Así actúan los genes del autismo en el cerebro

Una nueva investigación halla los genes específicos del autismo y determina su grado de implicación en la diversidad del TEA, lo que ahora podría utilizarse para dar con nuevos tratamientos.

En el trastorno del espectro autista (TEA) hay implicados entre 600 y 1.200 genes de riesgo de los que se conocen una infinidad de variedades.

Ninguna produce por sí misma esta alteración del sistema nervioso, ni se sabe cómo se combinan, en qué grado afectan o qué relaciones tienen con otras enfermedades. Para entender el mapa completo del autismo, los científicos utilizan herramientas genéticas que descifran cada pieza de este complicado puzzle.

El último avance lo ha presentado un grupo de investigadores de la universidad estadounidense de California en San Francisco (UCSF). Su punto de partida no se ha centrado en quiénes son estos genes, sino en qué producen, para detectar anomalías en las células del cerebro.

Han utilizado la técnica de secuenciación de una única célula sobre tejido nervioso de pacientes con TEA y han analizado todo su ARN, el brazo ejecutor del ADN, la molécula que recibe la orden de los genes.

Así, han encontrado que la gravedad clínica del TEA está relacionada con las alteraciones a nivel molecular de un tipo concreto de neuronas y de los circuitos cerebrales. De esta forma, han dado con genes específicos del autismo y han determinado su grado de implicación en la diversidad del TEA, lo que ahora podría utilizarse para dar con nuevos tratamientos.

El estudio lo ha dirigido Arnold Kriegstein (catedrático de neurología de la UCSF) y lo ha publicado este jueves la revista científicaScience. En él han participado 31 personas de entre 4 y 22 años (15 pacientes con TEA y 16 sin esta afección) y 41 donantes de los que se han extraído muestras de tejido postmortem.

La investigación se ha completado con la base de datos 10X Genomics, de la que se han consultado 104.559 perfiles (52.003 pacientes con TEA y 52.556 sin este trastorno). De ellos se han observado 1.391 genes y 2.213 transcripciones (productos derivados de estos genes).

Como ninguno de los pacientes con TEA había sido diagnosticado con discapacidad intelectual, pero la mitad de estos pacientes habían sufrido episodios de convulsiones (una afección común en los trastornos del espectro autista), los científicos han incluido en su investigación a ocho pacientes con epilepsia esporádica, siete sin ella y los datos de 21.984 perfiles de la base de datos 10X Genomics. Estos datos han servido para esclarecer la relación entre epilepsia y TEA.

Los resultados profundizan en la idea de que no existe un único gen o grupo de genes que provoque autismo, pero revela los que están implicados, hasta dónde lo están y a qué células afectan. Lo que han visto es que estos genes alteran las neuronas del córtex cerebral, alterando su crecimiento y migración.

También modifican los circuitos neuronales mediante cambios en las moléculas que dirigen la forma en la que las neuronas se comunican: la psinapsis. Además, las neuronas que quedan afectadas durante el desarrollo fetal, desencadenan luego una cascada molecular que modificará las neuronas maduras.

VARIAS CÉLULAS AFECTADAS

Entre las células afectadas se encuentran las neuronas excitadoras de tipo L2 / 3, las neuronas L4, las interneuronas VIP, los astrocitos protoplásmicos y la microglia. De todas ellas, los cambios que alteran a las neuronas L2 / 3 y la microglía son los que se corresponden con la mayor gravedad clínica del TEA, mientras que la mayoría de los pacientes coinciden en que presentan anomalías de la expresión de los genes de las neuronas de proyección cortico-cortical superior (L2 / 3) y de capa profunda (L5 / 6-CC). Para explicar las variedades conductuales del TEA, Kriegstein y sus colegas apuntan a una anomalía en la regulación de una serie de genes de las neuronas de proyección de la capa superior del córtex.

En cuanto a la epilepsia, ésta sólo comparte un 10% de todas las modificaciones de las expresiones genéticas que existen en el TEA. Cuando ambos trastornos están presentes, las neuronas más afectadas son las L5 / 6 y un cierto tipo de interneuronas, lo que indica que las alteraciones provocadas por los genes identificados para el TEA no se deben a las convulsiones.

Con este estudio, el trastorno del espectro autista ha ganado miles de moléculas para ahondar en su origen, pero esa búsqueda puede centrarse ahora en cierto tipo de neuronas y genes. 

En Europa la prevalencia del TEA es de un 1% de nacimientos, una cifra en la que hay más hombres que mujeres y que aumenta drásticamente al crecer el número de diagnósticos practicados, como en Estados Unidos, donde ocurre en un 1,6%.

El autismo se caracteriza por una modificación del desarrollo neurológico del paciente que produce problemas en la comunicación e interacción social, conductas repetitivas o intereses restringidos. 

El cuadro clínico es muy heterogéneo, por lo que suele referirse a esta afección como trastorno del espectro autista (TEA). En su investigación se están teniendo en cuenta desde variaciones genéticas puntuales o hereditarias hasta factores ambientales.

fuente: https://www.elmundo.es/ciencia-y-salud/salud/2019/05/16/5cdd9f3dfc6c836f5b8b463b.html

Esta entrada fue publicada en AUTISMO, DIVULGACIÓN. Guarda el enlace permanente.

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