• Atlas of migraine cell types sheds light

    From ScienceDaily@1:317/3 to All on Monday, March 28, 2022 22:30:40
    Atlas of migraine cell types sheds light on new therapeutic targets


    Date:
    March 28, 2022
    Source:
    Brigham and Women's Hospital
    Summary:
    By mapping the cell types and genes expressed in the human and mouse
    trigeminal ganglion, researchers have created an online resource
    for studying the molecular basis of headache and facial pain.



    FULL STORY ========================================================================== Headaches such as migraine are among the leading causes of morbidity
    worldwide, but most treatments provide only partial relief. While
    scientists know that migraine and related headaches are caused by activity
    in a part of the nervous system known as the trigeminal ganglion (TG),
    it remains unclear which genes and cell types of the TG are involved. By analyzing both human and mouse TG, investigators from Brigham and Women's Hospital and Massachusetts General Hospital profiled, at single-cell resolution, the genes expressed in each TG cell type. Their research,
    published in Neuron, will allow researchers to design more effective
    treatments for pain by selectively targeting certain genes and cells.


    ========================================================================== "Very few pain therapeutics have made it to the clinic, despite strong
    efficacy in animal models, so our goal was to analyze human tissue to
    look for new targets for headache and facial pain treatment," said William Renthal, MD, PhD, of the Department of Neurology at the Brigham. "We now
    have an atlas of the genes that are expressed in each of the cell types
    in the TG, the key relay center for migraine and facial pain, and we
    are now using this tool to identify potential therapeutic targets that
    are selectively expressed in cell types that drive head pain. We believe
    this will lead to more precise medicines without as many side effects."
    In addition to analyzing the TG of four human donors, the researchers
    studied two mouse models of headache. Importantly, they found that while
    cell types between mice and human are largely conserved, some of the
    genes known to be involved in pain are expressed in different subsets of
    cells in mice versus humans. This gave the researchers new ideas about
    which cells to study further.

    "A major value of this study is that it wasn't limited to one specific
    cell- type or branch of the trigeminal ganglion," said Jochen K. Lennerz,
    MD, PhD, of the Center for Integrated Diagnostics in the Department of Pathology at MGH.

    Lennerz's lab performed the complex tissue-harvesting procedures
    required to extract the TG, which is located inside the cranium but has
    neurons that enervate the teeth, eyes, and other facial structures. "We included all of the cells that make up the TG," he said. "This was a
    very holistic approach which has resulted in an amazing compendium that researchers can look at from all perspectives and specialties. It may
    not only be neurons we are looking for when identifying biomolecules
    as therapeutic targets." The information from the researchers' atlas,
    which is available publicly online, could prompt new investigations
    into the molecular basis of different varieties of pain, such as tooth
    pain. It may also shed light on how to treat head pain beyond migraine, including post-concussive headaches or cluster headaches.

    Going forward, the researchers plan to improve the current atlas by
    sequencing additional human tissues. They hope that the atlas can help researchers develop more selective pain therapeutics by targeting,
    through gene therapies, the specific cells they've identified.

    "We have a resource now that allows an individual to go online, look
    up a gene of interest, find out where it's expressed and how it's
    regulated, and then use this information to inspire new experiments,"
    Renthal said. "This atlas is only a first draft, and we need to expand
    the number of donors to build a more complete one. That's a current
    limitation but also a future direction for our work." Disclosures:
    Renthal receives research funding from Teva Pharmaceuticals and is on
    an AbbVie scientific advisory board.

    Funding: Funding for this work was primarily provided by the Migraine
    Research Foundation and the Burroughs Wellcome Fund. Researchers are
    also supported by the National Institute of Neurological Disorders and
    Stroke (K08NS101064, R01NS119476, R01NS115972 and R01NS078263), National Institute of Drug Abuse (DP1DA054343), Teva Pharmaceuticals, Brigham
    and Women's Hospital Women's Brain Initiative and Neurotechnology studio.


    ========================================================================== Story Source: Materials provided by Brigham_and_Women's_Hospital. Note:
    Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Lite Yang, Mengyi Xu, Shamsuddin A. Bhuiyan, Jia Li, Jun Zhao,
    Randall J.

    Cohrs, Justin T. Susterich, Sylvia Signorelli, Ursula Green,
    James R.

    Stone, Dan Levy, Jochen K. Lennerz, William Renthal. Human and
    mouse trigeminal ganglia cell atlas implicates multiple cell types
    in migraine.

    Neuron, 2022; DOI: 10.1016/j.neuron.2022.03.003 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220328112105.htm

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