Un estudio establece la relación entre los neurotransmisores y trastornos como el autismo o la ansiedad
Un estudio del Instituto de Neurociencias UMH-CSIC establece la relación entre los neurotransmisores y trastornos como el autismo o la ansiedad – Servicio de Comunicación
Patologías como los trastornos del espectro autista, la esquizofrenia o la ansiedad tienen una base común: el desequilibrio entre los neurotransmisores excitadores e inhibidores. Esta es una de las conclusiones de un estudio realizado por el grupo de Fisiología Sináptica del Instituto de Neurociencias, centro mixto de la Universidad Miguel Hernández (UMH) de Elche y el Consejo Superior de Investigaciones Científicas (CSIC). Este estudio, dirigido por el investigador Juan Lerma, señala que la forma del cerebro afectada por ese desequilibrio determina la patología y los síntomas asociados a ella. La investigación ha sido publicada en la revista “Cell Reports”.
Un estudio del Instituto de Neurociencias UMH-CSIC establece la relación entre los neurotransmisores y trastornos como el autismo o la ansiedad
Un estudio del Instituto de Neurociencias UMH-CSIC establece la relación entre los neurotransmisores y trastornos como el autismo o la ansiedad – Servicio de Comunicación
Patologías como los trastornos del espectro autista, la esquizofrenia o la ansiedad tienen una base común: el desequilibrio entre los neurotransmisores excitadores e inhibidores. Esta es una de las conclusiones de un estudio realizado por el grupo de Fisiología Sináptica del Instituto de Neurociencias, centro mixto de la Universidad Miguel Hernández (UMH) de Elche y el Consejo Superior de Investigaciones Científicas (CSIC). Este estudio, dirigido por el investigador Juan Lerma, señala que la forma del cerebro afectada por ese desequilibrio determina la patología y los síntomas asociados a ella. La investigación ha sido publicada en la revista “Cell Reports”.
Para mantener una función cerebral adecuada es necesaria una buena regulación del equilibrio entre la transmisión sináptica (comunicación entre las neuronas) excitatoria e inhibitoria, que serían el equivalente al acelerador y el freno, respectivamente, del sistema nervioso. Esta regulación tan precisa se logra con la liberación de las dosis adecuadas de neurotransmisores de uno u otro tipo en los puntos de contacto entre las neuronas, las sinapsis.
Cuando ese equilibrio se rompe aparecen patologías aparentemente tan diferentes como la ansiedad, depresión, esquizofrenia, trastorno bipolar o trastornos del espectro autista.
Alteraciones en el material genético como las duplicaciones pueden dar lugar a la pérdida o ganancia de la función de determinados genes que pueden afectar a ese equilibrio entre los neurotransmisores excitadores e inhibidores por la producción excesiva de proteínas.
Es lo que ocurre con el gen Grik4, esencial para regular la afinidad de un tipo de receptores del neurotransmisor excitador glutamato, tal y como demuestra una investigación del grupo de Fisiología Sináptica del Instituto de Neurociencias UMH-CSIC.
La investigación que publica la revista “Cell Reports” apunta a que las alteraciones del comportamiento que caracterizan a las patologías antes mencionadas pueden tener un mecanismo común: un exceso en la tasa de liberación del principal neurotransmisor excitatorio del sistema nervioso central, el glutamato. Además, afirma que las manifestaciones que caracterizan a cada una de ellas dependerían del área del cerebro afectada por ese desequilibrio.
El grupo de Fisiología Sináptica que dirige el investigador Lerma ha comprobado que un aumento leve de la dosis del gen Grik4 lleva a un desequilibrio persistente en la actividad excitatoria e inhibitoria que repercute en la adecuada respuesta de la amígdala cerebral, una estructura que procesa emociones como el miedo o la ansiedad. “Hemos reproducido en modelos de ratón la duplicación de un fragmento del cromosoma 11, que contiene el gen Grik4 y se sabe ocurre en el autismo y hemos visto que tiene un efecto en el comportamiento de los ratones semejante al que ocurre en humanos. Los roedores portadores de esta duplicación muestran signos de depresión, ansiedad y alteraciones de la conducta social características de las personas con trastornos del espectro autista”, ha explicado el nvestigador Lerma.
Este mismo gen, Grik4, implicado en la regulación de la afinidad de los receptores de la sinapsis por el glutamato, también está relacionado con el trastorno bipolar. En concreto se sabe que las personas que presentan una deleción normal de un segmento de la zona reguladora de este gen tienen mayor cantidad de la proteína y poseen menor riesgo de desarrollar esta enfermedad.
Esta variación en la cantidad de proteína está presente en el 50% de la población y cuando el segmento está presente se producen RNAs menos estables, por lo que hay menor cantidad de proteína, lo que confieren mayor susceptibilidad a desarrollar el trastorno bipolar. Con este trabajo, el grupo del profesor Lerma ha demostrado que “cambios mínimos en la intensidad de la transmisión sináptica provocan modificaciones importantes en el comportamiento cuando tienen lugar en circuitos determinados del cerebro.
A diferencia de lo que recogen los manuales como el DSM-V o la última edición del CIE desde un enfoque neurocientífico, muchos trastornos psiquiátricos formarían parte de un continuo. “El trabajo que acabamos de publicar ayuda a entender que esas enfermedades se deben a la misma alteración y que los efectos serán distintos según la zona del cerebro donde ocurra la sobreexpresión génica, que rompe el equilibrio entre excitación e inhibición”, matiza Lerma.
A estas conclusiones han llegado gracias al modelo de ratón que han desarrollado, con la inserción en el genoma de copias extras del gen Grik4 como ocurre en el autismo y han observado que tiene efecto en el comportamiento parecidos a lo que ocurren en humanos.
Ese desequilibrio que lleva al incremento en la actividad sináptica se produce por un aumento en la afinidad de los receptores presinápticos, cuya consecuencia es una estimulación de la liberación de glutamato. Esto se traduce en un cambio en la intensidad de la transmisión sináptica en dos circuitos importantes de la amígdala. Si ocurre en el ansiolítico, se reduce su actividad, y por tanto se genera mayor nivel de ansiedad. Y si afecta al circuito del miedo, se produce más miedo y depresión.
Finalmente, los investigadores han podido revertir tanto los síntomas funcionales como los comportamentales, corrigiendo la cantidad de proteína al normalizar la dosis génica en los ratones. Para ello, han cruzado el modelo de ratón transgénico que han desarrollado, portando copias extras del gen Grik4 con otro que carece del gen (ratón knock-out). Sin embargo, aunque estas patologías se han logrado corregir en el laboratorio, aún se está muy lejos de una aplicación clínica.
Como conclusión, el investigador Lerma ha destacado que “la dosis génica importa cuando se trata de enfermedades mentales. Incluso en condiciones normales, las variaciones en la cantidad de proteínas codificadas por nuestros genes nos diferencian y nos hacen únicos, aun sin llegar a desarrollar patologías”.
Fuente: Servicio de Comunicación Universitas Miguel Hernández
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