Lagrange, Andre, Department of Neurology
Andre H. Lagrange, M.D., Ph.D.
Associate Professor of Neurology
6144 MRB III
My lab uses electrophysiological techniques with brain slices and immortalized cultured cells to study the tuning of inhibitory neurotransmission during normal brain function and in disease states, including epilepsy. GABA is the primary inhibitory neurotransmitter in the adult brain and is critical for normal brain function. However, in the developing brain, GABA acts as an excitatory signal that directs normal neuronal migration and synaptogenesis. We have found that a predominant GABA receptor expressed primarily during early life is subject to RNA editing in a developmentally regulated fashion. By introducing a single amino acid change in a key portion of these GABA receptors, RNA editing leads to significant changes in receptor function, thereby producing a brief window in late embryogenesis/early postnatal life in which GABA causes the prolonged/slow depolarizations that are important for the subsequent formation of both excitatory and inhibitory connections later in life.
Lagrange’s clinical interest is in the treatment of women with epilepsy. It has been known for a few years that some of the medications used to treat epilepsy may increase the risk of having a child with congenital malformations. Unfortunately, these teratogenic drugs are also widely used for a number of other neurological and psychiatric disorders, such as migraines and bipolar disorder. Alarmingly, recent work has suggested that children exposed to a subset of these drugs in utero have reduced IQ later in life, and an increased incidence of neurodevelopmental disorders such as autism. Further animal work has suggested that these poor cognitive outcomes may involve subtle cortical malformation/laminar disruption, which are thought to be mediated by the GABA modulatory nature of these drugs. Lagrange’s lab is working to understand the role of specific GABA receptors in brain development and how these processes are regulated during normal development, as well as how they may be disrupted by disease states and medications.