{"id":13912,"date":"2015-05-29T08:51:31","date_gmt":"2015-05-29T08:51:31","guid":{"rendered":"http:\/\/healthmedicinet.com\/news\/researchers-unravel-a-genetic-link-with-autistic-behaviors-and-find-a-way-to-undo-it\/"},"modified":"2015-05-29T08:51:31","modified_gmt":"2015-05-29T08:51:31","slug":"researchers-unravel-a-genetic-link-with-autistic-behaviors-and-find-a-way-to-undo-it","status":"publish","type":"post","link":"http:\/\/healthmedicinet.com\/news\/researchers-unravel-a-genetic-link-with-autistic-behaviors-and-find-a-way-to-undo-it\/","title":{"rendered":"Researchers unravel a genetic link with autistic behaviors \u00e2\u20ac\u201d and find a way to undo it"},"content":{"rendered":"

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IMAGE:\u00c2\u00a0<\/strong>New research by Dr. Yan and her co-authors describes the cellular and molecular basis behind some autistic behaviors and suggests potential biomarkers and pharmaceutical targets.
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Credit: School of Medicine and Biomedical Sciences, University at Buffalo<\/p>\n<\/p>\n<\/figcaption>\n<\/figure>\n

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BUFFALO, N.Y. \u00e2\u20ac\u201d Scientists at the University at Buffalo have identified the mechanisms behind a genetic mutation that produces certain autistic behaviors in mice, as well as therapeutic strategies to restore normal behaviors.\n<\/p>\n

The research describes the cellular and molecular basis behind some autistic behaviors; it also suggests potential biomarkers and pharmaceutical targets.\n<\/p>\n

Published May 28 in Cell Reports<\/em>, the research was led by Zhen Yan, PhD, professor in the Department of Physiology and Biophysics in the UB School of Medicine and Biomedical Sciences.\n<\/p>\n

The paper focuses on the loss of a gene called Shank3, an important risk factor for autism spectrum disorders (ASD). The researchers trace how this risk factor disrupts communication between neurons, leading to social deficits in mice. And, in their most important finding, they are able to reverse these neuronal disruptions, restoring normal behavior in mice.\n<\/p>\n

Previous studies have shown that approximately 84 percent of people with a Shank3 deletion or loss-of-function mutation had an ASD. But just how this occurs has remained unknown.\n<\/p>\n

The paper states that mice with a Shank3 deficiency exhibited \u00e2\u20ac\u0153drastically reduced\u00e2\u20ac\u009d interest in social stimuli, i.e., other mice, versus inanimate objects, suggesting \u00e2\u20ac\u0153severe social deficits.\u00e2\u20ac\u009d They also spent significantly more time in repetitive self-grooming than normal mice.\n<\/p>\n

The UB researchers found that the Shank3 deficiency plays a key role in how neurons communicate. It has a significant effect on the activation of the NMDA (n-methyl-D-aspartate) receptor, which is critical to learning and memory.\n<\/p>\n

Yan explained that the Shank3 deficiency disrupts the trafficking of this receptor and its function at critical transmission sites in the brain. That disruption, they found, results from the dysregulation of actin filaments, which act as a kind of cellular \u00e2\u20ac\u0153highway\u00e2\u20ac\u009d in the brain\u00e2\u20ac\u2122s prefrontal cortex, the command center for \u00e2\u20ac\u0153high-level\u00e2\u20ac\u009d executive functions and a key region implicated in ASD.\n<\/p>\n

\u00e2\u20ac\u0153This research is the first to show that, in animals, abnormal actin regulation causes autism-like behaviors,\u00e2\u20ac\u009d said Yan.\n<\/p>\n

\u00e2\u20ac\u0153Actin filaments are very dynamic structures that are constantly being assembled and disassembled, processes controlled by numerous regulators,\u00e2\u20ac\u009d Yan explained.\n<\/p>\n

When something upsets the equilibrium of actin filament assembly, key cellular functions fall apart.\n<\/p>\n

\u00e2\u20ac\u0153With Shank3 deficiency, we have found that the expression or activity of some actin regulators, such as cofilin, is altered,\u00e2\u20ac\u009d explained Yan. \u00e2\u20ac\u0153This upsets the equilibrium of actin filament assembly, which, in turn, disrupts the normal delivery and maintenance of NMDA and other critical receptors.\u00e2\u20ac\u009d\n<\/p>\n

The result is a very significant effect on the functional plasticity of the synapse, which, in turn, leads to the manifestation of some autistic behaviors.\n<\/p>\n

In its most dramatic finding, the researchers found they were able to reverse this process, restoring normal behaviors in the Shank3-deficient mice, once the activity of cofilin or other regulators was returned to normal. This, in turn, restored actin dynamics at cortical synapses, allowing for the normal trafficking and functioning of NMDA receptors.\n<\/p>\n

\u00e2\u20ac\u0153Once actin filaments and NMDA receptors returned to normal, we observed a robust and long-lasting rescue of the social interaction deficits and repetitive behavior in the Shank3-deficient mice,\u00e2\u20ac\u009d said Yan. \u00e2\u20ac\u0153Our results suggest a promising therapeutic strategy for treating autism.\u00e2\u20ac\u009d<\/p>\n

The researchers are seeking funding to continue their work developing potential biomarkers and treatments for autism.\n<\/p>\n

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Yan\u00e2\u20ac\u2122s co-authors are Lara Duffney, PhD, former doctoral student; Ping Zhong, PhD, research assistant professor; Jing Wei, PhD, research assistant professor, Emmanuel Matas, PhD, postdoctoral associate; Jia Cheng, PhD, former doctoral student; Luye Qin, research scientist and Kaijie Ma, research assistant, all in the UB Department of Physiology and Biophysics; also, David Dietz, PhD, assistant professor in the UB Department of Pharmacology and Toxicology; and Yuji Kajiwara and Joseph D. Buxbaum of the Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai.\n<\/p>\n

Founded in 1846, the University at Buffalo School of Medicine and Biomedical Sciences is beginning a new chapter in its history with the largest medical education building under construction in the nation. The eight-story, 628,000-square-foot facility is scheduled to open in 2017. The new location puts superior medical education, clinical care and pioneering research in close proximity, anchoring Buffalo\u00e2\u20ac\u2122s evolving comprehensive academic health center in a vibrant downtown setting. These new facilities will better enable the school to advance health and wellness across the life span for the people of New York and the world through research, clinical care and the education of tomorrow\u00e2\u20ac\u2122s leaders in health care and biomedical sciences. The school\u00e2\u20ac\u2122s faculty and residents provide care for the community\u00e2\u20ac\u2122s diverse populations through strong clinical partnerships and the school\u00e2\u20ac\u2122s practice plan, UBMD.<\/p>\n","protected":false},"excerpt":{"rendered":"

IMAGE:\u00c2\u00a0New research by Dr. Yan and her co-authors describes the cellular and molecular basis behind some autistic behaviors and suggests potential biomarkers and pharmaceutical targets. view more Credit: School of Medicine and Biomedical Sciences, University at Buffalo BUFFALO, N.Y. \u00e2\u20ac\u201d Scientists at the University at Buffalo have identified the mechanisms behind a genetic mutation that […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[],"tags":[],"class_list":["post-13912","post","type-post","status-publish","format-standard","hentry"],"_links":{"self":[{"href":"http:\/\/healthmedicinet.com\/news\/wp-json\/wp\/v2\/posts\/13912","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/healthmedicinet.com\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/healthmedicinet.com\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/healthmedicinet.com\/news\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/healthmedicinet.com\/news\/wp-json\/wp\/v2\/comments?post=13912"}],"version-history":[{"count":0,"href":"http:\/\/healthmedicinet.com\/news\/wp-json\/wp\/v2\/posts\/13912\/revisions"}],"wp:attachment":[{"href":"http:\/\/healthmedicinet.com\/news\/wp-json\/wp\/v2\/media?parent=13912"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/healthmedicinet.com\/news\/wp-json\/wp\/v2\/categories?post=13912"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/healthmedicinet.com\/news\/wp-json\/wp\/v2\/tags?post=13912"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}