptophysin (a presynaptic terminal marker: red) from M_Ctr (a, f, and k), M_Abx (b, g, and l), M_Abx+FMT (c, h, and m), F_Ctr (d, i, and n), and F_Abx (e, j, and o) mice. Note the arrows in k and m indicate swollen dystrophic presynaptic terminals and lack of synaptophysin boutons in close proximity to Aβ plaques in M_Ctr and M_Abx+FMT. Arrowheads in n and o represent swollen dystrophic presynaptic terminals in F_Ctr and F_Abx mice. (D) Representative low (a–e) and high (f–o) magnification of 3D6+ plaque-localized PSD95 (a postsynaptic terminal marker: red) from M_Ctr (a, f, and k), M_Abx (b, g, and l), M_Abx+FMT (c, h, and m), F_Ctr (d, i, and n), and F_Abx (e, j, and o) mice. Note the arrows in k and m indicate the absence of PSD95 immunoreactive postsynaptic terminals in close proximity to Aβ plaques in M_Ctr and M_Abx+FMT. Arrowheads in n and o represent the absence of PSD95 immunoreactive postsynaptic terminals in close proximity to Aβ plaques in F_Ctr and F_Abx mice. M_Ctr = vehicle-treated male, M_Abx = ABX-treated (PND14–PND21) male, M_Abx+FMT = ABX-treated (PND14–PND21) male, followed by FMT (PND24–PND63) from age-matched Tg-donor male, F_Ctr = vehicle-treated female, and F_Abx = ABX-treated (PND14–PND21) female. Scale bars in A, e, B, e, C, e, and D, e represent 200 µm and apply to all panels in A, a–e, B, a–e, C, a–e, and D, a–e. Scale bars in A, j, A, o, B, j, B, o, C, j, C, o, D, j, and D, o represent 15 µm and apply to all panels in A, f–o, B, f–o, C, f–o, and D, f–o.