Editorial: The role of inflammation in neurodegenerative and psychiatric disorders DOI Creative Commons
Dirk M. Hermann,

Mingyue Zhang,

Anfei Huang

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: March 11, 2025

Inflammation plays a pivotal role in the pathogenesis of neurodegenerative disorders, such as ischemic stroke and Alzheimer's disease, psychiatric namely anxiety depression. Neuroinflammatory responses contribute to neuronal loss diseases 1,2,3 . In stroke, fatigue, depression have been described part cognitive deficits sickness behavior, which unlike focal neurological are strongly dependent on cytokine levels 4 Subtle neuroinflammation associated with activation indoleamine-2,3 dioxygenase-1 pathway is central hallmark major depressive disorder 5 Brain inflammatory predispose oxidative stress, neurotransmitter dysbalance, growth outgrowth disturbances synaptic plasticity disorders 2,3 conditions Targeting neuroinflammatory thus may represent promising way for promoting outcomes both disease groups.Neurodegenerative impose significant health burden, especially older individuals. The association between that develop later life issues often arise during adolescence or middle age supported by epidemiological studies 6 Experimental pointed out associations brain immune surveillance encouraging clinical treatment trials 7,8 Given intricate biology underlying there still numerous critical questions demand attention. It vital elucidate mechanisms enable development new strategies. Therefore, objective this Research Topic was further delve into inflammation diseases, aiming uncover be therapeutically targeted enhancing outcomes. This published four original research papers, illustrate current activities neuroinflammation, neurodegeneration fields an exemplary way. Brain-invading polymorphonuclear neutrophils lymphocytes play key roles injury 1,9 neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR) lymphocyte-to-monocyte (LMR) peripheral blood previously shown outcome 10,11 , NLR has specifically delirium after 12 article Wang et al. 13 who evaluated 1436 patients without dementia Medical Information Mart Intensive Care (MIMIC)-IV database requiring intensive care unit (ICU) admission, 214 (14.9%) were found delirium. multivariate logistic regression analysis, highest quartile (odds [OR] 2.080, 95% confidence interval [CI], 1.282-3.375) LMR (OR 0.503, CI 0.317-0.798) second PLR 1.574, 1.019-2.431) significantly A restricted cubic spline function showed progressive increase risk higher lower LMR, while Mendelian randomization analysis only negatively data underline relevance leukocyte markers memory disturbances. Future will define molecular mechanisms.Oxidative stress contributor cell damage, via oxidation lipid membranes. Lipoxygenases (LOXs) family lipid-oxidizing enzymes, generate eicosanoids related compounds from arachidonic acid other polyunsaturated fatty acids 14 12/15-LOX special it can directly oxidize membranes containing acids, preceding action phospholipase, leading direct attack organelles 15 presumably underlies cytotoxic activity 12/15-LOX, upregulated neurons endothelial cells their article, Cakir-Aktas 16 exposed mice transient proximal cerebral artery occlusion (MCAo) effect inhibitor ML351 (50 mg/kg) damage. Infarct volume, deficits, peroxidation, pro-inflammatory (interleukin-1β, interleukin-6, tumor necrosis factorα) attenuated inhibition, NOD-like receptor protein (NLRP)-1 -3 signaling non-neuronal These results suggest inhibition suppresses ischemia-induced acute subacute phases suppressing inflammasome activation.Via tripartite synapses, astrocytes transmission 17 Astrocytes involved dysfunction (AD) 18 AD imbalanced cholesterol metabolism, demonstrated high side-chain oxidized known 27-hydroxycholesterol (27-OH), abolish connectivity maturation. Spanos 19 reported downregulation glutamate transporters together increased glial fibrillary acidic hippocampus CYP27Tg mice, mouse model oxysterol dysbalance. Glutamate transporter-1 (GLT-1) also observed when wildtype fed high-cholesterol diets. To study relationship neurons, 3D co-culture system used, reproduced effects 27-OH 2D vivo Moreover, authors novel degenerative did not appear cultures, GLT-1 glutamate-aspartate transporter (GLAST) proposed dysregulation leads hyperexcitability dysfunction. Taken together, these report mechanism linking imbalance through astrocyte function.GATA1 member GATA transcription factor hematopoietic 20 GATA1 dorsolateral prefrontal cortex suffering depression, where act transcriptional repressor synapse-related genes 21 Building upon earlier works, Choi 22 investigated how globally altered gene expression using multi-omics approaches. Through combined analyses ChIPseq, mRNAseq, small RNAseq, profiled potentially affected cultured cortical Gene Ontology revealed might immune-related functions Hypothesizing induces activation, detrimental including synapse depressive-like first performed microglial morphometric overexpressing brains. Fractal ramification process length microglia decreased brains exhibiting overexpression, suggesting increases flow cytometry immunohistochemical activated phenotypes characterized CD86 CD68 Finally, they overexpression behavior could blocked inhibiting show centrally GATA1's behavior.This provides take home messages: (1) Peripheral responses, neutrophil, lymphocyte platelet counts, valuable predictors allow identification developing (2) Lipoxygenases, post-ischemic damage NLRP-1 -3-dependent activation. (3) decreases GLT1 GLAST astrocytes, evokes neuronal-astrocyte co-cultures. (4) behavior. Together, papers emphasize interplay diverse types (neurons, microglia, leukocytes) degenerating brain, maintain injury, most notably membrane structures, disturb integrity function. With respect processes, share surprisingly large number mechanisms. if treatments suitable one area similar application another one. foster translation psychiatry fields.

Language: Английский

Editorial: The role of inflammation in neurodegenerative and psychiatric disorders DOI Creative Commons
Dirk M. Hermann,

Mingyue Zhang,

Anfei Huang

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: March 11, 2025

Inflammation plays a pivotal role in the pathogenesis of neurodegenerative disorders, such as ischemic stroke and Alzheimer's disease, psychiatric namely anxiety depression. Neuroinflammatory responses contribute to neuronal loss diseases 1,2,3 . In stroke, fatigue, depression have been described part cognitive deficits sickness behavior, which unlike focal neurological are strongly dependent on cytokine levels 4 Subtle neuroinflammation associated with activation indoleamine-2,3 dioxygenase-1 pathway is central hallmark major depressive disorder 5 Brain inflammatory predispose oxidative stress, neurotransmitter dysbalance, growth outgrowth disturbances synaptic plasticity disorders 2,3 conditions Targeting neuroinflammatory thus may represent promising way for promoting outcomes both disease groups.Neurodegenerative impose significant health burden, especially older individuals. The association between that develop later life issues often arise during adolescence or middle age supported by epidemiological studies 6 Experimental pointed out associations brain immune surveillance encouraging clinical treatment trials 7,8 Given intricate biology underlying there still numerous critical questions demand attention. It vital elucidate mechanisms enable development new strategies. Therefore, objective this Research Topic was further delve into inflammation diseases, aiming uncover be therapeutically targeted enhancing outcomes. This published four original research papers, illustrate current activities neuroinflammation, neurodegeneration fields an exemplary way. Brain-invading polymorphonuclear neutrophils lymphocytes play key roles injury 1,9 neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR) lymphocyte-to-monocyte (LMR) peripheral blood previously shown outcome 10,11 , NLR has specifically delirium after 12 article Wang et al. 13 who evaluated 1436 patients without dementia Medical Information Mart Intensive Care (MIMIC)-IV database requiring intensive care unit (ICU) admission, 214 (14.9%) were found delirium. multivariate logistic regression analysis, highest quartile (odds [OR] 2.080, 95% confidence interval [CI], 1.282-3.375) LMR (OR 0.503, CI 0.317-0.798) second PLR 1.574, 1.019-2.431) significantly A restricted cubic spline function showed progressive increase risk higher lower LMR, while Mendelian randomization analysis only negatively data underline relevance leukocyte markers memory disturbances. Future will define molecular mechanisms.Oxidative stress contributor cell damage, via oxidation lipid membranes. Lipoxygenases (LOXs) family lipid-oxidizing enzymes, generate eicosanoids related compounds from arachidonic acid other polyunsaturated fatty acids 14 12/15-LOX special it can directly oxidize membranes containing acids, preceding action phospholipase, leading direct attack organelles 15 presumably underlies cytotoxic activity 12/15-LOX, upregulated neurons endothelial cells their article, Cakir-Aktas 16 exposed mice transient proximal cerebral artery occlusion (MCAo) effect inhibitor ML351 (50 mg/kg) damage. Infarct volume, deficits, peroxidation, pro-inflammatory (interleukin-1β, interleukin-6, tumor necrosis factorα) attenuated inhibition, NOD-like receptor protein (NLRP)-1 -3 signaling non-neuronal These results suggest inhibition suppresses ischemia-induced acute subacute phases suppressing inflammasome activation.Via tripartite synapses, astrocytes transmission 17 Astrocytes involved dysfunction (AD) 18 AD imbalanced cholesterol metabolism, demonstrated high side-chain oxidized known 27-hydroxycholesterol (27-OH), abolish connectivity maturation. Spanos 19 reported downregulation glutamate transporters together increased glial fibrillary acidic hippocampus CYP27Tg mice, mouse model oxysterol dysbalance. Glutamate transporter-1 (GLT-1) also observed when wildtype fed high-cholesterol diets. To study relationship neurons, 3D co-culture system used, reproduced effects 27-OH 2D vivo Moreover, authors novel degenerative did not appear cultures, GLT-1 glutamate-aspartate transporter (GLAST) proposed dysregulation leads hyperexcitability dysfunction. Taken together, these report mechanism linking imbalance through astrocyte function.GATA1 member GATA transcription factor hematopoietic 20 GATA1 dorsolateral prefrontal cortex suffering depression, where act transcriptional repressor synapse-related genes 21 Building upon earlier works, Choi 22 investigated how globally altered gene expression using multi-omics approaches. Through combined analyses ChIPseq, mRNAseq, small RNAseq, profiled potentially affected cultured cortical Gene Ontology revealed might immune-related functions Hypothesizing induces activation, detrimental including synapse depressive-like first performed microglial morphometric overexpressing brains. Fractal ramification process length microglia decreased brains exhibiting overexpression, suggesting increases flow cytometry immunohistochemical activated phenotypes characterized CD86 CD68 Finally, they overexpression behavior could blocked inhibiting show centrally GATA1's behavior.This provides take home messages: (1) Peripheral responses, neutrophil, lymphocyte platelet counts, valuable predictors allow identification developing (2) Lipoxygenases, post-ischemic damage NLRP-1 -3-dependent activation. (3) decreases GLT1 GLAST astrocytes, evokes neuronal-astrocyte co-cultures. (4) behavior. Together, papers emphasize interplay diverse types (neurons, microglia, leukocytes) degenerating brain, maintain injury, most notably membrane structures, disturb integrity function. With respect processes, share surprisingly large number mechanisms. if treatments suitable one area similar application another one. foster translation psychiatry fields.

Language: Английский

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