A lack of association between hyperserotonemia and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children |
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Authors: | Gehan Ahmed Mostafa Laila Yousef AL-Ayadhi |
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Institution: | 1. Department of Children’s Dentistry, Stony Brook University Health Science Center, Stony Brook, NY, 11794, USA 4. Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, 14620, USA 5. Neurobiology & Anatomy, School of Medicine & Dentistry, University of Rochester, Rochester, NY, 14642, USA 2. Department of Emergency Medicine, Stony Brook University Health Science Center, Stony Brook, NY, 11794, USA 3. Department of Oral Biology & Pathology, Stony Brook University Health Science Center, Stony Brook, NY, 11794, USA
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Abstract: | Background The purpose of this study was to investigate whether localized peripheral inflammation, such as osteoarthritis, contributes to neuroinflammation and neurodegenerative disease in vivo. Methods We employed the inducible Col1-IL1βXAT mouse model of osteoarthritis, in which induction of osteoarthritis in the knees and temporomandibular joints resulted in astrocyte and microglial activation in the brain, accompanied by upregulation of inflammation-related gene expression. The biological significance of the link between peripheral and brain inflammation was explored in the APP/PS1 mouse model of Alzheimer's disease (AD) whereby osteoarthritis resulted in neuroinflammation as well as exacerbation and acceleration of AD pathology. Results Induction of osteoarthritis exacerbated and accelerated the development of neuroinflammation, as assessed by glial cell activation and quantification of inflammation-related mRNAs, as well as Aβ pathology, assessed by the number and size of amyloid plaques, in the APP/PS1; Col1-IL1βXAT compound transgenic mouse. Conclusion This work supports a model by which peripheral inflammation triggers the development of neuroinflammation and subsequently the induction of AD pathology. Better understanding of the link between peripheral localized inflammation, whether in the form of osteoarthritis, atherosclerosis or other conditions, and brain inflammation, may prove critical to our understanding of the pathophysiology of disorders such as Alzheimer's, Parkinson's and other neurodegenerative diseases. |
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