Brain Interleukin-1 Facilitates Learning of a Water Maze Spatial Memory Task in Young Mice

Expert opinion

Cytokines can be considered as the hormones of the immune system. Produced in response to different stimuli, polypeptide molecules are involved in regulation of immune functions, as well as in hematopoiesis and hemostasis. Cytokines are key mediators of inflammatory responses following exposure to pathogens, triggering a cascade of events that involves many immune cell-types.
Recent studies have revealed new roles of cytokines in chronic disorders of the central nervous system, such as depression, and in neurodegenerative conditions such as Alzheimer’s disease, leading to neuronal dysfunction and cell death.
The word “cytokine” is tightly linked with “inflammation”. Do some cytokines have other physiological functions? The answer is “yes”, which is exactly what Takako Takemiya investigated and described thoroughly in this very interesting article.
She studied the learning capabilities of mice, both young and adult, wild-type and knockout (KO) for IL-1β or IL-1 receptor (IL-1R), using a water maze spatial memory task model.
Following trial phases and learning experiments with these different mice populations, she quantified the level of production of IL-1β and IL-1αextracted directly from the hippocampus or the cortex of mice brains. She proved that water maze spatial learning and the memory task were impaired significantly in young IL-1βKO and IL-1R KO, but not in adult KO mice.
Further investigation of the exact role of IL-1βin cortical and hippocampal neurons, at different stages of development from young to adult, will help elucidate the molecular mechanisms and pathways involved in this mechanism of learning. However, pro-inflammatory IL-1βcytokine seems to have broader functions than that classically described in inflammation processes.
It’s time to understand new functions for cytokines and new possibilities for therapeutic treatments of central nervous system impairments or disorders

Abstract

The proinflammatory cytokine interleukin-1 (IL-1) is produced by many types of cells, including immune cells in the periphery and glia and neurons in the brain. The type I IL-1 receptor (IL-1r1) is primarily responsible for transmitting the inflammatory effects of IL-1 and mediates several biological functions by binding to either IL-1α or IL-1β. IL-1β activation is associated with hippocampus-dependent memory tasks. Although IL-1β impairs spatial memory under certain pathophysiological conditions, IL-1β may be required for the normal physiological regulation of hippocampal plasticity and memory. In addition, brain IL-1β levels are thought to change in the hippocampus in an age-dependent manner. These findings suggest that IL-1β may have a beneficial, temporary effect on learning and memory in young mice, but the matter remains unclear. Therefore, we hypothesized that hippocampal IL-1β has a beneficial effect on spatial learning and memory in young mice via IL-1r1, which is diminished in adults. We investigated the performance of young (3-month-old) and adult (6-month-old) wild-type mice, IL-1β knockout mice (IL-1βko) and IL-1r1 knockout mice (IL-1r1ko) in learning a spatial memory task with a fixed platform in a water maze (WM) and measured the levels of IL-1β and IL-1α in the hippocampus and cortex of adult and young mice by using homogeneous time-resolved fluorescence (HTRF). Learning was significantly impaired in the training trials of the WM spatial memory task in young IL-1βko and IL-1r1ko mice but not in adult IL-1βko and IL-1r1ko mice. Moreover, young IL-1r1ko mice but not IL-1βko mice showed an impairment in long-term memory extinction, suggesting that IL-1α might facilitate memory extinction. In this study, the cytokine assay using HTRF did not indicate a higher expression of hippocampal IL-1 in young mice but cortical IL-1β and IL-1α were significantly increased in adult mice. We need to investigate the role of cortical IL-1 and the local IL-1 expression in the hippocampal neurons in the future.