April Neal, a fifth-year PhD student majoring in Environmental Health Sciences, with a sub-specialty in neurotoxicology was awarded second place in the predoctoral poster competition at the International Neurotoxicology Conference. Her faculty mentor was Tomas Guilarte, PhD.

Pictured with April are Tomas Guilarte (left) and Dr. Morris Cranmer, who has funded the Neurotoxicology Conference Student Awards for the past 25 years.

Her research project is entitled "Disruption of Developing Glutamatergic Synapses by Pb2+."

April discusses her research below:
"My thesis research is on the effects of chronic lead exposure during synaptogenesis in developing hippocampal neurons. We have transitioned to a primary culture system that allows us to determine structural changes that occur in both the pre-synaptic
active zone (PAZ), as well as the post-synaptic density (PSD) during lead exposure.

Using confocal microscopy, live imaging and western blots we have determined that key presynaptic proteins essential for vesicular release are reduced after lead exposure. These protein changes result in significant functional impairment of pre-synaptic vesicular release in lead exposed neurons.

Furthermore, lead exposure results in altered N-methyl-D-aspartate receptor (NMDAR) targeting; specifically, there are increased levels of NR2B-containing receptors found in the PSD after lead exposure.

Finally, we have shown that both the pre- and post-synaptic effects of lead exposure are due to chronic inhibition of the NMDAR by lead. We believe that the underlying mechanism of these changes is disruption of NMDAR activity-dependent retrograde signaling essential for coordinated maturation of both sides of the synapse.

Current studies are underway to determine whether the signaling of two candidate molecules, brain-derived neurotrophic factor (BDNF) and nitric oxide (NO), are disrupted after lead exposure."