Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour
Anthony J. Filiano,Yang Xu,Nicholas J. Tustison,Rachel Marsh,Wendy Baker,Igor Smirnov,Christopher C. Overall,Sachin P. Gadani,Stephen D. Turner,Zhiping Weng,Sayeda Najamussahar Peerzade,Hao Chen,Kevin S. Lee,Michael Scott,Mark P. Beenhakker,Vladimir Litvak,Jonathan Kipnis +16 more
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TLDR
It is shown that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions, and suggests a co-evolutionary link between social behaviour and an anti-pathogen immune response driven by IFN-γ signalling.Abstract:
Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory. Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions. Associations between rodent transcriptomes from brain and cellular transcriptomes in response to T-cell-derived cytokines suggest a strong interaction between social behaviour and interferon-γ (IFN-γ)-driven responses. Concordantly, we demonstrate that inhibitory neurons respond to IFN-γ and increase GABAergic (γ-aminobutyric-acid) currents in projection neurons, suggesting that IFN-γ is a molecular link between meningeal immunity and neural circuits recruited for social behaviour. Meta-analysis of the transcriptomes of a range of organisms reveals that rodents, fish, and flies elevate IFN-γ/JAK-STAT-dependent gene signatures in a social context, suggesting that the IFN-γ signalling pathway could mediate a co-evolutionary link between social/aggregation behaviour and an efficient anti-pathogen response. This study implicates adaptive immune dysfunction, in particular IFN-γ, in disorders characterized by social dysfunction and suggests a co-evolutionary link between social behaviour and an anti-pathogen immune response driven by IFN-γ signalling.read more
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The Microbiota-Gut-Brain Axis
John F. Cryan,Kenneth J. O’Riordan,Caitlin S. M. Cowan,Kiran V. Sandhu,Thomaz F.S. Bastiaanssen,Marcus Boehme,Martín Gabriel Codagnone,Sofia Cussotto,Christine Fülling,Anna V. Golubeva,Katherine E. Guzzetta,Minal Jaggar,Caitriona M. Long-Smith,Joshua M. Lyte,Jason A. Martin,Alicia Molinero-Perez,Gerard M. Moloney,Emanuela Morelli,Enrique Morillas,Rory C. O'Connor,Joana S Cruz-Pereira,Veronica L. Peterson,Kieran Rea,Nathaniel L. Ritz,Eoin Sherwin,Simon Spichak,Emily M. Teichman,Marcel van de Wouw,Ana Paula Ventura-Silva,Shauna E. Wallace-Fitzsimons,Niall P. Hyland,Gerard Clarke,Timothy G. Dinan +32 more
TL;DR: Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
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IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy.
TL;DR: This Review focuses on recent advances in the understanding of the transcriptional, chromatin-based and metabolic mechanisms that underlie IFNγ-mediated polarization of macrophages to an ‘M1-like’ state, which is characterized by increased pro-inflammatory activity and macrophage resistance to tolerogenic and anti-inflammatory factors.
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Understanding the functions and relationships of the glymphatic system and meningeal lymphatics
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A Breakdown in Metabolic Reprogramming Causes Microglia Dysfunction in Alzheimer's Disease.
Sung Hoon Baik,Seokjo Kang,Woochan Lee,Hayoung Choi,Sunwoo Chung,Jong Il Kim,Inhee Mook-Jung +6 more
TL;DR: It was found that exposure to amyloid-β triggers acute microglial inflammation accompanied by metabolic reprogramming from oxidative phosphorylation to glycolysis, and it was shown that metabolic boosting with recombinant interferon-γ treatment reversed the defective Glycolytic metabolism and inflammatory functions of microglia, thereby mitigating the AD pathology of 5XFAD mice.
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