IL-17A drives cognitive aging probably via inducing neuroinflammation and theta oscillation disruption in the hippocampus.

Cognitive aging is a major risk factor for neurodegenerative diseases and has a great impact on the living quality of older individuals. However, the precise mechanisms underlying cognitive aging remain elusive. Accumulating evidence has demonstrated that interleukin 17A (IL-17A) is responsible for cognitive decline in the process of various neurological diseases. Thus, we conducted this study aiming to investigate the role of IL-17A in cognitive aging. In the present study, 31 aging (65-85 years) and 25 young (18-35 years) patients scheduled for elective removal of internal fixation surgery with spinal anesthesia were included for measurements of preoperative cognitive function, serum and cerebrospinal fluid (CSF) levels of IL-17A. For animal study, RNAseq and Kyoto Encyclopedia of Genes and Genomes pathways were used to identify differentially expressed genes between young and aging mice. For the treatment groups, young (2-3 months) and aging (16-18 months) mice received intraperitoneally with IL-17A and anti-IL-17A antibody, respectively. Twenty-four hours later, neurocognitive behavioral tests were conducted. Our results suggested that differentially expressed genes between young and aging mice were mainly enriched in IL-17 pathways. Serum and CSF levels of IL-17A increased significantly in aging patients and were negatively correlated with mini-mental state examination scores. Both young mice receiving IL-17A and aging mice showed impaired memory, increased blood-brain barrier permeability, overactivated microglia and increased inflammatory mediators in the hippocampus. Additionally, aging mice showed a significantly decreased θ power in the task-related neural oscillations. Notably, intraperitoneal injection of anti-IL-17A antibody alleviated increased blood-brain barrier permeability, microglial activation, neuroinflammation, θ oscillation disruption and cognitive decline of aging mice. In conclusion, our study demonstrated that IL-17A may be an initiating factor of cognitive aging.

• Publication year

  2022

• Venue

  International Immunopharmacology

• Publication date

  2022-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.intimp.2022.108898PMID 35729833
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Principles of brain aging: Status and challenges of modeling human molecular changes in mice.

  2021cited by this paper
• Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice

  2021cited by this paper
• Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions

  2021cited by this paper
• Disentangling neocortical alpha/beta and hippocampal theta/gamma oscillations in human episodic memory formation

  2021cited by this paper
• Susceptibility of aging mice to listeriosis: Role of anti-inflammatory responses with enhanced Treg-cell expression of CD39/CD73 and Th-17 cells.

  2020cited by this paper
• IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer's disease.

  2020cited by this paper
• A review of theta oscillation and its functional correlates.

  2020cited by this paper
• Interleukin-17A: The Key Cytokine in Neurodegenerative Diseases

  2020cited by this paper
• The IL-17 Family of Cytokines in Health and Disease.

  2019cited by this paper
• IL-17a promotes sociability in mouse models for neurodevelopmental disorders

  2019cited by this paper
• IL-17A contributes to perioperative neurocognitive disorders through blood-brain barrier disruption in aged mice

  2018cited by this paper
• Age-related cognitive impairment is associated with long-term neuroinflammation and oxidative stress in a mouse model of episodic systemic inflammation

  2018cited by this paper
• Imbalance of Circulating Th17 and Regulatory T Cells in Alzheimer’s Disease: A Case Control Study

  2018cited by this paper
• Molecular and cellular aspects of age‐related cognitive decline and Alzheimer's disease

  2017cited by this paper
• Interleukin 17 is a chief orchestrator of immunity

  2017cited by this paper
• Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers

  2016cited by this paper
• IL-17A and Multiple Sclerosis: Signaling Pathways, Producing Cells and Target Cells in the Central Nervous System.

  2016cited by this paper
• The effect of aging on brain barriers and the consequences for Alzheimer’s disease development

  2016cited by this paper
• Neuronal network activity in the hippocampus of tau transgenic (Tg4510) mice.

  2016cited by this paper
• Blood-brain barrier breakdown in the aging human hippocampus.

  2015cited by this paper
• Cognitive aging: a report from the Institute of Medicine.

  2015cited by this paper
• Neural Oscillations and Synchrony in Brain Dysfunction and Neuropsychiatric Disorders: It's About Time.

  2015cited by this paper
• Successful execution of working memory linked to synchronized high-frequency gamma oscillations.

  2014cited by this paper
• Microglia development and function.

  2014cited by this paper
• Increased Serum Levels of Interleukin-18, -23 and -17 in Chinese Patients with Alzheimer's Disease

  2014cited by this paper
• The global prevalence of dementia: A systematic review and metaanalysis

  2013cited by this paper
• Normal cognitive aging.

  2013cited by this paper
• Brain oscillations in neuropsychiatric disease

  2013cited by this paper
• Understanding how we age: insights into inflammaging

  2013cited by this paper
• Microglia: actively surveying and shaping neuronal circuit structure and function.

  2013cited by this paper
• IL-17 family: cytokines, receptors and signaling.

  2013cited by this paper
• The Th17/Treg balance is disturbed during aging.

  2013cited by this paper
• Age-dependent disruption in hippocampal θ oscillation in amyloid-β overproducing transgenic mice.

  2012cited by this paper
• Novel CSF biomarkers for frontotemporal lobar degenerations

  2010cited by this paper
• Aging, imbalanced inflammation and viral infection

  2010cited by this paper
• Aging promotes neutrophil-induced mortality by augmenting IL-17 production during viral infection.

  2009cited by this paper
• The role of oscillations and synchrony in cortical networks and their putative relevance for the pathophysiology of schizophrenia.

  2008cited by this paper

• Mechanisms of Cognitive Aging: Health and Pathology

  2026cites this paper
• Weathering the Storm: How Age and Biologics Influence the COVID-19 Cytokine Surge

  2025cites this paper
• The brain-gut microbiota network (BGMN) is correlated with symptom severity and neurocognition in patients with schizophrenia

  2025cites this paper
• Linear association between high-sensitivity C-reactive protein and postoperative delirium after general anesthesia: a cross-sectional study

  2025cites this paper
• Ginseng in delaying brain aging: Progress and Perspectives.

  2025cites this paper
• Hydroxysafflor Yellow A Reduced Neuroinflammation Induced by Astrocyte-Derived IL-17A by Inhibiting the IL-17RA/ACT1/NF-κB/IL-17A Loop After OGD/R

  2025cites this paper
• A new perspective on cognitive impairment in major depressive disorder: Changes in gut microbiota and their inflammatory regulatory mechanisms.

  2025cites this paper
• The Role of T Cells in Alzheimer's Disease.

  2025cites this paper
• IL-17A is a key regulator of neuroinflammation and neurodevelopment in cognitive impairment induced by sevoflurane.

  2024cites this paper
• Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

  2024cites this paper
• T Cells Trafficking into the Brain in Aging and Alzheimer’s Disease

  2024cites this paper
• Bidirectional interaction between IL and 17A/IL-17RA pathway dysregulation and α-synuclein in the pathogenesis of Parkinson's disease.

  2024cites this paper
• The impact of neuroinflammation on neuronal integrity

  2024cites this paper
• Androgen Deprivation Therapy for Prostate Cancer: Focus on Cognitive Function and Mood

  2023cites this paper
• Long-term intermittent theta burst stimulation enhanced hippocampus-dependent memory by regulating hippocampal theta oscillation and neurotransmitter levels in healthy rats.

  2023cites this paper
• Physiological roles of human interleukin‐17 family

  2023cites this paper
• Alteration of Cognitive Function in Aging and Alzheimer’s Disease Mice Is Related to Dysfunction of the Neuroimmune System

  2023cites this paper
• Th17 cells and inflammation in neurological disorders: Possible mechanisms of action

  2022cites this paper