Translational control of nociception via 4E-binding protein 1

  1. Arkady Khoutorsky
  2. Robert P Bonin
  3. Robert E Sorge
  4. Christos G Gkogkas
  5. Sophie Anne Pawlowski
  6. Seyed Mehdi Jafarnejad
  7. Mark H Pitcher
  8. Tommy Alain
  9. Jimena Perez-Sanchez
  10. Eric W Salter
  11. Loren Martin
  12. Alfredo Ribeiro-da-Silva
  13. Yves De Koninck
  14. Fernando Cervero
  15. Jeffrey S Mogil  Is a corresponding author
  16. Nahum Sonenberg  Is a corresponding author
  1. McGill University, Canada
  2. Institut universitaire en santé mentale de Québec, Canada
  3. University of Edinburgh, United Kingdom
  4. National Center for Complementary and Alternative Medicine, National Institutes of Health, Porter Neuroscience Research Center, United States
  5. Université Laval, Canada
7 figures

Figures

Figure 1 with 3 supplements
Eif4ebp1-/- mice exhibit mechanical hypersensitivity and increased formalin response.

Mechanical pain sensitivity is increased in Eif4ebp1-/- mice as evident by decreased von Frey thresholds (A, n=8/genotype) and shortened latencies to attack tail clip (A, n=8/genotype), whereas …

https://doi.org/10.7554/eLife.12002.003
Figure 1—figure supplement 1
Eif4ebp1/2 DKO mice, but not Eif4ebp2-/-, mice exhibit mechanical hypersensitivity and enhanced formalin responding.

Mechanical and thermal pain sensitivities are not altered in Eif4ebp2-/- mice as evident by data from von Frey and tail clip assays (A, n=9/genotype), and radiant heat paw-withdrawal and hot-plate …

https://doi.org/10.7554/eLife.12002.004
Figure 1—figure supplement 2
No gross alterations in the dorsal horn of the Eif4ebp1-/- mice.

To assess the possibility of spinal cord reorganization in Eif4ebp1-/- mice, we performed immunostaining of NeuN (A), Substance P (SP, B), calcitonin gene-related peptide (CGRP, C), isolectin B4 …

https://doi.org/10.7554/eLife.12002.005
Figure 1—figure supplement 3
Distribution of lentivirus-driven eGFP expression.

Lentiviruses expressing eGFP were microinjected (intraparenchymal injection (IPI)) directly into the dorsal horn of the lumbar spinal cord. Seven days later the spinal cord was extracted and …

https://doi.org/10.7554/eLife.12002.006
Increased levels of eIF4F complex in Eif4ebp1-/- mice cause mechanical hypersensitivity and increased formalin response.

(A) Left, Immunoblot analysis of cap column pull-down proteins prepared from the spinal cord of Eif4ebp1-/- and wild-type mice (WT) treated with 4EGI-1 (10 μg, i.t. once a day for 3 days) or …

https://doi.org/10.7554/eLife.12002.007
Excitatory and inhibitory synaptic transmissions are increased in the spinal cord of Eif4ebp1-/- mice.

Representative traces (top) of mEPSCs (A) and mIPSCs (B) from lamina II neurons in acute lumbar spinal cord slices from Eif4ebp1-/- and wild-type mice (WT). Bar graphs (bottom) show mEPSC (A) and …

https://doi.org/10.7554/eLife.12002.008
Enhanced expression of neuroligin 1 contributes to mechanical hypersensitivity of Eif4ebp1-/- mice.

(A) General translation is not altered in Eif4ebp1-/- mice as assessed by puromycin incorporation (n=3/genotype). (B) Protein expression of neuroligin (NLGN) 1, 2 and 3 is increased in synaptosomes …

https://doi.org/10.7554/eLife.12002.009
Figure 5 with 1 supplement
Reduction of neuroligin 1 levels in Eif4ebp1-/- mice normalizes the enhanced excitatory synaptic transmission. mEPSCs

(A) and mIPSCs (B) were recorded from lamina II spinal neurons of wild-type (WT), Eif4ebp1-/-, Eif4ebp1-/-/Nlgn1+/- and Nlgn1+/- mice. Top: representative traces of recordings from the four …

https://doi.org/10.7554/eLife.12002.010
Figure 5—figure supplement 1
Input resistance and membrane capacitance are not altered in lamina II spinal neurons from Eif4ebp1-/-, Eif4ebp1-/-/Nlgn1+/- and Nlgn1+/- mice.

Input resistance (A) and membrane capacitance (B) of lamina II spinal neurons from wild-type (WT) (n=11), Eif4ebp1-/- (n=9), Eif4ebp1-/-/Nlgn1+/- (n=10) and Nlgn1+/- mice (n=7). No differences were …

https://doi.org/10.7554/eLife.12002.011

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