Summary: University of Texas researchers report neurons in the mouse brain tend to surge at the equivalent of human age 40. During this period, interleukin33 also surges in healthy mice. In those lacking the gene, neurodegeneration occurred, eventually resulting in dementia.
Source: UT Health Science Center Houston.
Researchers at The University of Texas Health Science Center at Houston (UTHealth) School of Dentistry and McGovern Medical School have discovered a previously unknown characteristic of brain-cell aging that could help detect late-onset Alzheimer’s disease decades before symptoms begin.
The study, “Interleukin33 deficiency causes tau abnormality and neurodegeneration with Alzheimer-like symptoms in aged mice,” appeared online in the journal Translational Psychiatry earlier this year.
Working with mice, the UTHealth team found that neurons in the brain experienced a sudden increase in aging around the mouse equivalent of age 40 in humans. Normal mice responded with a surge of interleukin33, a protein that activates the body’s repair mechanisms to make the neurons healthy again. Mice lacking the IL33 gene didn’t experience the surge and continued to decline, eventually developing dementia at an age roughly equivalent to 68 in humans.
“We think we’re getting old gradually, but when we’re talking about these cells, we’ve discovered that it’s not that way,” said Yahuan Lou, Ph.D., a professor in the Department of Diagnostic and Biomedical Sciences at the School of Dentistry.
Late-onset sporadic Alzheimer’s disease occurs after age 65 and represents approximately 95 percent of all cases, with the other 5 percent believed to be genetic. By the time symptoms appear, the brain has already lost massive numbers of neurons. The UTHealth researchers believe the surge at age 40 may be an ideal time to look for biomarkers that predict Alzheimer’s long before the damage begins.
Lou first detected the power of IL33 while studying premature ovarian failure in mice. “We observed that when we removed IL33, the ovary shrank much faster than normal. So we wondered: If IL33 does this in the ovary, what does it do in the brain? The brain has an abundance of IL33.”
Looking for collaborators who could test that question, Lou was surprised to learn that researchers from McGovern Medical School’s Department of Psychiatry and Behavioral Sciences had recently moved into the new UT Behavioral and Biomedical Sciences Building that he and other dental school researchers had also newly occupied. Among his new neighbors were Department of Psychiatry Professor Joao De Quevedo, M.D., Ph.D., and Assistant Professor Ines Moreno-Gonzalez, Ph.D., of the Mitchell Center for Alzheimer’s Disease, who had the expertise and resources for analyzing rodent behavior and correlating it to humans. A collaborative team soon formed, and their mouse study led to the paper in Translational Psychiatry with plans for follow-up studies to explore the tantalizing results.
Lou said a group of researchers in Singapore recently conducted an experiment using mice that model familial early-onset Alzheimer’s disease. “When they injected IL33 into the [Alzheimer’s] mice, they saw that the plaque load was reduced, but they didn’t know why,” he said. “We’ve figured out why.”
The IL33 injections seemed to relieve symptoms temporarily, he added, but did not cure the disease. The effects lasted about two weeks in mice — equal to several months in humans. Lou believes finding a way to enhance the brain’s own supply of IL33 may lead to potential treatments for the disease.
The cause of late-onset Alzheimer’s is a medical mystery with many potential causes under investigation, including neuro-inflammation, abnormal aging, smoking, and infections. IL33 deficiency is another promising lead, with additional studies planned as funding is secured.
Source: Rob Cahill – UT Health Science Center Houston Publisher: Organized by NeuroscienceNews.com. Image Source: NeuroscienceNews.com image is in the public domain. Original Research: Full open access research for “Interleukin33 deficiency causes tau abnormality and neurodegeneration with Alzheimer-like symptoms in aged mice” by C Carlock, J Wu, J Shim, I Moreno-Gonzalez, M R Pitcher, J Hicks, A Suzuki, J Iwata, J Quevado & Y Lou in Translational Psychiatry. Published online July 4 2017 doi:10.1038/tp.2017.142
Cite This NeuroscienceNews.com Article
[cbtabs][cbtab title=”MLA”]UT Health Science Center Houston “Brain’s Response to Mid-Life Surge in Cell Aging Starts or Ends Path to Dementia.” NeuroscienceNews. NeuroscienceNews, 30 October 2017. <https://neurosciencenews.com/cell-aging-mid-life-dementia-7836/>.[/cbtab][cbtab title=”APA”]UT Health Science Center Houston (2017, October 30). Brain’s Response to Mid-Life Surge in Cell Aging Starts or Ends Path to Dementia. NeuroscienceNews. Retrieved October 30, 2017 from https://neurosciencenews.com/cell-aging-mid-life-dementia-7836/[/cbtab][cbtab title=”Chicago”]UT Health Science Center Houston “Brain’s Response to Mid-Life Surge in Cell Aging Starts or Ends Path to Dementia.” https://neurosciencenews.com/cell-aging-mid-life-dementia-7836/ (accessed October 30, 2017).[/cbtab][/cbtabs]
Interleukin33 deficiency causes tau abnormality and neurodegeneration with Alzheimer-like symptoms in aged mice
Late-onset Alzheimer’s disease (AD) remains a medical mystery. Recent studies have linked it to impaired repair of aged neurons. Potential involvement of interleukin33 (IL33) in AD has been reported. Here we show that IL33, which was expressed by up to 75% astrocytes in the aged brains, was critical for repair of aged neurons. Mice lacking Il33 gene (Il33−/−) developed AD-like disease after 60–80 weeks, which was characterized by tau abnormality and a heavy loss of neurons/neurites in the cerebral cortex and hippocampus accompanied with cognition/memory impairment. We detected an abrupt aging surge in the cortical and hippocampal neurons at middle age (40 weeks). To counter the aging surge, wild-type mice rapidly upregulated repair of DNA double-strand breaks (DSBs) and autophagic clearance of cellular wastes in these neurons. Il33−/− mice failed to do so, but instead went on to develop rapid accumulation of abnormal tau, massive DSBs and abnormal autophagic vacuoles in these neurons. Thus, uncontrolled neuronal aging surge at middle age due to lack of IL33 resulted in neurodegeneration and late-onset AD-like symptome in Il33−/− mice. Our study also suggests that the aging surge is a time to search for biomarkers for early diagnosis of AD before massive neuron loss.
“Interleukin33 deficiency causes tau abnormality and neurodegeneration with Alzheimer-like symptoms in aged mice” by C Carlock, J Wu, J Shim, I Moreno-Gonzalez, M R Pitcher, J Hicks, A Suzuki, J Iwata, J Quevado & Y Lou in Translational Psychiatry. Published online July 4 2017 doi:10.1038/tp.2017.142