{"id":2557,"date":"2015-08-11T00:00:00","date_gmt":"2015-08-11T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/receptors-in-brain-linked-to-schizophrenia-autism\/"},"modified":"2017-08-18T16:25:08","modified_gmt":"2017-08-18T23:25:08","slug":"receptors-in-brain-linked-to-schizophrenia-autism","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/receptors-in-brain-linked-to-schizophrenia-autism\/","title":{"rendered":"Receptors in brain linked to schizophrenia, autism"},"content":{"rendered":"<p>\nLA JOLLA\u2013The loss of a critical receptor in a special class of inhibitory neurons in the<br \/>\nbrain may be responsible for neurodevelopmental disorders including autism and schizophrenia, according to new research by Salk scientists.\n<\/p>\n<p>\nThe importance of the receptor, called mGluR5, in other areas of the brain had been previously established. Until now, however, no one had studied their specific role in a cell type known as parvalbumin-positive interneurons, thought to be important in general cognition and generating certain types of oscillatory wave patterns in the brain.\n<\/p>\n<p>\n\u201cWe found that without this receptor in the parvalbumin cells, mice have many serious behavioral deficits,\u201d says <a href=\"https:\/\/www.salk.edu\/zh\/faculty\/sejnowski.html\/\">\u7279\u4f26\u65af\u00b7\u585e\u6d25\u8bfa\u7ef4\u5947<\/a>, head of Salk\u2019s <a href=\"http:\/\/cnl.salk.edu\/\">\u8ba1\u7b97\u795e\u7ecf\u751f\u7269\u5b66\u5b9e\u9a8c\u5ba4<\/a>, which led the research published in <em><a href=\"http:\/\/dx.doi.org\/10.1038\/MP.2015.113\">Molecular Psychiatry<\/a><\/em> on August 11, 2015. \u201cAnd a lot of them really mimic closely what we see in schizophrenia.\u201d\n<\/p>\n<div class=\"imageCaption530\"><img decoding=\"async\" alt=\"\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/01\/2104-Sejnowski-Fig.jpg\"><\/p>\n<p>When mice are engineered to lack the mGluR5 receptor in parvalbumin cells (right), they have fewer inhibitory (red) connections controlling the activity of excitatory neurons.<\/p>\n<p><a target=\"_blank\" href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/02\/2104-Sejnowski-Fig.jpg\">Click here<\/a> for a high-resolution image.<\/p>\n<p>\nImage: Courtesy of the Salk Institute for Biological Studies\n<\/p>\n<\/div>\n<p>\nScientists had previously discovered that when molecular signaling was disrupted in these cells during development, the brain\u2019s networks didn\u2019t form correctly. Separate studies have revealed that mGluR5 receptors, which transmit glutamate signaling in the brain, are linked to addiction disorders, anxiety and Fragile X Syndrome. But, in these cases, mGluR5 is affected in excitatory cells, not inhibitory cells like the parvalbumin-positive interneurons.\n<\/p>\n<p>\nThe Salk team wondered what the role of mGluR5 was in the parvalbumin cells since the cells were deemed so important in brain development. They partnered with Athina Markou\u2019s team from the Department of Psychiatry at the University of California, San Diego, to examine what happened when the receptor was selectively deleted from these cells after the brain\u2019s initial formation. Without the receptor in these cells, they found, mice had a host of developmental problems, including obsessive, repetitive grooming behavior and anti-social tendencies. Moreover, the patterns of activity in the animals\u2019 brains resembled those seen in humans suffering from schizophrenia.\n<\/p>\n<p>\n\u201cThis discovery implies that changes after birth, not just before birth, are affecting the way the network is set up,\u201d says <a href=\"https:\/\/www.salk.edu\/zh\/scientist\/margaritabehrens\/\">Margarita Behrens<\/a>, corresponding author and Salk staff scientist.\n<\/p>\n<p>\nThe results suggest that an alteration in mGluR5 receptors in these brain cells may be a critical step in the formation of some neurodevelopmental disorders, adds Sejnowski. It\u2019s good news, he says, because the molecular change is potentially reversible.\n<\/p>\n<div class=\"imageCaption530\"><img decoding=\"async\" alt=\"\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/01\/2104-Terry-Sejnowski-and-Maria-Margarita-Behrens.jpg\"><\/p>\n<p>\nTerrence Sejnowski and Margarita Behrens<\/p>\n<p><a target=\"_blank\" href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/02\/2104-Terry-Sejnowski-and-Maria-Margarita-Behrens.jpg\">Click here<\/a> for a high-resolution image.<\/p>\n<p>\nImage: Courtesy of the Salk Institute for Biological Studies\n<\/p>\n<\/div>\n<p>\n\u201cThe cells are still alive, and if we can figure out how to go in and change some of these molecular switches, we might actually be able to put the cells back into healthy, functioning states,\u201d he says.\n<\/p>\n<p>\nBehrens says the study also should be a signal of caution to the pharmaceutical industry to be wary of drugs that affect mGluR5 throughout the whole brain. \u201cThere are a lot of clinical trials ongoing looking at modulating mGluR5 for anxiety and Fragile X Syndrome,\u201d she says. \u201cBut our results suggest that if you affect parvalbumin neurons, you might get behavioral changes you weren\u2019t expecting.\u201d\n<\/p>\n<p>\nMore research is needed to show whether the parvalbumin cells\u2019 mGluR5 receptors are linked to disease in humans and, if so, what causes the loss or disruption to the receptors.\n<\/p>\n<p>\nOther researchers on the study were A. Pinto-Duarte, A. Kappe, A. Zembrzycki, E.A. Mukamel, K. Lucero, and X. Wang of the Salk Institute; and S.A. Barnes and A. Markou of the University of California, San Diego.\n<\/p>\n<p>\nThe work and the researchers involved were supported by grants from the National Institutes of Health and Howard Hughes Medical Institute, and a Calouste Gulbenkian Foundation Fellowship.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[114],"disease-research":[169,124,167],"class_list":["post-2557","disclosure","type-disclosure","status-publish","hentry","faculty-terrence-sejnowski","disease-research-autism","disease-research-neuroscience-and-neurological-disorders","disease-research-schizophrenia"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Receptors in brain linked to schizophrenia, autism - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/receptors-in-brain-linked-to-schizophrenia-autism\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Receptors in brain linked to schizophrenia, autism - 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