Accession Number : AD1011484

Title :   Role of CTGF in White Matter Development in Tuberous Sclerosis

Descriptive Note : Technical Report,01 Feb 2013,31 Jan 2016

Corporate Author : Boston Childrens Hospital Boston United States

Personal Author(s) : Sahin,Mustafa

Full Text :

Report Date : 01 Apr 2016

Pagination or Media Count : 13

Abstract : Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder caused by loss of either TSC1 or TSC2function(Tsai and Sahin, 2011). TSC affects 1/6,000 individuals worldwide and affects multiple organs including the brain, skin, eyes, kidneys, heart, and lungs (Crino et al., 2006). TSC patients present with epilepsy (90 ), intellectual disability and autism(50 ), and other disorders including sleep disruption, attention-deficit hyperactivity disorder, and anxiety(Han and Sahin, 2011). The neuropathological findings in TSC are cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGAs) (DiMario, 2004). Another important yet not well-studied feature of TSC pathology in brain ishypomyelination (Ridler et al., 2001). Most recently using diffusion tensor imaging we observed abnormal white matter microstructure in patients with TSC that have autism compared to TSC patients without autism (Lewis et al., 2013; Peters et al.,2013). To uncover the underlying molecular mechanisms of hypomyelination in TSC, we investigated the role of neuronal factors affecting oligodendrocyte development in our Tsc1cc;SynICre mouse model, which lacks Tsc1 expression only in neurons. Here we show that, neurons lacking Tsc1 secrete excessive amounts of connective tissue growth factor (CTGF), which in turn blocks the maturation of oligodendrocytes, and thus myelination both in vitro and in vivo.

Descriptors :   brain , mice , sclerosis

Distribution Statement : APPROVED FOR PUBLIC RELEASE