TY  - JOUR
AU  - Martínez-Rojas, Beatriz
AU  - Martín-Pérez, Samuel
AU  - Giraldo, Esther
AU  - Lopez-Mocholi, Eric
AU  - Alastrue, Ana
AU  - Andrade-Talavera, Yuniesky
AU  - Prius-Mengual, Jose
AU  - Paniagua, Guillem
AU  - Pedraza, Maria
AU  - Hingorani, Sonia
AU  - Rost, Benjamin R
AU  - Schmitz, Dietmar
AU  - Llansola, Marta
AU  - Felipo, Vicente
AU  - Rodríguez-Moreno, Antonio
AU  - Moreno-Manzano, Victoria
TI  - Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-00768
SP  - 5885
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Female
KW  - Spinal Cord Injuries: physiopathology
KW  - Spinal Cord Injuries: metabolism
KW  - Spinal Cord Injuries: therapy
KW  - Cyclic AMP: metabolism
KW  - Pyramidal Tracts: metabolism
KW  - Pyramidal Tracts: physiopathology
KW  - Optogenetics: methods
KW  - Rats
KW  - Recovery of Function: physiology
KW  - Adenylyl Cyclases: metabolism
KW  - Adenylyl Cyclases: genetics
KW  - Neurons: metabolism
KW  - Neurons: physiology
KW  - Rats, Sprague-Dawley
KW  - Locomotion: physiology
KW  - Serotonergic Neurons: metabolism
KW  - Neuronal Plasticity
KW  - Cyclic AMP (NLM Chemicals)
KW  - Adenylyl Cyclases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40592902
C2  - pmc:PMC12216545
DO  - DOI:10.1038/s41467-025-61018-3
UR  - https://pub.dzne.de/record/279437
ER  -