https://www.nature.com/articles/d41586-021-02039-y
Nature. 2021 Jul;595(7869):640-644.


doi: 10.1038/d41586-021-02039-y

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https://www.nature.com/articles/s41582-021-00531-7.pdf

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https://www.pnas.org/content/pnas/118/24/e2013155118.full.pdf

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190281/pdf/41467_2021_Article_23694.pdf

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Abstract: “While many diseases of aging have been linked to the immunological system, immune metrics capable of identifying the most at-risk individuals are lacking. From the blood immunome of 1,001 individuals aged 8–96 years, we developed a deep-learning method based on patterns of systemic age-related inflammation. The resulting inflammatory clock of aging (iAge) tracked with multimorbidity, immunosenescence, frailty and cardiovascular aging, and is also associated with exceptional longevity in centenarians. The strongest contributor to iAge was the chemokine CXCL9, which was involved in cardiac aging, adverse cardiac remodeling and poor vascular function. Furthermore, aging endothelial cells in human and mice show loss of function, cellular senescence and hallmark phenotypes of arterial stiffness, all of which are reversed by silencing CXCL9. In conclusion, we identify a key role of CXCL9 in age-related chronic inflammation and derive a metric for multimorbidity that can be utilized for the early detection of age-related clinical phenotypes.”

Sayed, N., Huang, Y., Nguyen, K. et al. An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nat Aging 1, 598–615 (2021). https://doi.org/10.1038/s43587-021-00082-y.

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COVID and the brain: researchers zero in on how damage occurs.

Nature News July 7, 2021.
“Growing evidence suggests that the coronavirus causes ‘brain fog’ and other neurological symptoms through multiple mechanisms….

How COVID-19 damages the brain is becoming clearer. New evidence suggests that the coronavirus’s assault on the brain could be multipronged: it might attack certain brain cells directly, reduce blood flow to brain tissue or trigger production of immune molecules that can harm brain cells.Infection with the coronavirus SARS-CoV-2 can cause memory loss, strokes and other effects on the brain. The question, says Serena Spudich, a neurologist at Yale University in New Haven, Connecticut, is: “Can we intervene early to address these abnormalities so that people don’t have long-term problems?” With so many people affected — neurological symptoms appeared in 80% of the people hospitalized with COVID-19 who were surveyed in one study1 — researchers hope that the growing evidence base will point the way to better treatments….”

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Makhani, N., Tremlett, H. The multiple sclerosis prodrome. Nat Rev Neurol (2021). https://doi.org/10.1038/s41582-021-00519-3

https://www.nature.com/articles/s41582-021-00519-3

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Summary:
“The molecular mechanisms accounting for the environmental risk factor stimulation of Alzheimer’s disease (AD) pathogenesis including traumatic brain injury, diabetes, and chronic cerebral hypoperfusion remain unclear. The BDNF/TrkB signaling pathway plays a critical role in neuronal synaptic plasticity and neuronal survival. Since the BDNF/TrkB pathway is reduced during aging and in AD human brains, we hypothesize that the crosstalk between these risk factors and BDNF/TrkB deficiency may mediate AD pathologies. Our previous studies establish that the C/EBPβ/δ-secretase pathway plays a pivotal role in triggering the major AD pathologies. Therefore, in the current report, we provide extensive evidence demonstrating that BDNF/TrkB reduction regulates this pathway activation under various risk factors, mediating Aβ and Tau pathology spreading in the brain.”

https://www.pnas.org/content/118/25/e2100986118

 

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Abstract:
“Though SARS-CoV-2 primarily targets the respiratory system, patients and survivors can suffer neurological symptomsYet, an unbiased understanding of the cellular and molecular processes affected in the brains of COVID-19 patients is still missing. Here, we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control (including 1 terminal influenza) and 8 COVID-19 patients. While a systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, we observe broad cellular perturbations which predict that choroid plexus barrier cells sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma. We discover COVID-19 disease-associated microglia and astrocyte subpopulations that share features with pathological cell states reported in human neurodegenerative diseaseSynaptic signaling of upper-layer excitatory neurons—evolutionarily expanded in humans and linked to cognitive function —are preferentially affected in COVID-19. Across cell types, COVID-19 perturbations overlap with those in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia, and depression. Our findings and public dataset provide a molecular framework to understand COVID-19 related neurological disease observed now and which may emerge later.”

Yang, A.C., Kern, F., Losada, P.M. et al. Dysregulation of brain and choroid plexus cell types in severe COVID-19. Nature (2021). https://doi.org/10.1038/s41586-021-03710-0

https://www.nature.com/articles/s41586-021-03710-0

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“Curiosity is what drives organisms to investigate each other and their environment. It is considered by many to be as intrinsic as hunger and thirst, but the neurobiological mechanisms behind curiosity have remained elusive. In mice, Ahmadlou et al. found that a specific population of genetically identified γ-aminobutyric acid (GABA)—ergic neurons in a brain region called the zona incerta receive excitatory input in the form of novelty and/or arousal information from the prelimbic cortex, and these neurons send inhibitory projections to the periaqueductal gray region. This circuitry is necessary for the exploration of new objects and conspecifics.”

Ahmadlou M, Houba JHW, van Vierbergen JFM, Giannouli M, Gimenez GA, van Weeghel C, Darbanfouladi M, Shirazi MY, Dziubek J, Kacem M, de Winter F, Heimel JA. A cell type-specific cortico-subcortical brain circuit for investigatory and novelty-seeking behavior. Science. 2021 May 14;372(6543):eabe9681.

https://pubmed.ncbi.nlm.nih.gov/33986154/

 

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