{"id":128329,"date":"2024-11-21T07:31:40","date_gmt":"2024-11-21T00:31:40","guid":{"rendered":"https:\/\/hotvideos24.online\/?p=128329"},"modified":"2024-11-21T07:31:40","modified_gmt":"2024-11-21T00:31:40","slug":"gene-repair-restores-brain-signal-efficiency-in-autism","status":"publish","type":"post","link":"https:\/\/hotvideos24.online\/?p=128329","title":{"rendered":"Gene Repair Restores Brain Signal Efficiency in Autism"},"content":{"rendered":"<p> <script async src=\"https:\/\/pagead2.googlesyndication.com\/pagead\/js\/adsbygoogle.js?client=ca-pub-3711241968723425\"\r\n     crossorigin=\"anonymous\"><\/script>\r\n<ins class=\"adsbygoogle\"\r\n     style=\"display:block\"\r\n     data-ad-format=\"fluid\"\r\n     data-ad-layout-key=\"-fb+5w+4e-db+86\"\r\n     data-ad-client=\"ca-pub-3711241968723425\"\r\n     data-ad-slot=\"7910942971\"><\/ins>\r\n<script>\r\n     (adsbygoogle = window.adsbygoogle || []).push({});\r\n<\/script><br \/>\n<\/p>\n<div>\n<p><strong>Summary: <\/strong>Autism-linked SHANK3 gene mutations disrupt not only neurons but also oligodendrocytes, essential for producing myelin, which insulates nerve fibers. This damage reduces brain signal efficiency and impairs behavior.<\/p>\n<p>Using gene therapy, researchers successfully repaired these cells in a mouse model, restoring their function and myelin production. They validated their findings with human-derived stem cells, confirming similar impairments and repair mechanisms.<\/p>\n<p>This discovery highlights a significant role for oligodendrocytes in autism and opens the door for innovative treatments targeting myelin dysfunction. The study underscores both the biological complexity of autism and the promise of genetic therapies for intervention.<\/p>\n<p><strong>Key Facts:<\/strong><\/p>\n<ul class=\"wp-block-list\">\n<li>SHANK3 mutations impair myelin production, disrupting neural signal efficiency.<\/li>\n<li>Gene therapy restored proper function in oligodendrocytes in mice and human cells.<\/li>\n<li>Findings highlight oligodendrocytes\u2019 critical role beyond neuronal support in autism.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>Tel Aviv University<\/p>\n<p><strong>A groundbreaking study from Tel Aviv University expands the understanding of the biological mechanism underlying genetically-based autism, specifically mutations in the\u00a0<em>SHANK3<\/em>\u00a0gene, responsible for nearly one million cases of autism worldwide. <\/strong><\/p>\n<p>Based on these discoveries, the research team applied a genetic treatment that improved the function of cells affected by the mutation, laying a foundation for future treatments for\u00a0<em>SHANK3<\/em>-related autism.<\/p>\n<figure class=\"wp-block-image size-full\"><picture fetchpriority=\"high\" decoding=\"async\" class=\"wp-image-106370\"><source type=\"image\/webp\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience.jpg.webp 1200w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-300x200.jpg.webp 300w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-770x513.jpg.webp 770w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-1155x770.jpg.webp 1155w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-370x247.jpg.webp 370w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-293x195.jpg.webp 293w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-150x100.jpg.webp 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/><img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"800\" src=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience.jpg\" alt=\"This shows a brain.\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience.jpg 1200w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-300x200.jpg 300w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-770x513.jpg 770w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-1155x770.jpg 1155w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-370x247.jpg 370w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-293x195.jpg 293w, https:\/\/neurosciencenews.com\/files\/2024\/11\/autism-gene-therapy-myelin-neuroscience-150x100.jpg 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/> <\/picture><figcaption class=\"wp-element-caption\">When the myelin is faulty, the electrical signals transmitted through the axons may leak, disrupting the message transmission between brain regions and impairing brain function. Credit: Neuroscience News<\/figcaption><\/figure>\n<p>The study was led by the lab of Prof. Boaz Barak and PhD student Inbar Fischer from the Sagol School of Neuroscience and the School of Psychological Sciences at Tel Aviv University, in collaboration with the labs of Prof. Ben Maoz from the Department of Biomedical Engineering at Fleischman Faculty of Engineering at Tel Aviv University and Prof. Shani Stern from the Department of Neurobiology at the University of Haifa.<\/p>\n<p>The article was published in the prestigious journal\u00a0<em>Science Advances<\/em>.<\/p>\n<p>Prof. Barak: \u201cAutism is a relatively common neurodevelopmental disorder. According to current data, 1-2% of the global population and one in every 36 boys in the U.S. are diagnosed with autism spectrum disorder (ASD), with numbers rising over time.<\/p>\n<p>\u201cAutism is caused by a wide range of factors \u2013 environmental, genetic, and even social and cultural (such as the rise in parental age at conception).<\/p>\n<p>\u201cIn my lab, we study genetic causes of autism. Among these, mutations in a gene called\u00a0<em>SHANK3<\/em>.<\/p>\n<p>\u201cThe impact of these mutations on the function of brain neurons has been extensively studied, and we know that the protein encoded by\u00a0<em>SHANK3<\/em>\u00a0plays a central role in binding receptors in the neuron, essential for receiving chemical signals (neurotransmitters and others) by which neurons communicate.<\/p>\n<p>\u201cThus, damage to this gene can disrupt message transmission between neurons, impairing the brain\u2019s development and function.<\/p>\n<p>\u201cIn this study we sought to shed light on other, previously unknown mechanisms, through which mutations in the\u00a0<em>SHANK3<\/em>\u00a0gene disrupt brain development, leading to disorders manifested as autism.\u201d<\/p>\n<p>Specifically, the research team focused on two components in the brain not yet studied extensively in this context: non-neuronal brain cells (glia) called oligodendrocytes and the myelin they produce.<\/p>\n<p>Myelin tissue is a fatty layer that insulates nerve fibers (axons), similar to the insulating layer that coats electrical cables. When the myelin is faulty, the electrical signals transmitted through the axons may leak, disrupting the message transmission between brain regions and impairing brain function.<\/p>\n<p>The team employed a genetically engineered mouse model for autism, introducing a mutation in the\u00a0<em>Shank3<\/em>\u00a0gene that mirrors the mutation found in humans with this form of autism.<\/p>\n<p>Inbar Fischer: \u201cThrough this model, we found that the mutation causes a dual impairment in the brain\u2019s development and proper function: first, in oligodendrocytes, as in neurons, the SHANK3 protein is essential for the binding and functioning of receptors that receive chemical signals (neurotransmitters and others) from neighboring cells.<\/p>\n<p>\u201cThis means that the defective protein associated with autism disrupts message transmission to these vital support cells. Secondly, when the function and development of oligodendrocytes is impaired, their myelin production is also disrupted.<\/p>\n<p>\u201cThe faulty myelin does not properly insulate the neuron\u2019s axons, thereby reducing the efficiency of electrical signal transmission between brain cells, as well as the synchronization of electrical activity between different parts of the brain.<\/p>\n<p>\u201cIn our model, we found myelin impairment in multiple brain areas and observed that the animals\u2019 behavior was adversely affected as a result.\u201d<\/p>\n<p>The researchers then sought a method for fixing the damage caused by the mutation, with the hope of ultimately developing a treatment for humans.<\/p>\n<p>Inbar Fischer: \u201cWe obtained oligodendrocytes from the brain of a mouse with a\u00a0<em>Shank3<\/em>\u00a0mutation, and inserted DNA segments containing the normal human\u00a0<em>SHANK3<\/em>\u00a0sequence.<\/p>\n<p>\u201cOur goal was to allow the normal gene to encode a functional and normal protein, which, replacing the defective protein, would perform its essential role in the cell. To our delight, following treatment, the cells expressed the normal SHANK3 protein, enabling the construction of a functional protein substrate to bind the receptors that receive electrical signals.<\/p>\n<p>\u201cIn other words, the genetic treatment we had developed repaired the oligodendrocytes\u2019 communication sites, essential for the cells\u2019 proper development and function as myelin producers.\u201d<\/p>\n<p>To validate findings from the mouse model, the research team generated induced pluripotent stem cells from skin cells of a girl with autism caused by a<em>\u00a0SHANK3<\/em>\u00a0gene mutation identical to that in the mice.<\/p>\n<p>From these stem cells, they derived human oligodendrocytes with the same genetic profile. These oligodendrocytes displayed impairments similar to those observed in their mouse counterparts.<\/p>\n<p>Prof. Barak concludes: \u201cIn our study, we discovered two new brain mechanisms involved in genetically induced autism: damage to oligodendrocytes and, consequently, damage to the myelin they produce.<\/p>\n<p>\u201cThese findings have important implications \u2013 both clinical and scientific.\u00a0 Scientifically, we learned that defective myelin plays a significant role in autism and identified the mechanism causing the damage to myelin.<\/p>\n<p>\u201cAdditionally, we revealed a new role for the SHANK3 protein: building and maintaining a functional binding substrate for receptors critical for message reception in oligodendrocytes (not just in neurons). In fact, we discovered that contrary to the prevailing view, these cells play essential roles in their own right, far beyond the support they provide for neurons \u2014 often seen as the main players in the brain.<\/p>\n<p>\u201cIn the clinical sphere we validated a gene therapy approach that led to significantly improved development and function of oligodendrocytes derived from the brains of mice modeling autism.<\/p>\n<p>\u201cThis finding offers hope for developing genetic treatment for humans, which could improve the myelin production process in the brain.<\/p>\n<p>Furthermore, recognizing the significance of myelin impairment in autism\u2014whether linked to the\u00a0<em>SHANK3<\/em>\u00a0gene or not\u2014opens new pathways for understanding the brain mechanisms underlying autism and paves the way for future treatment development.\u201d<\/p>\n<h2 class=\"wp-block-heading\">About this genetics and autism research news<\/h2>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author: <\/strong><a href=\"http:\/\/neurosciencenews.com\/cdn-cgi\/l\/email-protection#f5a194808587b5819480908ddb819480db9496db9c99\" target=\"_blank\" rel=\"noreferrer noopener\">Noga Shahar<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/tau.ac.il\" target=\"_blank\" rel=\"noreferrer noopener\">Tel Aviv University<\/a><br \/><strong>Contact: <\/strong>Noga Shahar \u2013 Tel Aviv University<br \/><strong>Image: <\/strong>The image is credited to Neuroscience News<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Original Research:<\/strong> Open access.<br \/>\u201c<a href=\"https:\/\/doi.org\/10.1126\/sciadv.adl4573\" target=\"_blank\" rel=\"noreferrer noopener\">Shank3 mutation impairs glutamate signaling and myelination in ASD mouse model and human iPSC-derived OPCs<\/a>\u201d by Boaz Barak et al. <em>Science Advances<\/em><\/p>\n<hr class=\"wp-block-separator has-text-color has-pale-cyan-blue-color has-alpha-channel-opacity has-pale-cyan-blue-background-color has-background\"\/>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>Shank3 mutation impairs glutamate signaling and myelination in ASD mouse model and human iPSC-derived OPCs<\/strong><\/p>\n<p>Autism spectrum disorder (ASD) is characterized by social and neurocognitive impairments, with mutations of the\u00a0<em>SHANK3<\/em>\u00a0gene being prominent in patients with monogenic ASD.<\/p>\n<p>Using the InsG3680 mouse model with a\u00a0<em>Shank3<\/em>\u00a0mutation seen in humans, we revealed an unknown role for Shank3 in postsynaptic oligodendrocyte (OL) features, similar to its role in neurons. This was shown by impaired molecular and physiological glutamatergic traits of InsG3680-derived primary OL cultures.<\/p>\n<p> In vivo, InsG3680 mice exhibit significant reductions in the expression of key myelination\u2013related transcripts and proteins, along with deficits in myelin ultrastructure, white matter, axonal conductivity, and motor skills. Last, we observed significant impairments, with clinical relevance, in induced pluripotent stem cell\u2013derived OLs from a patient with the InsG3680 mutation.<\/p>\n<p>Together, our study provides insight into Shank3\u2019s role in OLs and reveals a mechanism of the crucial connection of myelination to ASD pathology.<\/p>\n<p> <!-- Form created by Optin Forms plugin by WPKube: create beautiful optin forms with ease! --> <!-- https:\/\/wpkube.com\/ --><!--optinforms-form5-container--> <!-- \/ Optin Forms --> <\/div>\n<p><script async src=\"https:\/\/pagead2.googlesyndication.com\/pagead\/js\/adsbygoogle.js?client=ca-pub-3711241968723425\"\r\n     crossorigin=\"anonymous\"><\/script>\r\n<ins class=\"adsbygoogle\"\r\n     style=\"display:block\"\r\n     data-ad-format=\"fluid\"\r\n     data-ad-layout-key=\"-fb+5w+4e-db+86\"\r\n     data-ad-client=\"ca-pub-3711241968723425\"\r\n     data-ad-slot=\"7910942971\"><\/ins>\r\n<script>\r\n     (adsbygoogle = window.adsbygoogle || []).push({});\r\n<\/script><br \/>\n<br \/><div data-type=\"_mgwidget\" data-widget-id=\"1660802\">\r\n<\/div>\r\n<script>(function(w,q){w[q]=w[q]||[];w[q].push([\"_mgc.load\"])})(window,\"_mgq\");\r\n<\/script>\r\n<br \/>\n<br \/><a href=\"https:\/\/neurosciencenews.com\/ahshank3-myelin-asd-therapy-28092\/\">Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Summary: Autism-linked SHANK3 gene mutations disrupt not only neurons but also oligodendrocytes, essential for producing myelin, which insulates nerve fibers. This damage reduces brain signal efficiency and impairs behavior. 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