Hyperactive Type I Interferon System in the Choroid Plexus Linked To Aging and Cognitive Dysfunction
A study published in the August 21, 2014 issue of Science magazine demonstrates that aging is associated with an overactive interferon (IFN)-I system at a specific brain structure, the choroid plexus.
This vascular tissue, found in all cerebral ventricles, is an epithelial monolayer that forms the blood-cerebrospinal fluid barrier, and, in fact, represents the ‘interface’ between the brain and the circulation.
Interferons are large group of proteins, discovered in 1957, and mostly involved in the protection against viral infections.
Previous research indicates a link between the overproduction of type I interferons (IFN-I) in the central nervous system (CNS) and memory impairments in several neuro-inflammatory human diseases. In addition, neurological and neuropsychiatric complications are often reported in patients with hepatitis C and cancer, treated with IFN-α.
In the Science study, Kuti Baruch and colleagues from the Weizmann Institute of Science, Rehovot, Israel found that brain sections of mice or postmortem brain sections from non-CNS-diseased humans had aging-associated over-expression of IFN-I at the choroid plexus, and this was driven by signals from the brain, present in the cerebrospinal fluid.
Of note, the authors also showed that treatment of epithelial cells from the choroid plexus with IFN-β (key member of the IFN-I family of cytokines) suppressed the expression of insulin-like growth factor (igf1) and brain derived neurotrophic factor (bdnf), molecules that are essential for neuronal growth and survival.
Importantly, administration of neutralizing antibodies to the IFN-I receptor (α-IFNAR), counter-acted IFN-I signaling within the brain which allowed cognitive function to be restored in aged mice. Noteworthy, this was accompanied by an enhanced hippocampal neurogenesis and expression of the anti-inflammatory cytokine interleukin-10, and a decrease in astrogliosis and microgliosis.
Thus, besides the new important research insights, the study suggests that neutralizing type I IFNs response within the CNS may provide new therapeutic target or approach to control or prevent age-associated cognitive decline.
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also discussed at: Neuroendocrine Immunology in 2014