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Autoanticuerpos anti-CASPR2 inducen hiperactividad neuronal en organoides cerebrales humanos
Ana Rafaela Oliveira1,2,3, Giuseppe Cammarata1,4, Catarina Seabra1,3
1CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Journal of neurochemistry
|February 23, 2026
Resumen
Los autoanticuerpos maternos dirigidos contra la proteína 2 asociada a contactina (CASPR2) pueden alterar el desarrollo cerebral fetal. La exposición a anticuerpos anti-CASPR2 en organoides neuronales humanos indujo hiperexcitabilidad neuronal, un sello distintivo de los trastornos del neurodesarrollo.
Área de la Ciencia:
- Neurociencia; Biología del Desarrollo; Inmunología
Sus antecedentes:
- La transferencia gestacional de anticuerpos reactivos contra el cerebro plantea riesgos para los trastornos del neurodesarrollo.
- La proteína 2 asociada a contactina (CASPR2) es un objetivo de los autoanticuerpos maternos implicados en el neurodesarrollo fetal.
- El impacto preciso de los anticuerpos anti-CASPR2 en el desarrollo del cerebro humano no se comprende bien.
Objetivo del estudio:
- Investigar los efectos neurofisiológicos de los autoanticuerpos anti-CASPR2 en el desarrollo del cerebro humano.
- Elucidar los mecanismos subyacentes a las alteraciones del neurodesarrollo inducidas por anticuerpos anti-CASPR2.
Principales métodos:
- Se cultivaron organoides neuronales humanos no guiados durante 6 meses en medios con anticuerpos anti-CASPR2.
- Se realizó la caracterización neurofisiológica mediante patch-clamp de célula completa y obtención de imágenes de calcio en cortes agudos de organoides.
Principales resultados:
- La exposición a anticuerpos anti-CASPR2 aumentó significativamente la actividad sináptica espontánea.
- Se observaron mejoras en la frecuencia máxima de disparo de potenciales de acción y en la actividad espontánea de la red.
- Las alteraciones en la forma del potencial de acción sugieren el papel de CASPR2 en la regulación de los canales de potasio dependientes de voltaje.
Conclusiones:
- Los autoanticuerpos anti-CASPR2 inducen hiperexcitabilidad neuronal en organoides cerebrales humanos.
- Este fenotipo de hiperexcitabilidad refleja los hallazgos en modelos de trastornos del neurodesarrollo.
- Los autoanticuerpos anti-CASPR2 pueden desempeñar un papel patológico en la inducción de hiperexcitabilidad neuronal durante el desarrollo.
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