Understanding the Role of TSC1/2 in Cerebellar Purkinje Neurons
Abstract
Tuberous sclerosis complex is a multisystem autosomal dominant disorder caused by mutations in either TSC1 or TSC2genes. Previously our group has shown that Tsc1 knock-out mice Purkinje cells are involved in the development of autistic-like features for these mice. In addition, at BCH we have collected fibroblasts and derived pluripotent stem cell lines from TSC-patients and unaffected familial controls. We have developed differentiation protocol for generation of human Purkinje cells from iPSCs. We have studied mTOR-pathway hyperactivation in TSC2-deficient patient iPSC-derived PCs compared to control cells. We are also analyzing the proliferation and differentiation rate of TSC2-deficient neural precursor cells compared to control cells and studying electrophysiological properties of TSC2-deficient iPSC derived Purkinje cells. According to our preliminary functional data, the TSC-patient iPSC-derived PCs and healthy control iPSC-derived PCs exhibit GABAergic inhibitory synaptic currents, which can be blocked with bicuculline. These cells also exhibit glutamatergic excitatory synaptic currents, which can be blocked with CNQX. The disease phenotyping with TSC deficient iPSC-derived PCs is important for the future development of new pharmacotherapy for TSC-patients with autism.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2016
- Accession Number
- AD1020472
Entities
People
- Mustafa Şahin