Organizing a symphony has a lot more to do with brain function than many believe, and like the musical performance, a loud disruption can cause confusion and disorder.
Alzheimer’s disease is a neurodegenerative disease in humans that causes loss of short-term and long-term memory, difficulty performing simple tasks, personality changes and confusion.
Biology and biochemistry assistant professor Jokubas Ziburkus was awarded a $100,000 grant from the Alzheimer’s Association for the next two years for his study on the neuron-level for Alzheimer’s disease.
“Very little is known about when and where the initial ‘breakdown’ of neural network function occurs,” Ziburkus said in an email.
“The brain networks are very complex and are uniquely comprised of the variety of neuronal subtypes that fall under the umbrella of the major classification of neurons – inhibitory and excitatory. Neurons communicate with each other via electrochemical means, where a release of a chemical neurotransmitter is initiated by the changes in neuronal electrical potentials.”
“These changes in electrical activity work in wave pattern or via oscillation,” Ziburkus said.
Plaques, or protein aggregates, occur in certain regions of the brain and are correlated with increased short-term memory loss in the mouse models used in this research, said Jason Eriksen, assistant professor of pharmacology and a collaborator in Ziburkus’ research.
“The question is ‘Why does this happen?’ And so we think this work explains some of the memory,” Eriksen said.
These plaques may cause a disruption in the carefully conducted electrical symphony, Eriksen said. The work that Ziburkus and Eriksen did shows a correlation between plaques and overly sensitive neural activity.
“The theory was that this formation of plaques disorders this symphony. We had thought that it damages or disrupts this activity. How do we tell that? We can’t talk to the mouse. We know from behavior that we see this loss of memory,” Eriksen said.
The hippocampus is the part of the brain that handles short-term memories, Eriksen said. The transgenic mouse, instead of showing decreased electrical activity, shows an increased and unchecked amount of signal.
“This can be envisioned almost like a seizure,” Eriksen said.
“It’s a hyper-excitable brain, which is not something you think of when you think of Alzheimer’s.”
This “seizure” is shown in areas of the brain with these protein clumps. The next step is to figure out what part of the brain cells in those areas are being affected. The two UH professors and the undergraduate and graduate students they worked with reached out to Baylor College of Medicine.
“Neurons have parts of their cell that are excitable. That means they respond to or generate electrical signals. One hypothesis that Alzheimer’s may be caused by disruption of these important domains,” said Baylor neuroscience professor Matthew Rasband.
Many neurodegenrative diseases like Huntington’s disease involve protein clumps. Nobody truly understands why these nerve cells stop working, Rasband said, but there is a hypothesis.
“One very simple way to cause a neuron to not work properly is to disturb these excitable domains. The main region of the cell that we’re looking at is called the axon initial segment,” Rasband said.
The next step for the research Rasband and his UH colleagues are doing is to figure out what is happening in this excitable domain. If a discovery is made, it could prove useful in finding treatment or relief for those suffering with Alzheimer’s and other neurodegenerative disease treatment, Rasband said.
“The work related to the axon initial segment is still ongoing,” Rasband said, “but far down the line, study of this disruption could lead to therapies for Alzheimer’s or other diseases that involve neuron dysfunction due to plaques.”