Jeffery A. Lowell, M.D. champions organ donation awareness		Search View past issues

Welfare use more common than many think Many Americans believe that welfare use happens to someone else, to people outside of mainstream society. But a study published in a recent issue of Social Work casts considerable doubt on that notion, finding that nearly two-thirds of all Americans between 20 and 65 will at some point turn to a public assistance program. Full story More Stories
				Mouse model mimics natural development of epilepsy By Gila Z. Reckess Gutmann School of Medicine researchers have developed a mouse model of the genetic disorder tuberous sclerosis complex (TSC). The mice develop epilepsy within the first few months of life, mimicking one of the most devastating complications of TSC in children. This research represents one of the first animal models of epilepsy that does not require toxic injections or injury and results from a single gene defect. The study appears online in Annals of Neurology and will be published in the journal's September issue. "What's enormously exciting about this study is the potential to employ this mouse model as a pre-clinical model for TSC-related epilepsy," said David H. Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology. "In addition, we disrupted a gene for TSC in one of the brain's support cells, called astrocytes, instead of in the brain's main communication cells, neurons. Our results therefore shed light on the contribution of cells other than neurons to the development of seizures and epilepsy." Gutmann led the study in conjunction with Kelvin Yamada, M.D., associate professor of neurology and pediatrics. TSC is a genetic disorder that affects about 50,000 Americans, more than half of whom experience frequent debilitating epileptic seizures. TSC also causes tumors to form in various organs, including the brain. Physicians cannot cure the disease nor can they predict which individuals will experience severe symptoms. Scientists have identified two genes responsible for TSC --TSC1 and TSC2. Because affected individuals often develop brain tumors, Gutmann's team hypothesized that TSC1 may provide a clue into tumor development. Because mice that completely lack TSC1 die early in development, the researchers engineered a strain of animals that are missing the TSC1 gene in only one type of brain cell: astrocytes. Surprisingly, the mice did not develop tumors; instead, they developed epilepsy. Mice without astrocyte TSC1 began exhibiting abnormal movements and posture around two months after birth. They occasionally became rigid, fell over and began to shake their heads and limbs, behaviors characteristic of seizures. To determine if these episodes were in fact seizures, the team recorded brain activity in affected animals and in normal mice using electroencephalography (EEG). EEG recordings verified that the affected mice had frequent seizures and the normal mice did not. Moreover, brain slices from these mice lacking TSC1 in astrocytes revealed other abnormalities. The animals had larger brains with far more astrocytes. Most surprisingly, deleting TSC1 in astrocytes evoked changes in another type of brain cell: neurons. Within the first five weeks after birth, mice had abnormally organized collections of neurons in the hippocampus -- a region involved in human epilepsy. "In our model, the loss of TSC1 expression in astrocytes translated over time into defects in neuronal function and eventually led to epilepsy in mice," Yamada said. "We're very excited about this discovery because it may help us understand how seizure disorders develop, both in TSC and in other kinds of epilepsy."

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