Genomic deletion of TLR2 induces aggravated white matter damage and deteriorated neurobehavioral functions in mouse models of Alzheimer's disease.

Genomic deletion of TLR2 induces aggravated white matter damage and deteriorated neurobehavioral functions in mouse models of Alzheimer's disease. Aging (Albany NY). 2019 Sep 11;11: Authors: Zhou C, Sun X, Hu Y, Song J, Dong S, Kong D, Wang Y, Hua X, Han J, Zhou Y, Jin G, Yang X, Shi H, Zhang Z, Hua F Abstract Toll-like receptor-2 (TLR2), a member of the TLR family, plays an important role in the initiation and regulation of immune/inflammation response, which is a critical mechanism underlying Alzheimer's disease (AD). To clarify the role of TLR2 in the pathological process of AD, in the present study, TLR2 knockout plus APPswe/PSEN1dE9 transgenic mice (AD-TLR2KO) were generated. Neurobehavioral tests and brain MRI scan were conducted on mice at the age of 12 months. Additionally, neuron loss was evaluated using NeuN staining. Amyloid β protein (Aβ), glial fibrillary acidic protein (GFAP), endogenous ligands for TLR2, and the activation of downstream signaling of TLR2 in mouse brains were detected by immunohistochemistry and Western blots. The results demonstrated that TLR2 deficit induced learning disabilities, decreased spontaneous activity, increased anxiety and depression, and led to white matter damage (WMD), brain atrophy, loss of neurons, and glial activation. Moreover, TLR2 deficit aggravated impaired neurobehavioral functions and WMD in AD mice, but did not affect the Aβ deposition in mouse brains. Our data indicate that the geno...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research

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We reported DEGs with a nominal p-value of 0.8. The network construction was created using blockwiseModules function for consideration of computer efficiency. The module detection criteria were as follows: minimum module size of 50, deepsplit of 4, and merge threshold of 0.25. The merged modules were then summarized with module eigengene (ME) correlations>0.75. MEs were defined by their first principal component and were labeled with different colors as module names in the Results section. After the modules were generated, we conducted different enrichment analysis to explore the functional interpretation of genes withi...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Albert Sanfeliu1, Karsten Hokamp2, Michael Gill1 and Daniela Tropea1,3*1Neuropsychiatric Genetics, Department of Psychiatry, School of Medicine, Trinity Translational Medicine Institute, St James Hospital, Dublin, Ireland2Department of Genetics, School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland3Department of Psychiatry, School of Medicine, Trinity College Institute for Neuroscience, Trinity College Dublin, Dublin, IrelandRett syndrome is a rare neuropsychiatric disorder with a wide symptomatology including impaired communication and movement, cardio-respiratory abno...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Conclusion: Genetic associations of diseases considerably vary across populations which necessitates health-related genotyping efforts especially for so far understudied populations. SOM portrayal represents novel promising methods in population genetic research with special strength in visualization-based comparison of SNP data. Introduction Non-communicable polygenic diseases such as cancers, neurodegeneration, cardiovascular, and metabolic disorders have become the most prevalent type worldwide and account for the majority of death events in developed and transition economy countries (Habib and Saha, 2010; Benzi...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Wei Li1†, Wei-Min Xiao1†, Yang-Kun Chen1*, Jian-Feng Qu1, Yong-Lin Liu1, Xue-Wen Fang2, Han-Yu Weng1 and Gen-Pei Luo11Department of Neurology, Dongguan People’s Hospital, Dongguan, China2Department of Radiology, Dongguan People’s Hospital, Dongguan, ChinaBackground: Anxiety is prevalent after a stroke. The pathophysiological mechanisms underlying the development of poststroke anxiety (PSA) remain unclear. The aim of this study was to investigate the clinical and neuroimaging risk factors for development of PSA and examine the effects of PSA on activities of daily living (ADL) and quality of life (...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
ConclusionsDifferent patterns of sleep disturbances are observed in HD patients: insomnia, difficulties in falling asleep, frequent nocturnal awakenings, and excessive daytime sleepiness are the most common sleep problems reported by patients with HD. In several HD studies, specific changes in sleep architecture and in circadian melatonin secretion were identified in laboratory testing.Sleep disorders in HD have diverse and complex determinants, the most significant of which includes damage to brain areas that are responsible for the proper sleep pattern and circadian rhythm regulation. Sleep and circadian rhythm disorders...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
This article, unfortunately paywalled, is interesting to note as a mark of the now increasingly energetic expansion of commercial efforts in longevity science. David Sinclair has been building a private equity company to work in many areas relevant to this present generation of commercial longevity science; while I'm not sold on his primary research interests as the basis for meaningful treatments for aging, he is diversifying considerably here, including into senolytics, the clearance of senescent cells demonstrated to produce rejuvenation in animal studies. This sort of approach to business mixes aspects of investing and...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The Middle East and North Africa (MENA) face daunting challenges in managing a growing burden of mental illness, often in adverse conditions that can leave their imprint on generations to come.While the burden of mental-health conditions is above the global average in most MENA countries, the human resources, policies, funding and infrastructure to deal with these problems are sorely lacking.According to a recent study led by the Institute for Health Metrics and Evaluation (IHME), mental disorders excluding substance abuse accounted for 4.7% of all disability-adjusted life years (DALYs) in the World Health Organization &rs...
Source: EyeForPharma - Category: Pharmaceuticals Authors: Source Type: news
Imagine a world in which caring for the deeply forgetful is deemed a privilege and a trust.By Stephen PostAlzheimer's Reading RoomI do believe that we will see a spiritual-cultural shift away from the ideology of “hyper-cognitive values” that has regrettably blinded us to the enduring selves underlying the deeply forgetful.How can we encounter the deeply forgetful outside of hyper-cognitive ideologies?Dementia Patients are People TooHow can we bear witness to the reality that persons with this cognitive disability possess inherent qualities, and create a culture where all are welcomed and celebrated regardless ...
Source: Alzheimer's Reading Room, The - Category: Neurology Tags: alz alzheimers bond cruelty deeply forgetful dehumanizing others demenitia glass half full love privilege self identity Spiritual Cultural Evolution Stephen Post trust Source Type: blogs
Conclusion: This novel technology discriminates and quantifies subtle differences in behavior and neurological impairments in subjects afflicted with neurological injury/disease. KINARM assessments can be incorporated into multi-center trials (e.g., monitoring stroke motor recovery: NCT02928393). Further studies will determine if KINARM Labs can demonstrate a clinical effect with fewer subjects over a shorter trial period. Disclosures/funding: Dr. Stephen Scott is the inventor of KINARM and CSO of BKIN Technologies.   Multiplexed mass spectrometry assay identifies neurodegeneration biomarkers in CSF Presenter: Chelsky...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Assessment Tools biomarkers Cognition Current Issue Drug Development General Genetics Medical Issues Neurology Patient Assessment Psychopharmacology Scales Special Issues Supplements Trial Methodology clinical trials CNS Su Source Type: research
Publication date: 16–22 September 2017 Source:The Lancet, Volume 390, Issue 10100 Author(s): GBD 2016 Disease and Injury Incidence and Prevalence CollaboratorsAmanuel AlemuAbajobirKalkidan HassenAbateCristianaAbbafatiKaja MAbbasFoadAbd-AllahRizwan SuliankatchiAbdulkaderAbdishakur MAbdulleTeshome AbukaAbeboSemaw FeredeAberaVictorAboyansLaith JAbu-RaddadIlana NAckermanAbdu AbdullahiAdamuOlatunjiAdetokunbohMohsenAfaridehAshkanAfshinSanjay KumarAgarwalRakeshAggarwalAnuragAgrawalSutapaAgrawalHamidAhmadiehMuktar BeshirAhmedMiloud Taki EddineAichourAmani NidhalAichourIbtihelAichourSnehaAiyarRufus OlusolaAkinyemiNadiaAkseer...
Source: The Lancet - Category: General Medicine Source Type: research
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