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Interactions with Astroglia Influence the Shape of the Developing Dendritic Arbor and Restrict Dendrite Growth Independent of Promoting Synaptic Contacts

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  • Ref Interactions with Astroglia Influence the Shape of the Developing Dendritic Arbor and Restrict Dendrite Growth Independent of Promoting Synaptic Contacts

    http://journals.plos.org/plosone/art...s-1701-neuroup

    Abstract

    Astroglia play key roles in the development of neurons, ranging from regulating neuron survival to promoting synapse formation, yet basic questions remain about whether astrocytes might be involved in forming the dendritic arbor. Here, we used cultured hippocampal neurons as a simple in vitro model that allowed dendritic growth and geometry to be analyzed quantitatively under conditions where the extent of interactions between neurons and astrocytes varied. When astroglia were proximal to neurons, dendrites and dendritic filopodia oriented toward them, but the general presence of astroglia significantly reduced overall dendrite growth. Further, dendritic arbors in partial physical contact with astroglia developed a pronounced pattern of asymmetrical growth, because the dendrites in direct contact were significantly smaller than the portion of the arbor not in contact. Notably, thrombospondin, the astroglial factor shown previously to promote synapse formation, did not inhibit dendritic growth. Thus, while astroglia promoted the formation of presynaptic contacts onto dendrites, dendritic growth was constrained locally within a developing arbor at sites where dendrites contacted astroglia. Taken together, these observations reveal influences on spatial orientation of growth as well as influences on morphogenesis of the dendritic arbor that have not been previously identified.




    Not All Astrocytes in the Brain Are the Same

    http://neurosciencenews.com/astrocyt...oscience-7084/

    UCLA researchers upend long-standing idea that the star-shaped brain cells can’t be differentiated from each other.

    From afar, the billions of stars in our galaxy look indistinguishable, just as the billions of star-shaped astrocytes in our brains appear the same as each other. But UCLA researchers have now revealed that astrocytes, a type of brain cell that supports and protects neurons, aren’t all the same. While stars might be categorized by their size, age and heat, the supportive brain cells vary when it comes to shape, molecular machinery and functioning.

    The findings, published today in the journal Neuron, should make it easier for researchers to study how astrocytes relate to disease, or to develop drugs that aim to target small subsets of astrocytes, said Baljit Khakh, a UCLA professor of physiology and neurobiology and the study’s senior author.

    “For 50 years, the textbooks have said that astrocytes everywhere in the brain are largely identical,” Khakh said. “We’ve now discovered that astrocytes in different circuits in the brain are different, and we’ve developed a comprehensive toolkit to explore astrocyte biology and diversity.”

    Unlike neurons, astrocytes in the brain don’t directly process information, store memories or control the body’s movements. Instead, astrocytes — which have been described as glue-like — are known to compose the blood-brain barrier, give the brain structure, carry nutrients to neurons, and regulate the concentration of certain molecules between neurons. They also play a key role in helping the brain repair itself after traumatic injuries, strokes or infections. And studies have suggested links between impaired astrocytes and diseases of the nervous system, including Huntington’s, ALS, multiple sclerosis and Alzheimer’s.
    “Essentially all brain diseases likely contain an astrocytic component,” Khakh said. “But it hasn’t been explored much because there just haven’t been good enough methods to study the astrocytes.”

    To test the long-held theory that astrocytes throughout the brain have the same properties and functions, Khakh and his colleagues looked at astrocytes in two areas of mouse brains. The two areas — the dorsolateral striatum and the hippocampus CA1 stratum radiatum — are known to be quite different in their functions and the types of neurons they contain. The dorsolateral striatum is involved in controlling movement, while the hippocampus helps establish long-term memories. The scientists performed dozens of in-depth tests on the astrocytes from each area of the brain.

    Khakh’s team found that the astrocytes in the striatum and hippocampus had differences that affected how they functioned and how they interacted with neurons. The cells varied between the two brain circuits when it came to how they interacted with neurons and conducted chemicals across their membranes. Moreover, the astrocytes in the striatum had different genes turned on than astrocytes from the hippocampus.


    In the past, most researchers dismissed the idea that drugs could selectively target small sets of astrocytes to try to treat brain diseases, because of the assumption that a drug targeting astrocytes would impact the whole brain. “But we’re seeing differences between astrocytes in different areas, and I suspect there are differences far greater than what we’ve seen so far,” Khakh said. The new observation means that it may be possible for drugs to work on just a small subset of astrocytes, selected by their molecular characteristics.

    “Deepening our understanding of astrocyte biology in the healthy brain enables us to examine what happens to these cells in neuropsychiatric disorders and potentially intervene in astrocytes in a specific brain region for therapeutic benefit,” said Hua Chai, a UCLA graduate student and co-first author of the new paper.

    “Our work suggests that differences in astrocyte functions between circuits may be one of the main reasons why in some neurological diseases, there are brain regions that are more susceptible than others,” added Blanca Diaz-Castro, a postdoctoral research fellow in the Khakh lab and co-first author of the paper.

    The team has further questions about the astrocytes in the striatum and hippocampus and plans to start analyzing astrocytes from other areas of the brain.
    Update 16/07/2017
    Last edited by Jo Bowyer; 16-07-2017, 01:54 PM.
    Jo Bowyer
    Chartered Physiotherapist Registered Osteopath.
    "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

  • #2
    Astrocytes Play Key Role in Respiratory Center and Breathing Regulation

    http://neurosciencenews.com/astrocyt...y-center-7666/
    Jo Bowyer
    Chartered Physiotherapist Registered Osteopath.
    "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

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