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Posts Tagged ‘Umbilical cord’


Optical Neurons

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Umbilical Cells Help Eye’s Neurons Connect

Factor released by cells helps connections, not longevity

“By learning more about how these cells work, we are one step closer to understanding the disease states in which these cells should be studied,” said Cagla Eroglu, an assistant professor of cell biology and neurobiology at the Duke University Medical Center, who led the research.
Umbilical cord tissue-derived cells (hUTC) differ from umbilical cord blood cells in that they are isolated from cord tissue itself, rather than the blood. The Duke
team used an established cell culture system to determine whether and how the hUTCs might affect the growth of neurons isolated from the retinas of rat eyes.
In an experimental setup that allowed the two types of cells to bathe in the same fluid without coming into physical contact, retinal neurons in a bath with hUTCs formed new connections between neurons called synapses, and they sprouted new ‘neurites’ — tiny branches that lead to additional connections.
These cells also survived longer than rat neurons placed in a bath lacking the umbilical cord tissue-derived cells.
Something present in the fluid surrounding the neurons in the bath with the hUTCs was apparently affecting the neurons. Through a series of experiments, the researchers determined that relatively large molecules, thrombospondin 1, 2 and 4, were primarily responsible for the effect.
Blocking thrombospondins was found to reduce new connections among neurons. By genetically inhibiting the individual members of the thrombospondin family, the researchers found that TSP1, TSP2, and TSP4 in particular were required to create both neurites and new connections.
“It’s exciting that thrombospondins had a really strong effect on neurite outgrowth,” said Eroglu, who is also a member of the Duke Institute for Brain Sciences (DIBS). She added that making neurites and forming new connections between them are crucial for helping neurons grow when faced with injury and neurodegenerative diseases.
However, blocking TSP1, 2 and 4 did not affect neuron survival, suggesting that there is some other factor in the UTC cells that promotes cell longevity. Her group is now searching for those molecules.
Eroglu’s earlier work has shown that thrombospondins are released by brain cells called astrocytes and boost new synapse formation between neurons in the brain.
Eroglu said there may be deficiencies in thrombospondin signaling in neurodegenerative disease, and the group is actively pursuing this hypothesis in animal studies.
Postdoctoral fellow Sehwon Koh is the lead author of this study and a member of the Eroglu lab. Other authors include Namsoo Kim and Henry H. Yin from Duke’s department of psychology and neuroscience. This research was supported by a research agreement with Janssen Research & Development, LLC.
CITATION: “Human Umbilical Tissue-Derived Cells (hUTC) Promote Synapse Formation and Neurite Outgrowth via Thrombospondin Family Proteins,” Sehwon Koh, Namsoo Kim, Henry H. Yin, Ian R. Harris, Nadine S. Dejneka, and Cagla Eroglu. Journal of Neuroscience, November 25, 2015.    http://dx.doi.org:/10.1523/JNEUROSCI.1364-15.2015
ScienceDaily
Cells isolated from the human umbilical cord have been shown to produce molecules that help retinal neurons from the eyes of rats grow, connect and survive. The findings implicate one family of molecules in particular — thrombospondins – that may have therapeutic potential for the treatment of degenerative eye diseases.

The findings, which appear Nov. 25 in the Journal of Neuroscience, implicate one family of molecules in particular — thrombospondins — that may have therapeutic potential for the treatment of degenerative eye diseases.

“By learning more about how these cells work, we are one step closer to understanding the disease states in which these cells should be studied,” said Cagla Eroglu, an assistant professor of cell biology and neurobiology at the Duke University Medical Center, who led the research.

Umbilical cord tissue-derived cells (hUTC) differ from umbilical cord blood cells in that they are isolated from cord tissue itself, rather than the blood. The Duke team used an established cell culture system to determine whether and how the hUTCs might affect the growth of neurons isolated from the retinas of rat eyes.

Something present in the fluid surrounding the neurons in the bath with the hUTCs was apparently affecting the neurons. Through a series of experiments, the researchers determined that relatively large molecules, thrombospondin 1, 2 and 4, were primarily responsible for the effect.

Blocking thrombospondins was found to reduce new connections among neurons. By genetically inhibiting the individual members of the thrombospondin family, the researchers found that TSP1, TSP2, and TSP4 in particular were required to create both neurites and new connections.

However, blocking TSP1, 2 and 4 did not affect neuron survival, suggesting that there is some other factor in the UTC cells that promotes cell longevity. Her group is now searching for those molecules.

Golgi Cells Have Active Dendrites
Stephanie Rudolph, Court Hull, and Wade G. Regehr
The Journal of Neuroscience, Nov 25, 2015 • 35(47):i • i    (see pages 15492–15504)
The cerebellum coordinates multijoint movements and contributes to motor learning. These functions require precise spike timing in Purkinje cells, the cerebellar output neurons. Purkinje cell spiking is driven partly by granule cells, which receive information about ongoing movements from mossy fibers, and the timing and spatial extent of granule cell output is determined largely by inhibitory input from spontaneously active interneurons called Golgi cells.
Golgi cell spiking is modulated by excitatory input from both mossy fibers and granule cells. How these inputs are integrated in Golgi cell dendrites remains poorly understood. Finding no evidence for active conductances in Golgi cell dendrites, Vervaeke et al. (2012, Science 30: 1624) hypothesized that dendritic gap junctions enable granule cell inputs to influence Golgi cell activity. Although gap junctions likely do contribute to dendritic processing in Golgi cells, Rudolph et al. now show that Golgi cell dendrites also express voltage-gated channels.
If dendrites lacked active conductances, one would expect signals to decay with distance from the soma. But calcium imaging in rat cerebellar slices revealed that action potentials caused uniform calcium elevation throughout Golgi cell dendrites. Moreover, applying a voltage-gated sodium channel (VGSC) blocker selectively to dendrites reduced spike-associated calcium elevation in distal dendrites. In addition, blocking T- and R-type voltage-gated calcium channels (VGCCs) attenuated calcium elevation selectivelyin distal dendrites,while blocking N-type channels reduced calcium elevation only in proximal dendrites.
Blocking voltage-gated channels also had functional consequences. Blocking N-type channels decreased the amplitude of the spike afterhyperpolarization and increased the spike rate of Golgi cells. In contrast, T-type channel blockers had little effect on baseline firing frequency. Nonetheless, blocking T-type channels attenuated rebound spiking after hyperpolarization and reduced the amplitude of EPSPs evoked by stimulation of granule cell axons.
These experiments suggest that VGSCs help depolarize distal dendrites to enhance activation of T-type VGCCs, which in turn amplify responses to granule cells and promote rebound bursting. Meanwhile, N-type VGCCs located near the soma appear to be tightly coupled to calcium-activated potassium channels, which regulate the spontaneous spike rate of Golgi cells. Thus, Golgi cell dendrites have multiple types of voltage-sensitive channels that are differently distributed and serve distinct roles in ensuring the precise timing of cerebellar output.
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