Accession Number:

ADA621181

Title:

Altered Astrocyte-Neuron Interactions and Epileptogenesis in Tuberous Sclerosis Complex Disorder

Descriptive Note:

Annual rept. 1 Jun 2014-31 May 2015

Corporate Author:

COLUMBIA UNIV NEW YORK

Personal Author(s):

• Sulzer, David

Report Date:

2015-06-01

Pagination or Media Count:

9.0

Abstract:

This report is on the second year of our 2011 Tuberous Sclerosis Complex Research Program Idea Development Award 0712-615. The original goals are to explore the potential mechanism for epileptogenesis in Tuberous Sclerosis Complex TSC disease, with a focus on altered astrocyte-neuronal interactions caused by astrocyte-specific TSC deficiency. Our hypothesis is that abnormal cells in non-tuber cortex might form an abnormally excitable network that underlies seizure generation in TSC. Epileptogenesis in non-tuber neural tissue in TS may thus arise by an imbalance of decreased inhibitory and increased excitatory synaptic transmission. Astrocytes could also regulate neuronal excitability by glutamate uptake and other means that alter expression and function of synaptic receptors for glutamate, or by altering the number of synapses. A deficiency of GABAergic interneurons, a possible downstream consequence of altered mTOR activity in astrocytes, may further contribute to the early onset and severity of seizures in TS.

Descriptors:

• *ASTROCYTES
• *CONVULSIVE DISORDERS
• *ELECTROPHYSIOLOGY
• *EPILEPSY
• ABNORMALITIES
• CLINICAL MEDICINE
• EXCITATION
• GENE EXPRESSION
• GLUTAMIC ACID
• INHIBITION
• MICE
• MOTOR NEURONS
• NEUROSCIENCE
• PHOSPHORUS TRANSFERASES
• PROTEINS
• RECEPTOR SITES(PHYSIOLOGY)
• RESPONSE(BIOLOGY)
• SYNAPSE
• TISSUES(BIOLOGY)
• TRANSMITTANCE

Subject Categories:

• Biochemistry
• Anatomy and Physiology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE