"Early Deficits in Long-Term Potentiation in Huntington's Disease Knock-In Mice: Reversal with Brain-Derived Neurotrophic Factor (BDNF)" is a poster presentation that was given at the Cure Huntingon's Disease Initiative (CHDI) in Palm Springs, California (2/7/07). The study, which was done, in part, at the lab where I work - the lab of Dr. Gary Lynch at the University of California, Irvine - addresses a component of HD that has been so far largely ignored. This area is cognitive function (thinking and behavior). While it is known that HD causes problems with cognition, most HD research has focused on cellular energetics, aberrant protein aggregation and other cellular processes that go awry in HD leading to neuropathology and cell death in the striatum, the region of the brain responsible for planning and modulation of movement.

The present study looked at the brain region known as the hippocampus and investigated processes related to cognition. The hippocampus, which has been studied extensively in Alzheimer's disease, is known to regulate the consolidation of short term memory. Deficits in this area are known to result in various forms of dementia.

Dr. Lynch, the lab's principal investigator, has had an extensive career studying the hippocampus, in particular, its electrical properties (electrophysiology), and is largely responsible for the elucidation of a phenomenon known as Long-Term Potentiation (LTP). LTP is a change in the electrical properties of neurons that is responsible, in part, for the encoding of memory. (Specifically, LTP is the property of neurons to retain a heightened voltage potential after being stimulated by a series of electrical pulses.)

What is novel about this study is that LTP and another measure of memory encoding (actin polymerization) were found to impaired in HD mice. Actin polymerization, is the formation of the flexible skeleton within the neuron. It is only in the last couple of decades that actin polymerization has been related to memory, a result that is really rather amazing.

The exciting part of the study is that something has been found to reverse the deficits just mentioned. This something is Brain Derived Neurotrophic Factor (BDNF), a much studied protein that supports the survival of existing neurons and encourages the growth of new ones as well as neuronal interconnections (synapses). BDNF is the subject of intense scrutiny in the second lab to participate in the study, that of Dr. Christine Gall. When added to the HD hippocampus, BDNF restored both electrical properties of the cell (LTP) and its actin polymerization. By restoring these neural components, there is hope that BDNF, and compounds that regulate BDNF, may treat psychiatric aspects of the disease. Stay tuned, as you will almost certainly be hearing much more in the future about BDNF and other treatments of the cognitive aspects of HD.

Research Poster

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• Introduction
• Methods
• LTP is impaired in Hdh^Q92 and Hdh^Q111 mice
• Burst response facilitation is impaired in Hdh^Q111 mice
• Polymerized actin co-localizes with synaptic markers
• BDNF restores TBS-induced LTP and actin polymerization, but not burst response facilitation in Hdh^{Q111 mice}
• Conclusions