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000279437 1001_ $$00000-0001-7513-1396$$aMartínez-Rojas, Beatriz$$b0
000279437 245__ $$aStimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.
000279437 260__ $$a[London]$$bSpringer Nature$$c2025
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000279437 520__ $$aAfter 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.
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000279437 650_7 $$0E0399OZS9N$$2NLM Chemicals$$aCyclic AMP
000279437 650_7 $$0EC 4.6.1.1$$2NLM Chemicals$$aAdenylyl Cyclases
000279437 650_2 $$2MeSH$$aAnimals
000279437 650_2 $$2MeSH$$aFemale
000279437 650_2 $$2MeSH$$aSpinal Cord Injuries: physiopathology
000279437 650_2 $$2MeSH$$aSpinal Cord Injuries: metabolism
000279437 650_2 $$2MeSH$$aSpinal Cord Injuries: therapy
000279437 650_2 $$2MeSH$$aCyclic AMP: metabolism
000279437 650_2 $$2MeSH$$aPyramidal Tracts: metabolism
000279437 650_2 $$2MeSH$$aPyramidal Tracts: physiopathology
000279437 650_2 $$2MeSH$$aOptogenetics: methods
000279437 650_2 $$2MeSH$$aRats
000279437 650_2 $$2MeSH$$aRecovery of Function: physiology
000279437 650_2 $$2MeSH$$aAdenylyl Cyclases: metabolism
000279437 650_2 $$2MeSH$$aAdenylyl Cyclases: genetics
000279437 650_2 $$2MeSH$$aNeurons: metabolism
000279437 650_2 $$2MeSH$$aNeurons: physiology
000279437 650_2 $$2MeSH$$aRats, Sprague-Dawley
000279437 650_2 $$2MeSH$$aLocomotion: physiology
000279437 650_2 $$2MeSH$$aSerotonergic Neurons: metabolism
000279437 650_2 $$2MeSH$$aNeuronal Plasticity
000279437 7001_ $$00009-0007-7062-8695$$aMartín-Pérez, Samuel$$b1
000279437 7001_ $$00000-0001-5488-3011$$aGiraldo, Esther$$b2
000279437 7001_ $$00000-0001-8206-9869$$aLopez-Mocholi, Eric$$b3
000279437 7001_ $$aAlastrue, Ana$$b4
000279437 7001_ $$00000-0002-5295-0169$$aAndrade-Talavera, Yuniesky$$b5
000279437 7001_ $$aPrius-Mengual, Jose$$b6
000279437 7001_ $$00000-0003-2292-5330$$aPaniagua, Guillem$$b7
000279437 7001_ $$aPedraza, Maria$$b8
000279437 7001_ $$aHingorani, Sonia$$b9
000279437 7001_ $$0P:(DE-2719)2810914$$aRost, Benjamin R$$b10
000279437 7001_ $$0P:(DE-2719)2810725$$aSchmitz, Dietmar$$b11$$udzne
000279437 7001_ $$00000-0002-5565-5907$$aLlansola, Marta$$b12
000279437 7001_ $$00000-0003-3145-9538$$aFelipo, Vicente$$b13
000279437 7001_ $$00000-0002-8078-6175$$aRodríguez-Moreno, Antonio$$b14
000279437 7001_ $$00000-0002-6035-9491$$aMoreno-Manzano, Victoria$$b15
000279437 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-61018-3$$gVol. 16, no. 1, p. 5885$$n1$$p5885$$tNature Communications$$v16$$x2041-1723$$y2025
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