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Scientists measure communication between stem cell-derived motorneurons and muscle cells by 123wert sdfsf
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Scientists measure communication between stem cell-derived motorneurons and muscle cells by 123WERT SDFSF
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| Article Posted: 04/01/2013 |
| Article Views: 112 |
| Articles Written: 2217 - MORE ARTICLES FROM THIS AUTHOR |
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Scientists measure communication between stem cell-derived motorneurons and muscle cells |
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In an effort to identify the underlying causes of neurologicaldisorders that impair motor functions such as walking andbreathing, UCLA researchers have developed a novel system tomeasure the communication between stem cell-derived motor neuronsand muscle cells in a Petri dish. The study provides an important proof of principle that functionalmotor circuits can be created outside of the body using stemcell-derived neurons and muscle cells, and that the level ofcommunication, or synaptic activity, between the cells could beaccurately measured by stimulating motor neurons with an electrodeand then measuring the transfer of electrical activity into themuscle cells to which the motor neurons are connected. When motor neurons are stimulated, they release neurotransmittersthat depolarize the membranes of muscle cells, allowing the entryof calcium and other ions that cause them to contract. By measuringthe strength of this activity, one can get a good estimation of theoverall health of motor neurons. That estimation could shed lighton a variety of neurodegenerative diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis , or Lou Gehrig's disease , in which the communication between motor neurons and muscle cellsis thought to unravel, said study senior author Bennett G.
Novitch,an assistant professor of neurobiology and a scientist with the Eliand Edythe Broad Center of Regenerative Medicine and Stem CellResearch at UCLA. The findings of the study appear in PLoS ONE , a peer-reviewed journal of the Public Library of Science. "Now that we have this method to measure the strength of thecommunications between motor neurons and muscle cells, we may beable to begin exploring what happens in the earliest stages of motor neuron disease , before neuronal death becomes prevalent," Novitch said. "This canhelp us to pinpoint where things begin to go wrong and provide uswith new clues into therapeutic interventions that could improvesynaptic communication and promote neuronal survival." Novitch said the synaptic communication activity his team was ableto create and measure using mouse embryonic stem cell-derived motorneurons and muscle cells looks very similar what is seen in amouse, validating that their model is a realistic representation ofwhat is happening in a living organism.
"That gives us a good starting point to try to model what happensin cells that harbor genetic mutations that are associated withneurodegenerative diseases,. To do that, we had to first define anactivity profile of normal synaptic communication," he said. "Someresearch suggests that a breakdown in this communication can be anearly indication of disease progression or possibly an initiatingevent. Neurons that cannot effectively transmit information tomuscle cells will eventually withdraw their contacts, causing boththe neurons and muscle cells to degenerate over time. Hopefully, wecan now create disease models that will allow us to study what ishappening." In this study, Novitch and his team, led by Joy Umbach, anassociate professor of molecular and medical pharmacology, usedmouse embryonic stem cells to create the motor neurons and previously established lines ofmuscle precursors to produce muscle fibers.
They put both cellstogether in a Petri dish, and the cells were cultured in such a wayto encourage communication. Novitch said the team wanted to see ifthey would naturally form synaptic contacts and whether or notthere was neural transmission between them. In less than a week, the neurons had reached out to the musclecells and assembled the protein networks needed for synapticcommunication, Novitch said. To measure the connections between the cells, the scientists used atechnique called dual patch clamp recording.
Pipettes containingstimulating and recording electrodes are inserted into themembranes of the motor neurons and muscle cells, being careful notto injure them. With this method, they were able send an electricalcurrent into the motor neurons and measure responses in the musclecells, as well as visualize the muscular contractions. "The in vitro system developed here might accordingly be expandedto assess the underlying cellular and molecular mechanisms thatcontribute to this decline in synaptic input to motor neurons," thestudy states. "Thus, in addition to their utility for helping toanswer fundamental biological questions, these co-cultures haveclear applications in addressing problems of medical significance." Going forward, Novitch and his team hope to recreate and confirmthe work using human stem cell-derived motor neurons and musclecells and measure the synaptic communications with newly developedoptical recording methods, which are less invasive than the patchclamp techniques used in this study.
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