Prof. Edward Stern of the Neuronal Circuitry and Neurodegenerative Disease Laboratory and the Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center is focused on the processing of information in neuronal circuits in the mammalian brain, particularly the cerebral cortex and basal ganglia.
Stern is specifically interested in the changes in neuronal structure, function and circuitry that occur in neurodegenerative diseases such as Alzheimer’s Disease, Huntington’s Disease, and Parkinson’s Disease.
Disruptions in the structure and function of specific neurons and connections underlie the specific neurological symptoms associated with each disease, such as dementia, memory loss, and tremor.
Using advanced electrophysiological and imaging methods, Stern and his research team monitor the effects of the disease process in the intact brain.
In addition to providing a more complete understanding of neuronal operations in the normal and diseased brain, these methods allow them to apply novel therapeutic approaches such as passive immunotherapy to reverse the effects of the disease progress. Stern’s group has shown that some of the effects of the disease process can be halted and even reversed.
The major neuropathological hallmarks of Alzheimer’s Disease (AD) are extracellular plaques and intracellular tangles in the neocortex and hippocampus. The proteins that comprise these pathological features are amyloid-β and tau, respectively.
Using transgenic animal models that overexpress these proteins, Stern and his team measure their effects on neuronal activity of neocortical neurons, as well as measuring the effects of the aggregated proteins on neuronal structure.
Using in vivo multiphoton imaging, they have quantified the effects of amyloid-β plaques on neuronal structure.
In addition, using passive immunotherapy to clear amyloid-β plaques, they have found that the neurons are capable of recovery from the structural effects of plaque accumulation. This demonstrates a degree of neuronal plasticity in the aged, pathological brain that was not previously observed.
Huntington’s disease is a movement disorder characterized by choreic movements and decline in cognitive function. It is caused by a single autosomal-dominant gene located on the short arm of chromosome 4.
This gene codes for the amino acid glutamine (CAG), and is repeated multiple times, hence called polyglutamine. An abnormally large number of repeats results in the disease.
Polyglutamine accumulates within the neurons of the neocortex and neostriatum, resulting in abnormal activity and neuronal death.
Using transgenic mouse models of the disease, Stern’s research team measures the physiological effects of the polyglutamine accumulation in these neurons prior to cell death, in the hope of finding the mechanisms underlying the symptoms of the disease, and therefore enabling the amelioration or reversal of the symptoms.