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        Chronic stress and

        depression boost this

        brain receptor; a new study

        maps out how to block it

              cientists reveal the structure   In the study, published Nov. 18 in   estimated to affect roughly 20
              of GPR158, a factor involved   the journal Science, the researchers   million people in the United
        Sin major depression,                used ultracold, single-particle     States in any given year. Current
        presenting a much-needed             electron microscopy, or cryo-EM, to   treatments work on other known
        alternative approach to helping      map, at a resolution of about a third   receptors, including monoamine,
        people with mood disorders           of a billionth of a meter, the atomic   but don’t always work well for all
                                             structure of GPR158, both on its    people and alternative options
        Scientists at Scripps Research,      own and when bound to a group of    are needed.
        Florida have determined the          proteins that mediate its activity.
        near-atomic-scale structure of                                           Martemyanov and his team found
        an unusual brain-cell receptor       “We’ve been studying this receptor   in a 2018 study that GPR158 is
        called GPR158, which has been        for more than 10 years, and have    present at unusually high levels
        linked to depression and anxiety.    done a lot of biology on it, so it’s   in the prefrontal cortex of people
        The structural study reveals both    really gratifying to see for the first   diagnosed with major depressive
        the receptor and its regulating      time how it’s organized,” says      disorder at the time of their death.
        complex, advancing understanding     lead author Kirill Martemyanov,     They also found that exposing mice
        of basic cell receptor biology. It   PhD, Professor and Chair of the     to chronic stress increased levels of
        also enables work on potential       Department of Neuroscience at the   this receptor in the mouse prefrontal
        therapeutics designed to block       Scripps Research.                   cortex, leading to depression-like
        GPR158 as a strategy for treating
        depression, anxiety and possibly     Clinical depression, also called                              8
        other mood disorders.                major depressive disorder, is

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