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. 2023 Jul 6;24(8):e56525. doi: 10.15252/embr.202256525

Figure 8. SQSTM1/p62 expression in MNs increases with age.

Figure 8

  1. The search for genes differentially expressed in WT and En1‐Het mDA neurons and expressed in MNs, thus putative non‐cell‐autonomous EN1 targets in MNs, allowed for the identification of 402 genes (after pathway selection). These genes were investigated for an interaction with genes mutated in the main 4 familial ALS forms. Among them, p62/SQSTM1 (p62) expression is upregulated in the SNpc (RNA‐seq) and in MNs of En1‐Het mice.
  2. Immunohistochemical staining shows the presence of high amounts of p62/SQSTM1 in ChAT+ cell bodies of 3‐month‐old mice. Scale bar: 50 μm.
  3. Intensity measurements demonstrate that the mean of p62/SQSTM1 expression increases with age in WT γMNs (left) and αMNs (right). However, comparing WT and En1‐Het shows a significant difference only at 3 months and not later. Unpaired two‐sided t‐test. (*P < 0.05; **P < 0.005; ***P < 0.0005, ****P < 0.0001). Data information: This experiment was done once. Values are mean ± SD. Between 151 and 1,215 neurons and 3–5 mice were analyzed for each condition.
  4. Mean intensity of p62/SQSTM1 expression is increased in γMNs (left) and αMNs (right) in mice expressing scFvEN1 6 months after virus injection (7‐month‐old mice) demonstrating that EN1 extracellular neutralization increases p62/SQSTM1 expression. Expression of the mutated antibody (scFvMUT) does not increase p62/SQSTM1 expression. Unpaired two‐sided t‐test. (*P < 0.05; **P < 0.005; ***P < 0.0005, ****P < 0.0001).

Data information: This experiment was performed once. Values are mean ± SD. Between 448 and 759 neurons and 5 mice were analyzed for each condition.

Source data are available online for this figure.