Cell Type-Specific Contributions to the TSC Neuropathology
Abstract
The goal of this work is elucidate the cellular and molecular mechanisms that cause neurological defects in tuberous sclerosis complex (TSC) patients. We are particularly interested in understanding the causes of epilepsy and cognitive dysfunction in the developing TSC brain. Several published studies demonstrated that cell-cell communication is important for proper synaptic connectivity and function. For example, inhibitory neurons and glial cells are known to modulate the activity of excitatory neurons and thus affect excitability and brain function. Excitatory neurons are the most abundant cell population in the developing cerebral cortex and the first cell type to be generated. How are they specifically affected by TSC mutations? How do mutated excitatory neurons influence the development of other brain cells? In this study, we want to better understand how the communication among different cell types is altered by TSC mutations. We reason that defects in synaptic activity and cognitive function may be ameliorated if we identify key factors that mediate not only abnormal neuronal development, but also faulty cell-cell communication in the developing TSC brain. In addition to synapse development, altered cell-cell interactions could also be relevant to the formation of cortical tubers and brain tumors and could lead to novel strategies to halt their growth or to induce their regression.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610415
Entities
People
- Gabriella D Arcangelo
Organizations
- Rutgers University
- United States Army