Unlikely sea creature sheds light on brain disorders
Researchers at the Marine Biological Laboratory in Woods Hole study sea creatures to better understand life processes, which sometimes leads to scientific and medical breakthroughs. One scientist is studying how one such organism – the lamprey – may hold clues to why certain people fall prey to neurological diseases like Parkinson’s and Alzheimer’s.
Lampreys – eel-like parasitic fish that are among our earliest vertebrate relatives – possess a nervous system with amazing attributes. Unlike humans, they can regenerate their spinal cord if it is severed. Furthermore, lampreys possess comparatively huge axons, the long arm of the nerve cell or neuron used to transmit a signal to another cell. In humans, axons are a mere micron, or 0.000039 inches, in diameter, said Jennifer Morgan, Ph.D., an associate scientist at the Marine Biological Laboratory in Woods Hole, and director of its Eugene Bell Center for Regenerative Biology and Tissue Engineering. In lampreys, some of the axons measure 20-80 microns in diameter.
“Because they’re big, ….and also near the surface (of the spinal cord), they’re experimentally easy to access,” she said.
Lampreys’ large axons use the same neurotransmitter chemicals that human nerve cells do to communicate across a synapse – the microscopic gap between two nerve cells – thereby making them good animal subjects for study of synapses.
It is in the synapse that Morgan’s work focuses. She recently received a five-year, roughly $2.5 million grant from the National Institutes of Health to examine why a protein called alpha-synuclein accumulates in the brain synapses of people with Parkinson’s disease, Lewy body dementia and some forms of Alzheimer’s disease and how that affects synapse function.
According to Morgan, in normal neurons this protein apparently assists with recycling of synaptic vesicles – little packets in the cell that release neurotransmitters by fusing with the cell membrane and emptying their contents into the synapse during the transfer of a nerve impulse. But in these degenerative diseases, molecules of alpha-synuclein link together and form clumps at the synapse, and empty vesicles are not moved back inside the cell to be refilled with neurotransmitters, but rather get stuck in the synaptic membrane.
“The vesicles that contain the neurotransmitters go away,” Morgan said. “It happens very quickly and very acutely.”
The cells “run out of vesicles,” she continued, and neurotransmission stops.
Morgan said scientists had previously known that alpha-synuclein builds up in the body of diseased neurons, but more recently learned it also builds up in synapses.
“In Parkinson’s disease, you have a mutation in a gene for alpha-synuclein, and what happens is that over time, and in an age-related manner through a mechanism which we don’t yet understand, this alpha-synuclein protein will start to aggregate and build up in the neuron,” Morgan said. “And everyone was looking near the nucleus, in the cell body, the big part of the neuron, and you get these big aggregates of protein. And I thought that was kind of curious, because actually alpha-synuclein in its normal function is down at the synapse.”
“We don’t know its normal function quite as well as we’d like to now, but we do know that it’s involved in synaptic transmission,” she said of alpha-synuclein. “We don’t know as much about its normal function as we do about its pathological function.”