Pathology of autism in Rett syndrome
| NE-Munroe-Meyer Institute of Genetics & Rehabilitation, UCEDD/LEND | |||
| Program Type | LEND,UCEDD | Fiscal Year | 2016 |
| Contact | Jyothi Arikkath, Ph.D. | ||
| [email protected] | |||
| Phone | 402-559-8461 | ||
| Project Description | |||
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Rett syndrome is a devastating neurodevelopmental disorder associated with autism, epilepsy and intellectual disabilities. Common features associated with these are alterations in the structure and function of synapses. Synapses are points of communication between neurons. Several recent studies have found mutations in a gene called CDKL5 in Rett syndrome. However, we do not know what the normal functional role of cdkl5 is in neuronal development and how mutations contribute to the initiation or progression of Rett syndrome. In addition to neurons, the brain includes other cells called astrocytes. In the past several years, it has become clear that astrocytes are very important for neurons to generate and maintain synapses. Astrocytes help neurons to generate or maintain synaptic connections by either secreting factors or supporting neurons via contact based mechanisms. Our studies have identified a novel form of cdkl5 that is expressed in astrocytes. We propose a novel model in which we hypothesize that cdkl5 in astrocytes is important for controlling the structure and function of synapses in neurons. In Rett syndrome, this functional role of cdkl5 is compromised. This leads to alterations in the synaptic structure and function in neurons that then lead to the neural circuit abnormalities that manifest as autism and related disabilities. Identifying and characterizing the functional role of this novel form of cdkl5 in normal and Rett mutant astrocytes would allow us to devise novel therapeutic approaches for this devastating syndrome. |
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