Research News

Abstract: Kawasaki disease is an acute, self-limiting, systemic vasculitis of small and medium-sized arteries. It predominantly occurs in children under 4 years of age, though rarely older children can also be affected. This disease is the leading cause of acquired heart disease in children, with coronary aneurysms being a hallmark finding. The risk of coronary complications necessitates regular monitoring and possible preventative treatment with thromboprophylaxis. Here we discuss a rare case of a 10-year-old boy who exhibited typical symptoms of Kawasaki disease and was found to have multiple coronary artery aneurysms through diagnostic imaging.

Wagle G, Khatiwada A, Bastakoti S, K C S. Late onset Kawasaki disease with multiple coronary arterial aneurysms: A case report. Radiol Case Rep. 2024 Aug 10;19(11):4762-4765. doi: 10.1016/j.radcr.2024.07.066. PMID: 39228940; PMCID: PMC11366877.

https://pubmed.ncbi.nlm.nih.gov/39228940/

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1469614/pdf

Abstract:  “With new data about different aspects of schizophrenia being continually generated, it becomes necessary to periodically revisit exactly what we know. Along with a need to review what we currently know about schizophrenia, there is an equal imperative to evaluate the construct itself. With these objectives, we undertook an iterative, multi-phase process involving fifty international experts in the field, with each step building on learnings from the prior one. This review assembles currently established findings about schizophrenia (construct, etiology, pathophysiology, clinical expression, treatment) and posits what they reveal about its nature. Schizophrenia is a heritable, complex, multi-dimensional syndrome with varying degrees of psychotic, negative, cognitive, mood, and motor manifestations. The illness exhibits a remitting and relapsing course, with varying degrees of recovery among affected individuals with most experiencing significant social and functional impairment. Genetic risk factors likely include thousands of common genetic variants that each have a small impact on an individual’s risk and a plethora of rare gene variants that have a larger individual impact on risk. Their biological effects are concentrated in the brain and many of the same variants also increase the risk of other psychiatric disorders such as bipolar disorder, autism, and other neurodevelopmental conditions. Environmental risk factors include but are not limited to urban residence in childhood, migration, older paternal age at birth, cannabis use, childhood trauma, antenatal maternal infection, and perinatal hypoxia. Structural, functional, and neurochemical brain alterations implicate multiple regions and functional circuits. Dopamine D-2 receptor antagonists and partial agonists improve psychotic symptoms and reduce risk of relapse. Certain psychological and psychosocial interventions are beneficial. Early intervention can reduce treatment delay and improve outcomes. Schizophrenia is increasingly considered to be a heterogeneous syndrome and not a singular disease entity. There is no necessary or sufficient etiology, pathology, set of clinical features, or treatment that fully circumscribes this syndrome. A single, common pathophysiological pathway appears unlikely. The boundaries of schizophrenia remain fuzzy, suggesting the absence of a categorical fit and need to reconceptualize it as a broader, multi-dimensional and/or spectrum construct.“

Tandon R, Nasrallah H, Akbarian S, Carpenter WT Jr, DeLisi LE, Gaebel W, Green MF, Gur RE, Heckers S, Kane JM, Malaspina D, Meyer-Lindenberg A, Murray R, Owen M, Smoller JW, Yassin W, Keshavan M. The schizophrenia syndrome, circa 2024: What we know and how that informs its nature. Schizophr Res. 2024 Feb;264:1-28. doi: 10.1016/j.schres.2023.11.015. Epub 2023 Dec 12. PMID: 38086109.

https://pubmed.ncbi.nlm.nih.gov/38086109/

HYPOTHESIS AND THEORY article

Abstract:   “Animal personality, consistent individual differences in behaviour, is an important concept for understanding how individuals vary in how they cope with environmental challenges. In order to understand the evolutionary significance of animal personality, it is crucial to understand the underlying regulatory mechanisms. Epigenetic marks such as DNA methylation are hypothesised to play a major role in explaining variation in phenotypic changes in response to environmental alterations. Several characteristics of DNA methylation also align well with the concept of animal personality. In this review paper, we summarise the current literature on the role that molecular epigenetic mechanisms may have in explaining personality variation. We elaborate on the potential for epigenetic mechanisms to explain behavioural variation, behavioural development and temporal consistency in behaviour. We then suggest future routes for this emerging field and point to potential pitfalls that may be encountered. We conclude that a more inclusive approach is needed for studying the epigenetics of animal personality and that epigenetic mechanisms cannot be studied without considering the genetic background.”

van Oers K, van den Heuvel K, Sepers B. The epigenetics of animal personality. Neurosci Biobehav Rev. 2023 Jul;150:105194. doi: 10.1016/j.neubiorev.2023.105194. Epub 2023 Apr 23. PMID: 37094740.

https://www.sciencedirect.com/science/article/pii/S014976342300163X

Abstract: “Lactate is a critical metabolite during the body’s adaption to exercise training, which effectively relieves anxiety-like disorders. The biological mechanism of lactate in the exercise-mediated anxiolytic effect has, however, not been comprehensively investigated. Here, we report that exercise-induced lactate markedly potentiates the lactylation of multiple synaptic proteins, among which synaptosome-associated protein 91 (SNAP91) is the critical molecule for synaptic functions. Both anatomical evidence and in vivo recording data showed that the lactylation of SNAP91 confers resilience against chronic restraint stress (CRS) via potentiating synaptic structural formation and neuronal activity in the medial prefrontal cortex (mPFC). More interestingly, exercise-potentiated lactylation of SNAP91 is necessary for the prevention of anxiety-like behaviors in CRS mice. These results collectively suggest a previously unrecognized non-histone lactylation in the brain for modulating mental functions and provide evidence for the brain’s metabolic adaption during exercise paradigms.“

Yan L, Wang Y, Hu H, Yang D, Wang W, Luo Z, Wang Y, Yang F, So KF, Zhang L. Physical exercise mediates cortical synaptic protein lactylation to improve stress resilience. Cell Metab. 2024 Aug 9:S1550-4131(24)00289-4. doi: 10.1016/j.cmet.2024.07.018. Epub ahead of print. PMID: 39163863.

https://pubmed.ncbi.nlm.nih.gov/39163863/

https://www.cell.com/cell/fulltext/S0092-8674(24)00702-5

McCutcheon SR, Rohm D, Iglesias N, Gersbach CA. Epigenome editing technologies for discovery and medicine. Nat Biotechnol. 2024 Aug;42(8):1199-1217. doi: 10.1038/s41587-024-02320-1. Epub 2024 Jul 29. PMID: 39075148.

https://pubmed.ncbi.nlm.nih.gov/39075148/

“Reactive microglia contribute to Parkinson’s disease (PD) pathogenesis. Certain cytokines such as interleukin-10 (IL-10) can restore microglia homeostasis, but targeting maladaptive immune responses without inducing systemic side effects remains a challenge. Bido et al. adopted a microRNA-detargeting system that inhibits the expression of a transgene in all but the cell type of choice. Using this system for lentiviral-mediated, local, and microglia-specific expression of IL-10 in PD mice led to reduced neuropathology and the emergence of microglial subtypes with enhanced clearance signatures. These results suggest the therapeutic potential of cell type–specific gene delivery for PD. ”

Bido S et al.: Microglia-specific IL-10 gene delivery inhibits neuroinflammation and neurodegeneration in a mouse model of Parkinson’s disease. Science Translational Medicine 16 (761), (21 Aug 2024).

https://www.science.org/doi/10.1126/scitranslmed.adm8563