{"id":823,"date":"2020-09-22T16:06:09","date_gmt":"2020-09-22T20:06:09","guid":{"rendered":"https:\/\/med.virginia.edu\/big\/?p=823"},"modified":"2020-09-23T21:14:33","modified_gmt":"2020-09-24T01:14:33","slug":"brain-discovery-could-have-important-implications-for-neurodegenerative-diseases","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/big\/2020\/09\/22\/brain-discovery-could-have-important-implications-for-neurodegenerative-diseases\/","title":{"rendered":"Brain Discovery Could Have Important Implications for Neurodegenerative Diseases"},"content":{"rendered":"

\"Lukens<\/p>\n

April 2020 – I<\/span>mproper removal of faulty brain cells during neurodevelopment may cause lifelong behavioral issues, new research from the University of Virginia School of Medicine suggests. The finding also could have important implications for a wide range of neurodegenerative diseases, such as Alzheimer\u2019s and Parkinson\u2019s diseases.<\/p>\n

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UVA neuroscientists have discovered that an unexpected form of cellular cleanup takes place in developing brains. If this process goes wrong \u2013 happening too little or too much \u2013 it can cause permanent changes in the brain\u2019s wiring. In lab mice, this results in anxiety-like behavior, and it may play a role in neurological conditions such as autism in humans.<\/p>\n

\u201cYou don\u2019t want [brain] cells to have genomic compromises. You don\u2019t want damaged DNA. So, this would be a normal mechanism to expel those cells from being incorporated into the central nervous system,\u201d researcher Catherine R. Lammert explained. \u201cWhen the damage isn\u2019t recognized, the cells that have DNA damage live on in the [central nervous system] and can be seen by accumulation of DNA damage in the brain.\u201d<\/p>\n

Understanding Brain Development<\/strong><\/h2>\n

The cellular cleaner the researchers spotted, the AIM2 inflammasome, has been associated primarily with the body\u2019s immune response to infections, but has not been extensively studied in the brain. But there it plays a critical role in ensuring the developing brain is assembled properly and functions correctly, Lammert discovered in collaboration with principal investigator John Lukens.<\/p>\n

\u201cNeurodevelopment is a very complicated process,\u201d said Lammert, a graduate student whose specialized skills were instrumental in the discovery. \u201cThis form of cell death actually plays a role in removing unwanted cells from the brain to establish a healthy [central nervous system] with the correct connections and the right number of cells.\u201d<\/p>\n

More than half the neurons created during brain development end up dying, so proper cleanup is essential, noted Lukens, of UVA\u2019s Department of Neuroscience. \u201cToo much or too little is thought to underlie everything from autism to intellectual disability \u2013\u00a0any type of neurodevelopmental disorder,\u201d he said.<\/p>\n

For example, ataxia is a condition that causes people to lose control of their movements. \u201cThere\u2019s a potential that this pathway could be contributing to the neuronal loss that is seen in ataxia,\u201d said Lukens, a researcher with UVA\u2019s Center for Brain Immunology and Glia, or BIG. \u201cOn the one hand, you need it [the cleanup], but if you have too much of it, it can have negative consequences, like, potentially, ataxia. A lot of the early-onset neurodegenerative diseases are associated with mutations in DNA damage repair proteins, and this pathway could also be involved.\u201d<\/p>\n

The discovery came about somewhat serendipitously, the result of an observation of the behavior of lab mice while the researchers were investigating traumatic brain injury. But following that unexpected lead has given scientists a better understanding of brain development, and that understanding may one day yield new treatments for neurological diseases.<\/p>\n

Lukens, a member of UVA\u2019s Carter Immunology Center, cautioned that such treatments are likely a long way off, but he said a therapy based on the discovery might have widespread applications.<\/p>\n

\u201cHitting this pathway in the mature brain would likely provide a treatment strategy for any neurodegenerative disease associated with DNA damage,\u201d he said. \u201cAnd that\u2019s all the major heavy hitters: Alzheimer\u2019s disease, Parkinson\u2019s, ALS.\u201d<\/p>\n

Findings Published<\/strong><\/h2>\n

The researchers have\u00a0published their findings in the prestigious journal Nature<\/strong><\/a>. The study\u2019s authors were Lammert, Elizabeth L. Frost, Calli E. Bellinger, Ashley C. Bolte, Celia A. McKee, Mariah E. Hurt, Matt J. Paysour, Hannah E. Ennerfelt and Lukens.<\/p>\n

The research was supported by the Hartwell Foundation; Rettsyndrome.org grant 22349; the Owens Family Foundation; and Brain & Behavior Research Foundation grant 27515. Lammert was supported by a predoctoral training grant from the National Institutes of Health\u2019s National Institute of General Medical Sciences and a Wagner Fellowship.<\/em><\/p>\n

To keep up with the latest medical research news from UVA, subscribe to the\u00a0<\/em>Making of Medicine<\/em><\/strong><\/a>\u00a0blog.<\/em><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

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By Josh Barney, jdb9a@virginia.edu,<\/a><\/span>\u00a0434-906-8864<\/span><\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

April 2020 – Improper removal of faulty brain cells during neurodevelopment may cause lifelong behavioral issues, new research from the University of Virginia School of Medicine suggests. The finding also could have important implications for a wide range of neurodegenerative diseases, such as Alzheimer\u2019s and Parkinson\u2019s diseases. 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