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Ciencia básica y patogénesis

Titikorn Chunchai1,2, Hiranya Pintana1,2, Patcharapong Pantiya1,2

  • 1Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 23, 2025
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La dieta crónica alta en grasas y el LPS inducen un comportamiento similar a la depresión al alterar la neurogénesis. Los inhibidores de P2X7 y la minociclina restauraron la neurogénesis y atenuaron los comportamientos depresivos en ratas obesas, lo que sugiere un potencial terapéutico.

Palabras clave:
dieta alta en grasasLPSdepresiónneurogénesisinhibidores de P2X7obesidadminociclinaratascomportamiento depresivoinflamación

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Área de la Ciencia:

  • Neurociencia
  • Inmunología
  • Metabolismo

Sus antecedentes:

  • La dieta crónica alta en grasas (HFD) y la administración de lipopolisacáridos (LPS) promueven la neuroinflamación y los comportamientos similares a la depresión.
  • La activación de la microglía a través del receptor de purinérgicos P2X7 está implicada en la inflamación inducida por LPS y la producción de ATP.
  • El impacto de los inhibidores de P2X7 en la neurogénesis y el comportamiento en la obesidad inducida por la dieta bajo desafío inmunitario no se comprende bien.

Objetivo del estudio:

  • Investigar los efectos de la inhibición de P2X7 sobre el peso corporal, la grasa visceral, el peso del bazo, la neurogénesis y el comportamiento similar a la depresión.
  • Evaluar el potencial terapéutico de los inhibidores de P2X7 en ratas obesas desafiadas con LPS.

Principales métodos:

  • Las ratas Wistar fueron alimentadas con una dieta normal (ND) o HFD durante 12 semanas.
  • Las ratas recibieron solución salina, minociclina o un inhibidor de P2X7 (JNJ-55308942) antes de la inyección de LPS.
  • El comportamiento similar a la depresión se evaluó utilizando la prueba de nado forzado y la neurogénesis se evaluó en el giro dentado.

Principales resultados:

  • La dieta alta en grasas (HFD) aumentó el peso corporal y la grasa visceral. Tanto la minociclina como el inhibidor de P2X7 redujeron el peso del bazo en ratas alimentadas con HFD, lo que indica efectos antiinflamatorios.
  • La neurogénesis, evaluada por células positivas a SOX2, se redujo en ratas alimentadas con HFD pero se restauró con minociclina o inhibidor de P2X7.
  • Los comportamientos similares a la depresión, indicados por un aumento del tiempo de inmovilidad y la latencia, se atenuaron con ambos tratamientos en ratas alimentadas con HFD.

Conclusiones:

  • La inhibición de P2X7 y la minociclina demuestran efectos antiinflamatorios en ratas obesas sometidas a desafío inmunitario.
  • Ambos tratamientos restauraron eficazmente la neurogénesis y mejoraron los comportamientos similares a la depresión en ratas alimentadas con HFD.
  • La focalización de P2X7 ofrece una estrategia terapéutica potencial para la depresión relacionada con la obesidad inducida por la dieta.