“When fruit flies endure sleeplessness, cells in their guts accumulate toxic molecules that break down their DNA. Similar toxins were spotted in sleep-deprived mice. And when the sleepless flies were given antioxidants that prevent such build-up, they reached a normal fly life span. “‘They’re alive!’ And not only were they alive, they looked good,” says developmental neuroscientist Dragana Rogulja. The results suggest that although most sleep studies focus on the brain, lack of sleep kills by damaging other organs.”
Sleep deprivation leads to ROS accumulation in the fly and mouse gut
Gut-accumulated ROS trigger oxidative stress in this organ
Preventing ROS accumulation in the gut allows survival without sleep in flies
”Hardening of the arteries (atherosclerosis) was linked to dementia long ago, but subsequently, Alzheimer’s plaques and tangles have received more attention. A new proteome-wide association study unveils molecular links between intracranial atherosclerosis and dementia, independent of other pathologies, providing new evidence for one of the oldest suspected causes of dementia.”
Iadecola C: Revisiting atherosclerosis and dementia. Nature Neuroscience 23: 691-692 (2020).
Modulation of the sigma-1 receptor-IRE1 Pathway Is Beneficial in Preclinical Models of Inflammation and Sepsis
APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline
Understanding Parkinson’s Disease: video
The neuroinvasive potential of SARS‐CoV2 may play a role in the respiratory failure of COVID‐19 patients
Nataf S: An alteration of the dopamine synthetic pathway is possibly involved in the pathophysiology of COVID-19. J Med Virol. [Epub ahead of print, Apr. 4, 2020; doi: 10.1002/jmv.25826].
Abstract: “Chronic low-grade inflammation has been observed in major depression and other major psychiatric disorders and has been implicated in metabolic changes that are commonly associated with these disorders. This raises the possibility that the effects of dysfunctional metabolism may facilitate changes in neuronal structure and function which contribute to neuroprogression. Such changes may have implications for the progress from major depression to dementia in the elderly patient. The purpose of this review is to examine the contribution of inflammation and hypercortisolaemia, which are frequently associated with major depression, to neurodegeneration and how they detrimentally impact on brain energy metabolism. A key factor in these adverse events is insulin insensitivity caused by pro-inflammatory cytokines in association with desensitised glucocorticoid receptors. Identifying the possible metabolic changes initiated by inflammation opens new targets to ameliorate the adverse metabolic changes. This has resulted in the identification of dietary and drug targets which are of interest in the development of a new generation of psychotropic drugs.”
Leonard BE and Wegener G: Inflammation, insulin resistance and neuroprogression in depression. Acta Neuropsychiatr.32(1): 1-9 (2020).
Abstract: “Psoriasis is a common non-communicable chronic immune-mediated skin disease, affecting approximately 125 million people in the world. Its pathogenesis results from a combination of genetic and environmental factors. The pathogenesis of psoriasis seems to be driven by the interaction between innate immune cells, adaptive immune cells and keratinocytes, in a process mediated by cytokines (including interleukins (IL)-6, IL-17 and IL-22, interferon and tumor necrosis factor) and other signaling molecules. This leads to an inflammatory process with increased proliferation of epidermal cells, neo-angiogenesis and infiltration of dendritic cells in the skin. Dysfunctional de novo glucocorticoid synthesis in psoriatic keratinocytes and the skin microbiome have also been suggested as mediators in the pathogenesis of this disease. To understand psoriasis, it is essential to comprehend the processes underlying the skin immunity and neuroendocrinology. This review paper focuses on the skin as a neuroendocrine organ and summarizes what is known about the skin immune system, the brain-skin connection and the role played by the serotonergic system in skin. Subsequently, the alterations of neuroimmune processes and of the serotonergic system in psoriatic skin are discussed, as well as, briefly, the genetic basis of psoriasis.”
Martins AM, Ascenso A, Ribeiro HM, Marto J: The Brain-Skin Connection and the Pathogenesis of Psoriasis: A Review with a Focus on the Serotonergic System. Cells 2020 Mar 26;9(4). pii: E796. doi: 10.3390/cells9040796.