Fig. 4: Attenuated Parkinsonian pathology by wtTIDM in PFF-seeded A53T mice. | Nature Communications

Fig. 4: Attenuated Parkinsonian pathology by wtTIDM in PFF-seeded A53T mice.

From: Selective targeting of the TLR2/MyD88/NF-κB pathway reduces α-synuclein spreading in vitro and in vivo

Fig. 4

Nigral pathology in α-syn PFF-injected A53T control and wtTIDM/mTIDM administered mice was evaluated by immunohistochemical staining of TH (a) followed by stereological counting of viable TH + ve neurons in SN (b, n = 5 animals, p = 0.00052 for A53T + PBS vs A53T + PFF and p = 0.0025 for A53T + PFF vs A53T + PFF + wtTIDM). Images are shown at ×5 magnification, scale bar is 200 µm. TH protein level in SN was monitored by immunoblotting (c) and relative TH expression with respect to actin is shown (d, n = 4 animals, p = 0.0226 for A53T + PBS vs A53T + PFF and p = 0.0171 for A53T + PFF vs A53T + PFF + wtTIDM). Striatal pathology in experimental groups was checked by immunostaining of TH neuronal fibers in striatum (e). TH optical intensity was measured by Fiji and relative TH fiber intensity as a percentage to the nTg control brain is presented (f, n = 5 animals, p = 0.0005 for A53T + PBS vs A53T + PFF and p = 0.00034 for A53T + PFF vs A53T + PFF + wtTIDM). Images are shown at ×4 magnification. TH protein level in striatum is shown by immunoblotting (g, h, n = 4 animals, p = 0.0193 for A53T + PBS vs A53T + PFF and p = 0.0337 for A53T + PFF vs A53T + PFF + wtTIDM). Level of dopamine (DA, n = 4 animals, p = 0.0211 for A53T + PBS vs A53T + PFF and p = 0.0411 for A53T + PFF vs A53T + PFF + wtTIDM), 3, 4-dihydroxyphenylacetic acid (DOPAC, n = 4), and homovanillic acid (HVA, n = 4) was measured by HPLC-ECD method and the amount of neurotransmitters per mg of tissue was calculated (i–k). Behavioral performance of animals is demonstrated by a number of rearing (l, n = 6 animals, p = 0.0011 for A53T + PBS vs A53T + PFF and p = 0.0107 for A53T + PFF vs A53T + PFF + wtTIDM) and latency to fall down in rotarod test (m, n = 6 animals, p = 0.00045 for A53T + PBS vs A53T + PFF and p = 0.0044 for A53T + PFF vs A53T + PFF + wtTIDM). One-way ANOVA followed by Tukey’s multiple comparison tests was conducted for statistical analyses. *p < 0.05, **p < 0.01, ***p < 0.001 indicate significance compared to respective groups. Values are given as mean ± SEM.

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