Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation

[EN] 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 dor...

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Detalhes bibliográficos
Autores: Martinez-Rojas, Beatriz, Martín-Pérez, Samuel, López Mocholi, Eric, Alastrue, Ana, Andrade-Talavera, Yuniesky, Prius-Mengual, Jose, Paniagua Soriano, Guillem, Pedraza, María, Hingorani, Sonia, Rost, Benjamin R., Schmitz, Dietmar, Llansola, Marta, Felipo, Vicente, Rodríguez-Moreno, Antonio, Moreno-Manzano, Victoria, Giraldo, Esther|||0000-0001-5488-3011
Tipo de documento: artigo
Data de publicação:2025
País:España
Recursos:Universitat Politècnica de València (UPV)
Repositório:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglês
OAI Identifier:oai:dnet:riunet______::fcd1fb165ca5f2986635f8d19d94f998
Acesso em linha:https://riunet.upv.es/handle/10251/235804
Access Level:Acceso aberto
Palavra-chave:Spinal Cord Injury (SCI)
CAMP inductions
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Descrição
Resumo:[EN] 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, aug mented density of serotonergic tracts was found caudal to the injury in bPAC rats, correlating with enhanced functional performance. Serotonergic implica tion 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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