CCL11 or Eotaxin-1: An Immune Marker for Ageing and Accelerated Ageing in Neuro-psychiatric Disorders

Abstract

Background: CCL11 (eotaxin) is a chemokine with an important role in allergic conditions. Recent evidence indicates that CCL11 plays a role in brain disorders as well. Aims: This paper reviews the associations between CCL11 and aging, neurodegenerative, neuroinflammatory and neuropsychiatric disorders.Methods: Electronic databases were searched for original articles examining CCL11 in neuropsychiatric disorders.Results: CCL11 is rapidly transported from the blood to the brain through the brain-blood barrier. Age-related increases in CCL11 are associated with cognitive impairments in executive functions, episodic and semantic memory and, therefore, this chemokine was described as an “endogenous cognition deteriorating chemokine” (ECDC) or “accelerated brain-aging chemokine” (ABAC). In schizophrenia, increased CCL11 is not only associated with impairments in cognitive functions, but also with key symptoms including formal thought disorders. Some patients with mood disorders and premenstrual syndrome show increased plasma CCL11 levels. In diseases of old age, CCL11 is associated with lowered neurogenesis and neurodegenerative processes and, as a consequence, increased CCL11 increases risk towards Alzheimer's Disease. Polymorphisms in the CCL11 gene are associated with stroke. Increased CCL11 also plays a role in neuroinflammatory disease including multiple sclerosis. In animal models, neutralization of CCL11 may protect against nigrostriatal neurodegeneration. Increased production of CCL11 may be attenuated by glucocorticoids, minocycline, resveratrol and anti-CCL11 antibodies.Conclusion: Increased CCL11 production during inflammatory conditions may play a role in human disease including age-related cognitive decline, schizophrenia, mood disorders and neurodegenerative disorders. Increased CCL11 production is a new drug target in the treatment and prevention of those disorders.

Understanding the action mechanisms of metformin in the gastrointestinal tract

“…Persistent mild inflammation and changes in the immune system are characteristic features of the aging process and diseases associated with old age (Franceschi et al, 2018;Aiello et al, 2019). Studies suggest that metformin could impact the longevity of mice and C. elegans by regulating the mTOR signaling pathway and suppressing the release of CCL11 cytokines, which are connected to age-related cellular and tissue impairments (Thakkar et al, 2013;Bannister et al, 2014;Wu et al, 2016;Howell et al, 2017;Ivanovska et al, 2020). Surprisingly, metformin prolonged the lifespan of mammals and decreased lung inflammation caused by COVID-19 in a mouse model of acute respiratory distress, possibly by blocking the activation of NLRP3 inflammasome through the inhibition of mitochondrial DNA synthesis (Xian et al, 2021).…”

Spotlight on pro-inflammatory chemokines: regulators of cellular communication in cognitive impairment

“…Activated astrocytes or BBB crossover sources release CCL11, while activated microglia express CCR3 ( 105 ). CCL11 binding to microglia-expressed CCR3 up-regulates nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX-1), promotes the production of ROS by microglia, which induces inflammation and neuronal cytotoxicity leading to neuronal cell death ( 110 , 111 ).…”

“…It is elevated in the serum of AD patients but not altered in the cerebrospinal fluid (CSF) ( 114 , 115 ). However, less is known about its involvement in the pathogenesis of AD ( 111 ). The main pathogenesis of AD is the degeneration of neurons in the hippocampal gyrus and the cerebral cortex, with the hippocampal region playing a crucial role in learning and memory processes.…”

“…CCR3, which is present in microglia, is more highly expressed in reactive microglia in AD patients. Knockdown of CCR3 in mice reduces synaptic loss and improves memory deficits and spatial learning, further suggesting that CCL11 may increase the risk of AD ( 111 ).…”

In Schizophrenia, Depression and Anxiety Symptoms Are Driven by Immune-Inflammatory Pathways.

“…In humans, CCL11 acts as an "endogenous cognitive deteriorating chemokine (ECDC)" or an "accelerated brain ageing chemokine (ABAC)" (Sirivichayakul et al, 2019) by decreasing hippocampal neurogenesis and impairing hippocampal learning and memory (Villeda et al, 2011). This chemokine is not only increased in schizophrenia (Sirivichayakul et al, 2019;Ivanovska et al, 2020), but also in affective disorders (Simon et al, 2008;Grassi-Oliveira et al, 2012;Magalhaes et al, 2014;Teixeira et al, 2018).…”