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@ARTICLE{MartnezRojas:279437,
      author       = {Martínez-Rojas, Beatriz and Martín-Pérez, Samuel and
                      Giraldo, Esther and Lopez-Mocholi, Eric and Alastrue, Ana
                      and Andrade-Talavera, Yuniesky and Prius-Mengual, Jose and
                      Paniagua, Guillem and Pedraza, Maria and Hingorani, Sonia
                      and Rost, Benjamin R and Schmitz, Dietmar and Llansola,
                      Marta and Felipo, Vicente and Rodríguez-Moreno, Antonio and
                      Moreno-Manzano, Victoria},
      title        = {{S}timulation of corticospinal neurons by optogenetic
                      c{AMP} inductions promotes motor recovery after spinal cord
                      injury in female rats via raphespinal tract modulation.},
      journal      = {Nature Communications},
      volume       = {16},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DZNE-2025-00768},
      pages        = {5885},
      year         = {2025},
      abstract     = {After spinal cord injury (SCI), cyclic adenosine
                      monophosphate (cAMP) levels drop in the spinal cord, cortex
                      and brainstem, unlike in regenerating peripheral neurons. To
                      address SCI recovery, we expressed photoactivatable
                      adenylate cyclase (bPAC) in corticospinal neurons of female
                      rats with dorsal hemisection for on-demand cAMP inductions.
                      bPAC stimulation restored passive and firing properties of
                      corticospinal neurons, promoted early and sustained
                      locomotor recovery and increased corticospinal tract
                      plasticity. Additionally, bPAC enhanced sparing of
                      lumbar-projecting brainstem neurons after SCI, accompanied
                      by activation of cAMP signaling in the raphe-reticular
                      formation and increased excitatory/inhibitory
                      neurotransmitter balance. Accordingly, augmented density of
                      serotonergic tracts was found caudal to the injury in bPAC
                      rats, correlating with enhanced functional performance.
                      Serotonergic implication in motor recovery was further
                      evidenced by selective depletion, resulting in the
                      abrogation of bPAC-mediated recovery. Overall, our findings
                      underscore that cAMP induction in corticospinal neurons
                      enhances locomotion after SCI, through a cortical rerouting
                      pathway via the serotonergic descending tract.},
      keywords     = {Animals / Female / Spinal Cord Injuries: physiopathology /
                      Spinal Cord Injuries: metabolism / Spinal Cord Injuries:
                      therapy / Cyclic AMP: metabolism / Pyramidal Tracts:
                      metabolism / Pyramidal Tracts: physiopathology /
                      Optogenetics: methods / Rats / Recovery of Function:
                      physiology / Adenylyl Cyclases: metabolism / Adenylyl
                      Cyclases: genetics / Neurons: metabolism / Neurons:
                      physiology / Rats, Sprague-Dawley / Locomotion: physiology /
                      Serotonergic Neurons: metabolism / Neuronal Plasticity /
                      Cyclic AMP (NLM Chemicals) / Adenylyl Cyclases (NLM
                      Chemicals)},
      cin          = {AG Schmitz},
      ddc          = {500},
      cid          = {I:(DE-2719)1810004},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40592902},
      pmc          = {pmc:PMC12216545},
      doi          = {10.1038/s41467-025-61018-3},
      url          = {https://pub.dzne.de/record/279437},
}