Fig 2: ERK agonist attenuates the abundance of inclusions and restores the decrease of BDNF and DA in the mPFC. A SEW2871 upregulates the levels of phosphorylation of ERK and its downstream proteins. The Lewy body-like inclusions showed the opposite alterations. B Represent immunofluorescence images showing a significant increase in BDNF. Scale bars, 1mm (left) and 200 μm (right). G SEW2871 somewhat mitigates the decrease in DA content. C-F The corresponding statistical analyses. Bars represent the mean, error bars represent the SEM, and symbols represent biologically independent replicates (n). n = 3 in C-E. n = 5 in F. *P <0.05, **P <0.01.

Fig 3: PFF lead to decreased levels of BDNF in vivo and in vitro. A, G Represent immunofluorescence images of BDNF in the mPFC and primary neurons. Scale bars, 1 mm (left) and 200 μm (right) in A; 50 μm in G. C Representative blots showing a reduced BDNF level compared to PBS controls in the ipsilateral mPFC. E ELISA test of BDNF uncovers a similar change in primary mPFC neurons. B, D, F, H The corresponding statistical analyses. Bars represent the mean, error bars represent the SEM, and symbols represent biologically independent replicates (n). n = 3 in B and H; 5 in F. *P <0.05, **P <0.01.

Fig 4: PFF limits the internalization of TrkB at the cell membrane. A No significant change in the total TrkB in the mPFC. Scale bar, 1mm (left) and 200 μm (right). C TrkB leaves more on the cell membrane after exogenous BDNF stimulation. TrkB bands show membrane (upper) and total (lower) levels. E TrkB is disorganized in axons and more remains at the cell membrane after stimulation by exogenous BDNF. Scale bars, 50 μm. B, D, F The corresponding statistical analyses. Bars represent the mean, error bars represent the SEM, and symbols represent biologically independent replicates (n). n = 3 in B and F; 5 in D. **P <0.01, ***P <0.001, ns = no significant difference.