Central Nervous System Diseases; Nervous System Malformations; Nervous System Diseases; Neurologic Manifestations; Diseases
Stem Cell Center, Yale: Stem Cell Niche and Homing
The brain is a wonderful and mysterious machine, which makes us who we are. The activity of billions of neurons and glia orchestrate our thoughts and daily life. However, alterations in the number of neurons, their misplacement, or changes in the way they receive, handle, or send information can negatively impact our brain function and our lives. A mutation in a single gene can lead to such alterations resulting in a specific pathology and disorder. Our Mission is to understand how a mutated, dysfunctional protein will lead to abnormal brain formation and function.
Extensive Research Description
Our attention has been focused on the mammalian Target of Rapamycin, mTOR. mTOR is a converging point in cell signaling, or in other terms an intracellular hub, that receives signals from diverse intracellular routes and extracellular ligands. Importantly, mTOR is dysregulated in many neurological disorders. These disorders referred to as mTORopathies include (but are not limited to) Tuberous Sclerosis Complex (TSC), autism, Alzheimer's disease, and Schizophrenia. We have focused on TSC, to better understand the circuit basis of mental retardation and autism.
Our work has the following three lines of research related to the following keywords: mTOR- Neural stem cell- Neurogenesis-Cognitive functions- mTORopathies
1. Understanding how a circuit is formed from neural stem cells to synaptic integration in health and in developmental mTORopathies.
2. Preventing lesion formations and associated neurological symptoms in TSC and other developmental mTORopathies.
3. Understanding the molecular basis of cognitive dysfunctions in TSC.
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- Platel JC, Dave KA, Lacar B, Gordon, V, Rubio ME, and Bordey A. NMDA receptors activated by glutamate released from astrocyte-like cells are critical for postnatal subventricular neurogenesis. Neuron. (2010) 65:859-872.
- Young SZ and Bordey A. GABA's control of stem and cancer cell proliferation in adult neural and peripheral niches. Physiol, 24:171-85, 2009.
- Wang DD and Bordey A. The astrocyte odyssey. Prog Neurobiol, 86(4):342-67, 2008.
- Liu X, Wang Q, Haydar TF, Bordey A. Nonsynaptic GABAergic signaling in the postnatal subventricular zone controls GFAP-expressing cell proliferation. Nature Neurosci, 8:1179-87, 2005.